Hematological indices and the prevalence of anemia in an elderly Chinese population

Hematological indices were determined in a group of 427 elderly Chinese subjects over 60 years old; reference ranges were established after excluding subjects with hemoglobinopathies or diseases giving rise to anemia and those with values less or greater than 3 SD from the mean. The values were similar to those for elderly Caucasians. All the red cell indices were significantly higher in men than women, possibly reflecting the influence of androgens on bone marrow function. Previously reported age-related decline in hemoglobin, red cell count and hematocrit from studies of all age groups was not seen in men or women above age 60 years, but a fall in platelet count with age, which had not been previously reported, was observed. There were no age-related changes in any other indices. Reference ranges were lower for Hb, MCV, and MCH in men and women, compared to those derived from a study of Chinese of all age groups. The prevalence of anemia due to disease and hemoglobinpathies in this population was 6.4% in men and 6.3% in women.     

Biological characterization of a novel biodegradable antimicrobial polymer synthesized with fluoroquinolones.

Biomaterial-related infections continue to represent a significant challenge to the medical community. Several approaches have been utilized to incorporate antimicrobial agents at the surface of implant devices in attempts to delay or eliminate the formation of biofilms. To date, most of these strategies have focused on drug conjugation or diffusion-limited systems for the delivery of such pharmaceutical agents. More recently, work has been presented on the feasibility of incorporating drugs into the backbone of polymers as a main-chain monomer. When sequenced into the backbone of the polymer with other monomers that are hydrolytically sensitive to enzyme-catalyzed breakdown, it is thought that drugs may be able to be selectively released. Specifically, degradable polyurethanes have been synthesized with fluoroquinolone antibiotics and have shown an ability to kill bacteria when released following degradation of the polymer chains by the macrophage-derived enzyme cholesterol esterase. However, specificity of the cleavage sites in the polymer was difficult to control. Since cholesterol esterase has specificity for hydrophobic moieties, it is desirable to alter the formulation of the polyurethanes to incorporate long hydrophobic monomers immediately adjacent to the ciprofloxacin molecule. Hence, the current study focuses on evaluating the enzyme-catalyzed degradation of a degradable polyurethane synthesized with 1,12 diisocyanatododecane as a substitute for 1,6 diisocyanatohexane, which was used in previous work. Validation of specific ciprofloxacin release and the generation of antimicrobial are shown. A preliminary cell study to assess the cytotoxicity of this biodegradable antibiotic polymer shows that the material has no observable effects on cell proliferation or cell membrane structure.     

A novel lysophospholipid- and pH-sensitive receptor, GPR4, in brain endothelial cells regulates monocyte transmigration.

Abundant evidence documents the highly proinflammatory actions of lysophosphatidylcholine (LPC). Further, LPC, found in high amounts in oxidized low-density lipoprotein (LDL), is implicated as an atherogenic factor. In endothelial cells, LPC impairs endothelial barrier function through GPR4, a novel receptor hypothesized to be sensitive to LPC and protons. The authors investigated the stimulation by LPC or low pH of GPR4 in human brain microvascular endothelial cells (HBMECs) and whether the activated GPR4 regulates in vitro monocyte transmigration. The results indicated that HBMECs stimulated by LPC (5 microM), but not low pH, showed a twofold increase in monocyte transmigration. Using retroviruses containing siRNA to GPR4, a > 60% reduction of GPR4 expression resulted in blockade of the LPC-stimulated transmigration. The inhibited response was restored by co-expression with an small interference RNA (siRNA)-resistant, but functional, GPR4 mutant construct. To investigate potential signaling mechanisms, the siRNA-mediated knockdown of GPR4 also prevented LPC-induced RhoA activation. C3 transferase, a Rho inhibitor, prevented approximately approximately 65% of the LPC-stimulated transmigration. LPC also increased MLC phosphorylation by 5 min, which was inhibited by the Rho kinase inhibitor, Y-27632 (10 microM) or ML-7 (myosin light chain kinase (MLCK) inhibitor). The findings indicate that the proinflammatory and atherogenic LPC stimulated endothelial GPR4, which promoted monocyte transmigration through a RhoA-dependent pathway.     

