Takotsubo Cardiomyopathy in Traumatic Brain Injury

Background

Takotsubo cardiomyopathy (TC) is a well-known complication after aneurysmal subarachnoid hemorrhage and has been rarely described in patients with traumatic brain injury (TBI).

Methods

Case report and review of literature.

Results

Here, we report a 73-year-old woman with mild traumatic brain injury (TBI) presenting in cardiogenic shock. Takotsubo cardiomyopathy (TC) was diagnosed by repeated echocardiography. Cardiovascular support by inotropic agents led to hemodynamic stabilization after initiation of levosimendan. Cardiac function fully recovered within 21 days. We performed an in-depth literature review and identified 16 reported patients with TBI and TC. Clinical course and characteristics are discussed in the context of our patient.

Conclusion

Takotsubo cardiomyopathy is under-recognized after TBI and may negatively impact outcome if left untreated.

     

Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency

Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network.     

Antisense peptide nucleic acid targeting GluR3 delays disease onset and progression in the SOD1 G93A mouse model of familial ALS

Glutamate excitotoxicity is strongly implicated as a major contributing factor in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). Excitotoxicity results from elevated intracellular calcium ion (Ca(2+)) levels, which in turn recruit cell death signaling pathways. Recent evidence suggests that alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit (GluR) stoichiometry is a dominant factor leading to excess Ca(2+) loading in neurodegeneration. In particular, the Ca(2+) permeable glutamate receptor subunit 3 (GluR3) has been implicated in several neurologic conditions such as bipolar disorder and epilepsy. Recent proteomic analysis within our group on the copper zinc superoxide dismutase (SOD1)(G93A) transgenic mouse model of familial ALS (FALS) reveals a potentially deleterious upregulation of GluR3 in spinal cord compared to that in wild-type littermates. Based on this finding we designed a 12mer antisense peptide nucleic acid (PNA) directed against GluR3. This sequence significantly reduced levels of GluR3 protein and protected neuroblastoma x spinal cord (NSC-34) cells against death induced by the AMPA receptor-specific agonist (S)-5-fluorowillardiine. We subsequently treated SOD1(G93A) mice thrice weekly with intraperitoneal injections of the antisense PNA (2.5 mg/kg) commencing at postnatal day 50. Mice treated with the antisense sequence had significantly extended survival compared to mice injected with a nonsense sequence. Western blot analysis, however, did not reveal a significant reduction in GluR3 protein levels in whole extracts of the lumbar spinal cord. These results suggest that interference with the GluR3 component of the AMPA receptor assembly may be a novel strategy for controlling excitotoxic destruction of motor neurons and may lead to new therapeutic opportunities for the treatment of human ALS.     

Pyogenic granuloma complicating pulsed-dye laser therapy for cherry angioma

A 37 year-old-woman presented for cosmetic removal of a 7-mm (diameter) cherry angioma on her right anterior thigh. Various treatment options were discussed and removal of the lesion using pulsed-dye laser was carried out. The patient returned 5 weeks later complaining of bleeding from the treatment site, which on examination showed a 23 × 23-mm friable nodular lesion with the typical appearance of a pyogenic granuloma. This lesion was removed by shave excision, curettage and electrodessication. Histopathological examination confirmed the diagnosis of pyogenic granuloma. This is a rare occurrence post pulsed-dye laser therapy that physicians may choose to discuss with patients prior to performing this procedure.     

High and low body temperature during the initiation of ventilation for near-term lambs

AimsRecent literature suggests hypothermia may protect against lung injury. We evaluated body temperature as a variable in lung inflammation due to oxygenation and mechanical ventilation following delivery of near-term lambs.MethodsTwin fetuses were randomized prior to delivery at 140 d GA (term 150 d): unventilated controls, normothermic ventilated with room air, normothermic ventilated with 100% oxygen, low temperature ventilated (target 35 °C) with 100% oxygen, and high temperature (target 40 °C) with 100% oxygen. Lambs were intubated for gentle mechanical ventilation (tidal volume 7–8 ml/kg). Temperature targeting was with radiant warmers and plastic wrap for normothermia, with heat lamps for hyperthermia, and with ice packs for hypothermia. Lambs were euthanized after 2 h mechanical ventilation. Post-mortem, bronchoalveolar lavage fluid and lung tissue samples were evaluated for inflammatory responses by measuring inflammatory cell counts, protein, myeloperoxidase, protein carbonyl, and pro-inflammatory cytokine mRNA.ResultsTarget temperatures were achieved by 30 min of age and tightly maintained for the 2 h study. There were no differences in physiologic variables among groups except those directly resulting from study protocol—PaO₂ from air vs. 100% oxygen and body temperature. Indicators of inflammation increased similarly in all ventilated groups compared to unventilated controls.ConclusionModerate hyperthermia or hypothermia did not affect lung injury responses to the initiation of ventilation at birth in near-term lambs.     

