Multiple splenic infarctions in a dog with immune-mediated hemolytic anemia: therapeutic implications.

BACKGROUND: Splenic infarction (SI) is a rare clinical entity seldom encountered in veterinary medicine. Its most frequent causes include thromboembolic status, splenomegaly, and cardiac disease. Although thrombotic elements from the circulation provide the most common context for thromboembolic SIs, immune-mediated hemolytic anemia (IMHA) has not been reported as an underlying disease in canine SI. CASE DESCRIPTION: A 2-year-old, female spayed Dachshund, was referred with vomiting, hematochezia, and brown colored urine over the preceding 4 days. Physical examination revealed abnormalities including generalized weakness, jaundice, and splenomegaly; blood work showed pancytopenia and hyperbilirubinemia. Erythrocyte agglutination, polychromasia, and spherocytes on a peripheral blood smear were observed and IMHA concurrent with thrombocytopenia was diagnosed. FINDINGS/TREATMENT AND OUTCOME: Although erythrocyte agglutination and leukopenia disappeared after treatment, anemia and thrombocytopenia were unresponsive to oral immunosuppressive drugs and repeated transfusions. Further abdominal ultrasound identified an occlusive splenic vein thrombus. Splenic histopathology found marked multifocal to coalescing necrosis, and hemorrhage consistent with multiple SI. Symptoms resolved following splenectomy combined with 1 month of immunosuppressive medication, and the dog was healthy on follow-up evaluation after 2 years. CONCLUSION: Immune-mediated hemolytic anemia is an incompletely characterized cause of SI. This report establishes a potential and novel causal role for IMHA in canine SI. We believe it to be the first case report of SI in a dog with refractory IMHA and thrombocytopenia, successfully managed by splenectomy combined with short-term immunosuppressive therapy.

Anomalous muscles and nerves in the hand of a 94-year-old cadaver-A case report.

INTRODUCTION: During an anatomical dissection of the distal upper extremities, numerous muscular and nervous anomalies were found in the forearm and hand of a 94-year-old cadaver. These anomalies are clinically relevant with regard to medical or surgical interventions. PRESENTATION OF CASE: The presence of a "flexor digiti minimi longus" muscle was observed passing through Guyon's canal; to our knowledge this passageway has never been previously reported. An aberrant first lumbrical with three origins was noted. Additionally, numerous atypical nerves were found innervating the hand; the dorsal branch of the ulnar nerve contributed to cutaneous innervation of the palm of the hand (Kaplan's anastomosis), the superficial ulnar nerve provided muscular innervation to the flexor digiti minimi brevis muscle, and two connections between the common palmar digital branches of the median and superficial ulnar nerves were observed (Berrettini anastomosis). DISCUSSION: Here, we describe an extranumerary muscle associated with the hypothenar group of muscles. We also describe unusual origins of the first lumbrical muscle, and atypical cutaneous and muscular innervation to the palm of the hand. CONCLUSION: Clinically, understanding the existence of these anatomical variations may influence medical care or surgical procedures.

Chemical and genetic diversity of high-seed-yield sorghum (Sorghum bicolor M.) germplasms.

This study evaluated the chemical and genetic diversity of high-seed-yield sorghum germplasms from Korea, the United States, and South Africa. We identified significant differences in the chemical contents of whole plants at the heading stage in all cultivars, including differences in crude protein, fat, fiber, ash, neutral detergent fiber, acid detergent fiber, mineral, and fatty acid contents. Our results suggest that Banwoldang is the most appropriate cultivar for roughage because of its high protein yield. We identified significant differences in the tannin, flavonoid, amylose, mineral, crude fat, fatty acid, and 3-deoxyanthocyanin contents in the whole grain from all cultivars, but not in the mineral or crude fat contents. Tannin levels were generally low. IS645 contained the highest levels of flavonoids and linolenic acid compounds, and Moktak had the highest amylose and deoxyanthocyanidin content in the grain. To assess genetic diversity, we used 10 simple sequence repeat (SSR) primer sets to identify 38 alleles with 3-8 alleles per locus. Based on phylogenetic analysis of the SSR markers, the sorghum cultivars were divided into three major groups. Comparison of clusters based on chemical compositions with those based on SSRs showed that the groups formed by the three native Korean cultivars clustered similarly in molecular dendrograms. Association analysis was conducted for the 10 SSR marker; 48 chemical and growth traits were present for two marker traits (seed color and whole plant fatty acid content) with significant marker-trait associations. These markers could be used to select sorghum cultivars for breeding programs.

