Reaction to biological drugs: infliximab for the treatment of toxic epidermal necrolysis subsequently triggering erosive lichen planus

Toxic epidermal necrolysis (TEN) is a rare, life‐threatening skin reaction for which there is currently has no standardized treatment, despite its significant mortality. Biological agents such as tumour necrosis factor (TNF)‐α antagonists are emerging as a novel treatment for patients with TEN. We report a 32‐year‐old woman who developed TEN secondary to sulfasalazine, which was treated with infliximab. The infliximab treatment subsequently triggered erosive lichen planus (LP) involving the mouth and vulva. Clinicians should be aware that TNF‐α antagonists can cause LP as a paradoxical complication of treatment.     

Risk factors associated with having psoriatic arthritis in patients with cutaneous psoriasis

The aim of this study was to determine if the following characteristics were associated with the presence of psoriatic arthritis in a sample of psoriasis patients: race, family history of psoriasis and psoriatic arthritis, age of onset of psoriasis, smoking, alcohol consumption and the maximum body surface area (BSA) affected by psoriasis. This was a case–control study involving 400 psoriasis patients who attended the Psoriasis and Photo‐medicine clinic in the National Skin Center of Singapore over a 1‐year period. Cases were psoriasis patients with psoriatic arthritis while controls were psoriasis patients without psoriatic arthritis. The diagnosis of psoriatic arthritis was made by rheumatologists and participants completed a self‐administered standardized questionnaire. The maximum BSA involved was determined from the case notes. Psoriatic arthritis was not significantly associated with sex, race, age of onset of psoriasis, a family history of psoriasis, smoking and alcohol consumption but was significantly associated with a family history of psoriatic arthritis (P < 0.001) and the maximum body surface involved (P = 0.05). Using multivariate analysis to control for variables, the presence of psoriatic arthritis was significantly associated with a family history of psoriatic arthritis (odds ratio [OR] = 20.5; 95% confidence interval [CI] = 2.49–169.10) and the maximum BSA involved (OR = 2.52; 95% CI = 1.33–4.75). Indian psoriatic patients were more likely to have psoriatic arthritis compared to the other races. A family history of psoriatic arthritis and a greater maximum body surface involved may be associated with having psoriatic arthritis in this study population of psoriasis patients.     

ZRSR1 co-operates with ZRSR2 in regulating splicing of U12-type introns in murine hematopoietic cells

Recurrent loss-of-function mutations of spliceosome gene, ZRSR2, occur in myelodysplastic syndromes (MDS). Mutation/loss of ZRSR2 in human myeloid cells primarily causes impaired splicing of the U12-type introns. In order to further investigate the role of this splice factor in RNA splicing and hematopoietic development, we generated mice lacking ZRSR2. Unexpectedly, Zrsr2-deficient mice developed normal hematopoiesis with no abnormalities in myeloid differentiation evident in either young or ≥1-year old knockout mice. Repopulation ability of Zrsr2-deficient hematopoietic stem cells was also unaffected in both competitive and non-competitive reconstitution assays. Myeloid progenitors lacking ZRSR2 exhibited mis-splicing of U12-type introns, however, this phenotype was moderate compared to the ZRSR2-deficient human cells. Our investigations revealed that a closely related homolog, Zrsr1, expressed in the murine hematopoietic cells, but not in human cells contributes to splicing of U12-type introns. Depletion of Zrsr1 in Zrsr2 KO myeloid cells exacerbated retention of the U12-type introns, thus highlighting a collective role of ZRSR1 and ZRSR2 in murine U12-spliceosome. We also demonstrate that aberrant retention of U12-type introns of MAPK9 and MAPK14 leads to their reduced protein expression. Overall, our findings highlight that both ZRSR1 and ZRSR2 are functional components of the murine U12-spliceosome, and depletion of both proteins is required to accurately model ZRSR2-mutant MDS in mice.     

A novel technique of detecting MRI‐negative lesion in focal symptomatic epilepsy: Intraoperative ShearWave Elastography

Focal symptomatic epilepsy is the most common form of epilepsy that can often be cured with surgery. A small proportion of patients with focal symptomatic epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI). The most common pathology in this group is type II focal cortical dysplasia (FCD), which is a subtype of malformative brain lesion associated with medication‐resistant epilepsy. We present a patient with MRI‐negative focal symptomatic epilepsy who underwent invasive electrode recordings. At the time of surgery, a novel ultrasound‐based technique called ShearWave Elastography (SWE) was performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B‐mode ultrasound and 3‐T MRI. Electroencephalography (EEG), positron emission tomography (PET), and magnetoencephalography (MEG) scans demonstrated an abnormality in the right frontal region. On the basis of this finding, a depth electrode was implanted into the lesion. Surgical resection and histology confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here .     