Hepatic and small bowel mucormycosis after chemotherapy in a patient with acute lymphocytic leukemia

Mucormycosis is a rare but invasive opportunistic fungal infection with increased frequency during chemotherapy-induced neutropenia. The clinical infections due to Mucor include rhinocerebral, pulmonary, cutaneous, gastrointestinal and disseminated diseases. The first two are the most common diseases and all entities are associated with a high mortality rate. Still hepatic involvement of Mucor is rarely reported. We experienced a case of hepatic and small bowel mucormycosis in a 56-year-old woman after induction chemotherapy for B-cell acute lymphocytic leukemia. Initial symptoms were a high fever unresponsive to broad spectrum antibiotics and pain in the left lower abdominal quadrant. It was followed by septic shock, deterioration of icterus and progressively elevated transaminase. An abdominal CT demonstrated multiple hypodense lesions with distinct margins in both lobes of liver and pericolic infiltration at small bowel and ascending colon. Diagnosis was confirmed by biopsy of the liver. The histopathology of the liver showed hyphae with the right-angle branching, typical of mucormycosis. The patient was managed with amphotericin B and operative correction of the perforated part of the small bowel was performed. However, the patient expired due to progressive hepatic failure despite corrective surgery and long-term amphotericin B therapy.     

A case of multiple schwannomas of the trigeminal nerves, acoustic nerves, lower cranial nerves, brachial plexuses and spinal canal: schwannomatosis or neurofibromatosis?

In most cases, while schwannoma is sporadically manifested as a single benign neoplasm, the presence of multiple schwannomas in one patient is usually indicative of neurofibromatosis 2. However, several recent reports have suggested that schwannomatosis itself may also be a distinct clinical entity. This study examines an extremely rare case of probable schwannomatosis associated with intracranial, intraspinal and peripheral involvements. A 63-year-old woman presented with a seven-year history of palpable lumps on both sides of the supraclavicular area and hearing impairment in both ears. On physical examination, no skin manifestations were evident. Facial sensory change, deafness in the left ear and decreased gag reflex were revealed by neurological examination. Magnetic resonance imaging revealed multiple lesions of the trigeminal nerves, acoustic nerves, lower cranial nerves, spinal accessory nerve, brachial plexuses, and spinal nerves. Pathological examination of tumors from the bilateral brachial plexuses, the spinal nerve in the T8 spinal position and the neck mass revealed benign schwannomas. Following is this patient case report of multiple schwannomas presenting with no skin manifestations of neurofibromatosis.     

Chemical, structural properties, and osteoconductive effectiveness of bone block derived from porcine cancellous bone

The purpose of this study is to determine the efficacy of bioactive calcium phosphate obtained from porcine cancellous bone for the treatment of bone defects and nonunion. Porcine cancellous bone blocks were heat treated at 1300 degrees C for 2 h. The chemical composition, calcium-to-phosphate ratio, and microstructure of the porcine bone blocks were examined. For in vivo implantation, bone defects were created on the anteromedial aspect of the proximal tibia in seven beagle dogs and the xenograft bone blocks were placed into these defects. Plain radiographs were taken at 2-week intervals for roentgenographic evaluation. At 12 weeks, the specimens were stained with hematoxylin and eosin (H&E). The composition and morphology of heat-treated porcine cancellous bone were found to be similar to heat-treated human cancellous bone. Radiographs showed union between the host bone/bone-block interfaces. At 12 weeks, uniform and substantial new bone formation was observed. It is concluded that heat-treated porcine cancellous bone demonstrated effective osteoconductivity. This high-temperature heat-treatment technique has several advantages, including decreased risk of disease transmission and immunoreactivity, while also offering excellent biocompatibility.     

Differential sensitivities of severe acute respiratory syndrome (SARS) coronavirus spike polypeptide enzyme-linked immunosorbent assay (ELISA) and SARS coronavirus nucleocapsid protein ELISA for serodiagnosis of SARS coronavirus pneumonia

The use of recombinant severe acute respiratory syndrome-coronavirus (SARS-CoV) nucleocapsid protein (N) enzyme-linked immunosorbent assay (ELISA)-based antibody and antigen tests for diagnosis of SARS-CoV infections have been widely reported. However, no recombinant SARS-CoV spike protein (S)-based ELISA is currently available. In this article, we describe the problems and solutions of setting up the recombinant SARS-CoV S-based ELISA for antibody detection. The SARS-CoV S-based immunoglobulin M (IgM) and IgG ELISAs were evaluated and compared with the corresponding N-based ELISA for serodiagnosis of SARS-CoV pneumonia, using sera from 148 healthy blood donors who donated blood 3 years ago as controls and 95 SARS-CoV pneumonia patients in Hong Kong. Results obtained by the recombinant S (rS)-based IgG ELISA using the regenerated S prepared by dialysis with decreasing concentrations of urea or direct addition of different coating buffers, followed by addition of different regeneration buffer, identified 4 M urea and 1 M sarcosine for plate coating and no regeneration buffer as the most optimal conditions for antibody detection. The specificities of the S-based ELISA for IgG and IgM detection were 98.6% and 93.9%, with corresponding sensitivities of 58.9% and 74.7%, respectively. The sensitivity of the rN IgG ELISA (94.7%) is significantly higher than that of the rS IgG ELISA (P < 0.001), whereas the sensitivity of the rS IgM ELISA is significantly higher than that of the rN IgM ELISA (55.2%) (P < 0.01). An ELISA for detection of IgM against S and N could be more sensitive than one that detects IgM against N alone for serodiagnosis of SARS-CoV pneumonia.     