Development of a transposon-based marker system for mutation breeding in sorghum (Sorghum bicolor L.).

Under certain circumstances, transposable elements (TE) can create or reverse mutations and alter the genome size of a cell. Sorghum (Sorghum bicolor L.) is promising for plant transposon tagging due to its small genome size and its low content of repetitive DNA. We developed a marker system based on targeted region amplification polymorphisms (TE-TRAP) that uses the terminal inverted repeats (TIRs) of transposons. A total of 3816 class 2 transposons belonging to the PIF/Harbinger family were identified from the whole sorghum genome that produced five primers, including eight types of TIRs. To define the applicability and utilization of TE-TRAP, we used 21 individuals that had been bred after ɤ-ray irradiation. In total, 31 TE-TRAP, 16 TD, and 21 AFLP primer combinations generated 1133, 223, and 555 amplicons, respectively. The percent polymorphic marker was 62.8, 51.1, and 59.3% for the TE-TRAP, TD, and AFLP markers, respectively. Phylogenetic and principal component analyses revealed that TE-TRAP divided the 21 individuals into three groups. Analysis of molecular variance suggested that TE-TRAP had a higher level of genetic diversity than the other two marker systems. After verifying the efficiency of TE-TRAP, 189 sorghum individuals were used to investigate the associations between the markers and the ɤ-ray doses. Two significant associations were found among the polymorphic markers. This TE-based method provides a useful marker resource for mutation breeding research.

Effects of age, replicative lifespan and growth rate of human nucleus pulposus cells on selecting age range for cell-based biological therapies for degenerative disc diseases.

Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases.

Relative adrenal insufficiency in chronic liver disease: its prevalence and effects on long-term mortality.

BACKGROUND: The relationship between relative adrenal insufficiency (RAI) and chronic liver disease is unclear. AIM: To determine the frequency with which RAI is observed in noncritically ill patients at various stages of chronic liver disease, and the correlation between RAI and disease severity and long-term mortality. METHODS: In total, 71 non-critically ill patients with liver cirrhosis (n = 54) and chronic hepatitis (n = 17) were evaluated prospectively. A short stimulation test (SST) with 250 µg of corticotrophin was performed to detect RAI. RAI was defined as an increase in serum cortisol of <9 µg/dL in patients with a basal total cortisol of <35 µg/dL. RESULTS: RAI was observed in only 13 (24.1%) of 54 patients with cirrhosis. Compared to those without RAI, cirrhotic patients with RAI had significantly higher Child-Turcotte-Pugh score (10.3 ± 1.7 vs. 7.1 ± 1.8, mean ± s.d., P < 0.001) and Model for End-Stage Liver Disease score (14.5 ± 6.6 vs. 9.4 ± 3.7, P = 0.017). The cortisol response to corticotropin was negatively correlated with the severity of cirrhosis (P < 0.05). In addition, the mortality rate was higher in cirrhotic patients with RAI (69.2%) than in those without RAI (4.9%; P < 0.001) during the follow-up period of 20.1 ± 13.5 months (range, 5.8-51.1 months). The cumulative 1-year survival rates in cirrhotic patients with and without RAI were 69.2% and 95.0%, respectively (P = 0.05), while the corresponding cumulative 3-year survival rates were 0% and 95.0% (P < 0.001). CONCLUSIONS: Relative adrenal insufficiency is more commonly observed in those with severe cirrhosis, and is clearly associated with more advanced liver disease and a shortened long-term survival. This suggests that relative adrenal insufficiency is an independent prognostic factor in non-critically ill patients with cirrhosis.

The role of psychological distress in laryngopharyngeal reflux patients: a prospective questionnaire study.