Detection of the Philadelphia chromosome in acute lymphoblastic leukemia by pulsed-field gel electrophoresis

The Philadelphia (Ph1) chromosome is an acquired abnormality in the malignant cells of 10% to 25% of patients with acute lymphoblastic leukemia (ALL). Unlike chronic myelogenous leukemia (CML), where the molecular detection of the Ph1 chromosome is relatively straightforward using conventional Southern hybridization analysis, the detection of the Ph1 chromosome in ALL is complicated by the existence of several molecular subtypes, and the fact that translocation breakpoints are dispersed over a large genomic area. To circumvent these difficulties, we investigated pulsed-field gel electrophoresis (PFGE) to determine if this method could be used directly on clinical samples to detect the Ph1 chromosome in ALL. We report that, in a study of seven patients with Ph1-positive ALL, we could easily detect the Ph1 using only a single PFGE analysis, regardless of the Ph1 subtype, and we could confirm that the translocations occur either within or very near the BCR gene in all seven. We conclude that PFGE is a useful technique for the detection of the Ph1 in ALL, which ultimately may find wide applicability in the detection of other chromosomal abnormalities in other malignancies.     

Properties of the temperament and character inventory in a Chinese sample

OBJECTIVE: To determine the influence of language and culture on the temperament and character (TCI) measure in a Chinese sample. METHOD: We translated the TCI into Mandarin and had a non-psychiatric sample of Malaysian Chinese subjects complete the TCI at baseline and at a 1-month retest, with subsets completing English or Mandarin versions alternatively or on both occasions. Analyses examine the TCI factor structure and any impact of language and culture on TCI scoring. RESULTS: We identified age, gender, occupation and language effects on TCI scale scores. Test-retest reliability was high and not compromised by language. Scale internal consistency was also high. Factor analyses of separate sets of TCI scales corresponded strongly to the structure identified in the TCI development studies. CONCLUSION: The results indicate that TCI is likely to have applicability to Chinese subjects, and argue against properties being constrained by the English language or by western culture.     

Differential cytostatic effect of sodium salicylate in human colorectal cancers using an individualized histoculture system

PURPOSE: Tumor metastasis is the major cause of colorectal cancer (CRC) mortality. Nonsteroidal antiinflammatory drugs (NSAIDs) such as aspirin have been shown to have an antineoplastic effect in CRC cell lines. Different patients, however, exhibit different chemosensitivity. In this study, we assessed the chemotherapeutic potential of sodium salicylate, an aspirin metabolite, by measuring its cytostatic effect in an individualized three-dimensional histoculture system. METHODS: Histocultured cancer tissues were treated with sodium salicylate at concentrations from 1 to 10 m M for 24 or 48 h. Inhibition of DNA synthesis was measured in terms of inhibition of bromodeoxyuridine (BrdU) incorporation.RESULTS: The concentration response of individual cancer tissues could be categorized into four groups ranging from the most to the least sensitive to sodium salicylate. Of 20 cancer tissues, 12 (60%) showed a concentration-effect relationship with sodium salicylate in the clinically relevant concentration range (IC50 1.2+/-0.4 to 3.8+/-0.5 m M). Doubling the exposure time decreased the IC50 in four specimens, suggesting that a similar inhibition might be achieved with a lower concentration over an extended time. None of the right-sided cancers was sensitive to sodium salicylate ( P=0.002). CONCLUSIONS: Sodium salicylate had a cytostatic effect on the majority of histocultured CRC tissues. The varying chemosensitivity of the cancers possibly reflected underlying differences, for example in relation to cancer site, thus emphasizing further the usefulness of this clinically relevant system in tailoring chemotherapy to the individual patient.     

A survival-stratification model of human colorectal carcinomas with beta-catenin and p27kip1

BACKGROUND: The stabilization and nuclear translocation of beta-catenin are early events in the majority of sporadic colorectal carcinomas (CRC). beta-catenin up-regulates c-Myc and cyclin D1, which antagonize the association of the cyclin-dependent kinase (Cdk) inhibitor, p27(kip1), with Cdk2, thus allowing cell cycle progression through G1 to S-phase. Lack of p27 is a significant predictor of poor survival in a series of 136 CRC specimens. A combination of molecules in the same pathway may be a better prognostic factor. METHODS: The expression of beta-catenin, c-Myc, and cyclin D1 in relation to patients' survival and clinicopathologic parameters in the same series was evaluated by immunohistochemistry. RESULTS: Intense nuclear overexpression of beta-catenin, but not a lack of cell membrane or cytoplasmic expression, is a significant predictor of poor survival by both univariate (P = 0.0029) and multivariate analyses (P = 0.004, risk ratio =3.8), suggesting that beta-catenin is retained in the nucleus to function as an oncogene. None of the patients with high nuclear beta-catenin and low p27 expression survived 5 years or more whereas 65% of patients with all other combinations of the two markers survived (P < 0.0001). This combination is also a significant and independent prognostic factor (P = 0.001; risk ratio = 9.7). Overexpression of c-Myc is associated with higher mortality rates, but the expression of cyclin D1 has no prognostic significance. CONCLUSIONS: The combined expression of beta-catenin and p27 can stratify patients into markedly different survival groups, possibly via their antagonistic effects on metastasis promotion.