Spontaneous acute tumor lysis syndrome with advanced gastric cancer

Acute tumor lysis syndrome (TLS) occurs frequently in hematologic malignancies such as high-grade lymphomas and acute leukemia, which are rapidly proliferating and chemosensitive tumors. It occurs rarely in solid tumors and has never been reported in gastric adenocarcinoma. Typical biochemical findings of acute tumor lysis syndrome are hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia in patients with a malignancy. Rapid changes of these electrolytes may cause cardiac arrhythmia, seizure, acute renal failure and sudden death. Therefore, as soon as it is detected, it should be taken care of immediately. Until now almost all cases of TLS associated with solid tumor have developed after cytoreductive therapy in chemosensitive tumors. We report here a case of spontaneous acute tumor lysis in a patient of advanced gastric cancer with hepatic metastases and multiple lymphadenopathy. The biochemical finding of TLS improved with the management and tumor burden also showed slight response to the one cycled combination chemotherapy but the patient died of progressive pneumonia.     

Myopathic alterations in extraocular muscle of rats subchronically fed pyridostigmine bromide

To determine if alterations in extraocular muscle morphology occur after subchronic oral administration of pyridostigmine bromide, rats were continuously fed 90 mg/kg in meal and examined at 1, 2, 4, 7, and 15 days. Within the first day, blood acetylcholinesterase activity was reduced by 87% and remained inhibited by 74-91% during the study. Light microscopy demonstrated that by day 1 approximately 3% of the extraocular myofibers were shrunken and invaded by inflammatory cells. The most severe degenerative changes consisting of vacuoles and inflammatory cell infiltration occurred at day 1 with progressively less severe changes at days 2 and 4. At days 7 and 15, 1.3-4.5% of the myofibers still exhibited damage. Ultrastructurally, all presynaptic areas were normal but the postsynaptic areas of affected myofibers at days 1, 2, and 4 showed myofilament and Z-band dissolution, mitochondrial inclusions, subneural fold and T-tubule/sarcoplasmic reticulum vacuolization and subneural fold depth reduction. By days 7 and 15, these changes were diminished in some cases and in others alterations appeared similar to day 1. We conclude that subchronic feeding of pyridostigmine bromide induces myopathic rather than neurogenic changes in rat extraocular muscle and that the myopathy is different in these muscles than in the diaphragm from the the same rats.     

Brain responses associated with the Valsalva maneuver revealed by functional magnetic resonance imaging

The Valsalva maneuver, a test frequently used to evaluate autonomic function, recruits discrete neural sites. The time courses of neural recruitment relative to accompanying cardiovascular and breathing patterns are unknown. We examined functional magnetic resonance imaging signal changes within the brain to repeated Valsalva maneuvers and correlated these changes with physiological trends. In 12 healthy subjects (age, 30-58 yr), a series of 25 volumes (20 gradient echo echo-planar image slices per volume) was collected using a 1.5-Tesla scanner during a 60-s baseline and 90-s challenge period consisting of three Valsalva maneuvers. Regions of interest were examined for signal intensity changes over baseline and challenge conditions in cardiorespiratory-related regions. In addition, whole brain correlations between signal intensity and heart rate and airway load pressure were performed on a voxel-by-voxel basis. Significant signal changes, correlated with the time course of load pressure and heart rate, emerged within multiple areas, including the amygdala and hippocampus, insular and lateral frontal cortices, dorsal pons, dorsal medulla, lentiform nucleus, and fastigial and dentate nuclei of the cerebellum. Signal intensities peaked early in the Valsalva maneuver within the hippocampus and amygdala, later within the dorsal medulla, pons and midbrain, and deep cerebellar nuclei, and last within the lentiform nuclei and the lateral prefrontal cortex. The ventral pontine signals increased during the challenge, but not in a fashion correlated to load pressure or heart rate. Sites showing little or no correlation included the vermis and medial prefrontal cortex. These data suggest an initiating component arising in rostral brain areas, a later contribution from cerebellar nuclei, basal ganglia, and lateral prefrontal cortex, and a role for the ventral pons in mediating longer term processes.