OBJECTIVES: To determine the role of psychological distress in laryngopharyngeal reflux patients and evaluate the correlation between symptoms, laryngeal signs, pH monitoring results and psychological profile. DESIGN: Prospective study. SETTING: Hanyang University Hospital, a university teaching hospital and tertiary referral center. PARTICIPANTS: One hundred and six patients who were diagnosed with laryngopharyngeal reflux by 24-h ambulatory double probe pH monitoring and 119 healthy controls visiting our health promotion center from January 2006 to June 2007. MAIN OUTCOME MEASURES: The psychological profile of laryngopharyngeal reflux patients measured by the Symptom Checklist-90-Revised questionnaire were evaluated and compared with those of healthy controls. The correlation between reflux symptom index, reflux finding score, parameters of pH monitoring and the Symptom Checklist-90-Revised profiles were also evaluated. RESULTS: On the Symptom Checklist-90-Revised questionnaire, the total mean T-scores of the nine symptom dimensions and three global indices of the laryngopharyngeal reflux patients were all below 50. The Global Severity Index, which indicates overall psychological distress, was normal in all of the patients. On comparison with the control group, no statistically significant difference was noted in the psychological profile except on the Somatisation scale where laryngopharyngeal reflux patients showed significantly higher scores. Reflux symptom index showed significant positive correlation with the number of reflux episodes, percentage of time which pH fell below 4 in total positions, and DeMeester score of the upper probe. The nine symptom dimensions and three global indices of Symptom Checklist-90-Revised questionnaire did not show any correlation with reflux symptom index, reflux finding score and the parameters of the 24-h ambulatory double probe pH monitoring. CONCLUSIONS: Laryngopharyngeal reflux patients did not demonstrate any significant level of psychological distress and their symptom severity showed significant positive correlation with reflux severity.

Phenylpropanolamine contained in cold remedies and risk of hemorrhagic stroke.

In this study, we sought to elucidate whether phenylpropanolamine (PPA) in cold remedies (small and divided doses) increases the risk of hemorrhagic stroke (HS). PPA exposure significantly increased the risk, and the risk was much higher in women. In women, linear trends were also found in recency, duration, and dosage of PPA exposure. PPA contained in cold remedies increases the risk of HS, particularly in women.

Comparative study between propofol in a long-chain triglyceride and propofol in a medium/long-chain triglyceride during sedation with target-controlled infusion.

This study was performed to compare the pharmacological characteristics of propofol in an emulsion of both medium- and long-chain triglycerides (MCT/LCT) with those of propofol in an LCT emulsion, by measuring the sedative level and the plasma concentration of propofol during sedation using a target-controlled infusion (TCI) technique. Forty ASA 1 or 2 adult patients who required spinal anaesthesia for surgery were enrolled in this study. The patients were divided into two groups: a propofol LCT group (n = 20) and a propofol MCT/LCT group (n = 20). Propofol was injected intravenously at target blood concentrations of 2.0, 3.0 and 4.0 microg x ml(-1). The bispectral (BIS) index was recorded, and arterial blood was drawn to measure the actual plasma concentrations of propofol at each predicted concentration. Propofol was assayed by high-performance liquid chromatography. Propofol MCT/LCT was associated with significantly less pain than propofol LCT (P < 0.05). There were no significant differences between the two groups in BIS index or in plasma concentration of propofol at each predicted concentration. Computer-generated TCI of propofol MCT/LCT during sedation is comparable with that of propofol LCT with respect to pharmacokinetics and pharmacodynamics. The formulation of MCT/LCT has a beneficial effect with respect to less pain on injection.

Functional and genetic assessment of IFN-gamma receptor in patients with clinical tuberculosis.

OBJECTIVE: The molecular basis of the genetic vulnerability underlying the most common form of clinical tuberculosis (TB) remains largely unknown. We speculated that mild genetic defects in the interferon-gamma (IFN-gamma) signalling pathway caused a subtle functional impairment of IFN-gamma which would explain susceptibility to Mycobacterium tuberculosis in clinical TB. DESIGN: A case-control study. RESULTS: We evaluated functional responsiveness to IFN-gamma in monocytes from patients with clinical TB (n = 10), and analysed the genetic sequences of the IFN-gamma receptor 1 (IFN-gammaR1) and STAT1 genes in patients with disseminated TB (n = 18). IFN-gamma stimulated an increase in the expression of HLA-DR and CD64 on monocytes of both controls and patients; the rate of increase in expression was the same in both groups. Treatment with IFN-gamma before lipopolysaccharide (LPS) stimulation further increased tumour necrosis factor-alpha (TNF-alpha) production as compared to TNF-alpha production with LPS stimulation alone; the rate of increase in TNF-alpha production was the same in both groups. The known mutations in the coding sequences of the IFN-gammaR1 and STAT1 genes were not found in the patients with disseminated tuberculosis. CONCLUSION: These results suggest that impairment of the IFN-gamma signalling pathway did not account for cases of clinical TB in this study.

Dicistronic expression of the green fluorescent protein and antibiotic resistance genes in the plastid for selection and tracking of plastid-transformed cells in tobacco.

A plastid transformation vector was constructed for dicistronic expression of the aminoglycoside 3'-adenyltransferase (aadA) and green fluorescent protein (gfp) genes under the control of the plastid rrn promoter. Gold particles coated with the vector DNA were bombarded onto tobacco leaf explants using a particle delivery system. Leaf explants produced adventitious shoots when cultured on shoot-inducing medium containing 500 mg l(-1) spectinomycin. Shoots that exhibited green fluorescence under UV light were selected. Southern blot analysis detected the presence of the aadA and gfp genes between trnA and trnI in the plastid genome. Northern blot analysis revealed that the aadA and gfp genes were both properly transcribed into a dicistronic transcriptional unit. The expression of the gfp gene in the plastid enabled separation of transformed chloroplasts from wild-type chloroplasts in the protoplast under a fluorescent microscope. The overall results indicate that dicistronic expression of the aadA and gfp genes in the plastid simplifies gene manipulation, facilitating selection and tracking of plastid-transformed cells.

Diffusion-weighted MR findings in isolated angiitis of the central nervous system (IACNS).

OBJECTIVES: To describe the diffusion-weighted MR (DWI) findings of isolated angiitis of the central nervous system (IACNS) and narrow the differential diagnosis. METHODS: The DWI findings of two IACNS patients. Apparent diffusion coefficient (ADC) values were measured in the abnormal lesions, and DWI and T2-weighted MR images were visually inspected. RESULTS: IACNS was diagnosed based on clinical history, MR findings and cerebral angiographic findings. DWI showed hyperintense lesions with heterogeneous ADC values (287-1359 x 10(-6) mm2/s), which indicate the coexistence of cytotoxic and vasogenic oedema. CONCLUSIONS: The findings suggest that the various stages of inflammatory process with ischaemia might exist in IACNS and allow a differentiation from the usual arterial ischaemic infarction. DWI with ADC map can be a useful non-invasive diagnostic test increasing specificity in the diagnosis of IACNS, combined with conventional MRI and cerebral angiography.

Antinociception of intrathecal cholinesterase inhibitors and cholinergic receptors in rats.

BACKGROUND: Intrathecal cholinesterase inhibitors have been shown to have an antinociceptive effect which is mediated through the spinal cholinergic receptors, mainly muscarinic receptor. Spinal nicotinic receptor also has been involved in the control of nociception. Authors characterized the respective role of muscarinic or nicotinic receptor for the antinociception of cholinesterase inhibitors and further determined the antinociceptive potency of them. METHODS: Rats were prepared with intrathecal catheters. Formalin-induced flinching response was regarded as a nociceptive behavior. RESULTS: Intrathecal neostigmine, physostigmine and edrophonium produced a dose-dependent suppression of flinching in both phases. Atropine and the M1 selective antagonist attenuated the effect of them, while the M2 selective antagonist did not affect. M3, M4 selective, and nicotinic receptor antagonists reversed the antinociception induced by edrophonium, but by neither neostigmine nor physostigmine. The ordering of potency was neostigmine > physostigmine > > edrophonium. CONCLUSION: These data indicate that the nicotinic receptor may be involved, at least in part, in the antinociceptive action of cholinesterase inhibitor at the spinal level, and M1 receptor subtype may be a common pharmacologic site of action. Moreover, neostigmine is more potent than physostigmine and edrophonium.

Idiopathic normal pressure hydrocephalus predominantly with prolonged fever and hyponatremia.

Described is a patient with hydrocephalus and a gait disorder with associated prolonged fever and hyponatremia. The authors made a diagnosis of normal pressure hydrocephalus (NPH) and performed a ventriculoperitoneal shunt, which improved the gait disturbance, accompanied by resolution of the fever and hyponatremia.

Selective photothermal interaction using an 805-nm diode laser and indocyanine green in gel phantom and chicken breast tissue.

Laser immunotherapy, a novel therapy for breast cancer, utilises selective photothermal interaction to raise the temperature of tumour tissue above the cell damage threshold. Photothermal interaction is achieved with intratumoral injection of a laser-absorbing dye followed by non-invasive laser irradiation. When tumour heating is used in combination with immunoadjuvant to stimulate an immune response, antitumour immunity can be achieved. In this study, the selective photothermal effect was investigated using gel phantom and chicken breast tissue. An 805-nm diode laser and indocyanine green (ICG) were used. An ICG-containing gelatin phantom was constructed to simulate targeted tumour tissue. The target gel was buried inside chicken breast tissue and the tissue-gel construct was irradiated by the laser. Temperatures at different locations in the construct were measured during the laser irradiation. For comparison, the thermal effect of an Nd:YAG laser on the tissue-gel construct was also investigated. Selective heating of target gel containing 0.27% ICG and buried 1 cm below the chicken tissue surface was achieved with the 805-nm diode laser using a power of 0.85 W and beam radius of 1 cm. The target gel experienced a temperature increase of more then 6 degrees C whereas the surrounding chicken breast tissue experienced only a minor temperature increase. The feasibility of this experimental set-up has been shown. It will be used in the future to optimise treatment parameters such as laser power, laser beam radius, and dye concentration.

Effects of intracoronary calcium chloride on regional oxygen balance and mechanical function in normal and stunned myocardium in dogs.

BACKGROUND: Brief myocardial ischaemia has been demonstrated to result in mechanical and coronary endothelial dysfunction, in which calcium may play a role. We examined whether the mechanical and vascular responses to calcium are altered in postischaemic, reperfused myocardium. METHODS: Regional myocardial oxygen consumption (MVO2), mechanical function and coronary blood flow (CBF) in response to calcium chloride (0.10, 0.25, 0.50 and 0.75 mg ml(-1) of CBF) directly infused into the left anterior descending (LAD) artery were determined before (normal) and 30 min after a 15-min-period of LAD occlusion (stunned) in an open-chest canine model. Percentage segment shortening (%SS) and percentage postsystolic shortening (%PSS) in the LAD territory were determined using ultrasonic crystals and CBF using a Doppler transducer. Myocardial extraction of oxygen (EO2) and lactate (Elac) was calculated. RESULTS: The infusion of calcium chloride resulted in dose-dependent increases in %SS and MVO2 but did not affect %PSS in normal myocardium. These changes were accompanied by parallel increases in CBF, resulting in no change in EO2. In stunned myocardium, the responses to calcium chloride were not significantly altered, with the exception of a reduction in %PSS. However, ischaemia and reperfusion itself significantly reduced %SS and Elac and increased %PSS. CONCLUSIONS: These data suggest that calcium chloride improves regional systolic and diastolic function both in normal and stunned myocardium. Calcium chloride is unlikely to cause direct coronary vasoconstriction or to deteriorate regional mechanical function in postischaemic myocardium.

A novel class of highly potent, selective, and non-peptidic inhibitor of Ras farnesyltransferase (FTase).

Design, synthesis and structure-activity relationship of a class of aryl pyrroles as farnesyltransferase inhibitors are described. In vitro and in vivo evaluation of a panel of these inhibitors led to identification of 2 (LB42908) as a highly potent (IC(50)=0.9 nM against H-Ras and 2.4 nM against K-Ras) antitumor agent that is currently undergoing preclinical studies.