Stroke impairment predictors of discharge function, length of stay, and discharge destination in stroke rehabilitation

OBJECTIVES: This article presents analytic results from a prospective study of 313 stroke rehabilitation patients, looking at the relative contributions of different stroke impairments toward prediction of discharge function, rehabilitation length of stay, and discharge destination after inpatient rehabilitation. The relationship between number of stroke risk factors and recurrence of strokes during rehabilitation was also evaluated. METHODS: A total of 313 subjects were enrolled consecutively. Information on type of stroke and individual stroke-related impairment was collected prospectively. Recurrent stroke, rehabilitation length of stay, discharge destination, discharge function, and available family support at discharge were documented. RESULTS: Rates of impairment occurrence and coexistence are presented. Analysis using linear (length of stay, discharge function) and logistic (discharge destination) regression revealed significant contributory predictive effects of admission balance, aphasia, number of impairments, and family support on length of stay; admission balance and number of impairments on discharge function; and admission balance, body neglect, and presence of family support on discharge destination. CONCLUSION: In addition to admission function and balance, other factors to consider in predicting length of stay for patients should include the number of stroke-related impairments and family support. For discharge destination prediction, the presence of body neglect should be considered in addition to balance and family support. Evaluation of patients for right-sided neglect and left-sided neglect is important.     

Chediak-Higashi gene in humans. I. Impairment of natural - killer function

Natural-killer (NK)-cell function was profoundly depressed in donors homozygous for the Chediak-Steinbrinck-Higashi syndrome (C-HS) gene when compared with age- and sex-matched normals. This apparent defect was not simply a result of a delayed response because little cytolysis was evident in kinetics experiments even after 24 h of incubation. NK cells from C-HS donors failed to lyse adherent (MDA, CEM, and Alab) or nonadherent (K562 and Molt-4) tumor cell lines or nontransformed human fetal fibroblasts. Therefore, the apparent C-HS defect was not a result of a shift in target selectivities. In addition, the depressed reactivity did not appear to be a result of suppressor cells or factors because: (a) enriched NK populations (nonadherent lymphocytes bearing receptors for the Fc portion of IgG) from C-HS donors were low in NK-cell function, (b) C-HS mononuclear cells did not inhibit the cytotoxicity of normal cells in coculture experiments, and (c) cells from the C-HS donors remained poorly reactive even after culture for up to 7 d. The nature of the defective NK activity in C-HS patients is not clear but may lie within the lytic mechanism rather than at the level of the recognition structure or population size because the frequency of target-binding cells was normal. In vitro NK activity could be partially restored by interferon treatment. Combined with the results presented in the following paper (4), these observations suggest that the C-HS gene causes a selective immunodeficiency disorder, mainly involving NK cells. This finding, in conjunction with the high incidence of spontaneous possibly malignant, lymphoproliferative disorders in these patients, may have important implications regarding the theory of immune surveillance mediated by NK cells.     

The use of amiodarone for in-hospital cardiac arrest at two tertiary care centres

BACKGROUND: Although amiodarone significantly increases survival to hospital admission when used in resuscitation of out-of-hospital pulseless ventricular tachycardia and fibrillation, there are limited data on its utility for in-hospital arrests. OBJECTIVES: To determine whether the use of amiodarone, as recommended by the year 2000 American Heart Association Advanced Cardiac Life Support guidelines, improved survival following its introduction to the resuscitation algorithm at two tertiary care institutions. METHODS: Charts of 374 cardiac resuscitations were retrospectively studied at the two institutions. Basic survival outcomes and demographic data were recorded for cardiac arrests with ventricular tachyarrhythmias qualifying for administration of antiarrhythmic agents. RESULTS: Qualifying rhythms were present in 95 patients. Clinical uptake of amiodarone was limited. In the 36 patients who received amiodarone, survival of resuscitation was 67% versus 83% (P=0.07) in the 59 patients receiving only other antiarrhythmic agents (chiefly lidocaine [94%]), while survival to discharge was 36.1% and 55.9% (P=0.06) in these two groups, respectively. CONCLUSIONS: Following two years' experience with the introduction of intravenous amiodarone for resuscitation in the institutions, use was less than 50% and no clinically observable survival benefit could be documented. Possible explanations for the difference between this experience and that found in out-of-hospital resuscitation trials include differing patient populations and operator bias during resuscitation. These results should provoke other institutions to question whether amiodarone has improved survival of cardiac arrest under the conditions prevailing in their hospitals. A patient registry or prospective, randomized trial will be required to assess what parameters affect the success of intravenous amiodarone for resuscitation in-hospital.     

Differentiating nonhigh-grade duct carcinoma in situ from benign breast lesions

This study was undertaken to determine the discriminating cytological features between nonhigh-grade duct carcinoma in situ (NHGDCIS) and benign breast lesions and to determine any histological characteristics which would influence the cytological categorization. Smears of 12 each of histologically confirmed NHGDCIS and benign breast lesions were reviewed with regard to cellularity, cell discohesion, nuclear atypia, crowding of cells, tubule formation, necrosis, and presence of bare atypical nuclei and regular bare bipolar nuclei, and statistically analyzed. Architectural pattern, presence of necrosis, and the size of the lesion assessed at histological examination were compared with the initial cytological categorization. NHGDCIS lesions showed more cell discohesion (P = 0.04), bare atypical nuclei (P = 0.05), necrosis (P = 0.03), and sparse bare bipolar nuclei (P = 0.02) than benign lesions. These differences were statistically significant. Cellularity (P = 0.8), nuclear atypia (P = 0.06), crowding of cells (P = 0.1), and tubule formation did not show a significant difference. Six (out of six lesions) with a solid architectural pattern and six (of seven) with necrosis could be cytologically categorized as suspicious or malignant. Size of the lesion did not influence this. We conclude that cell discohesion, bare atypical and bare bipolar nuclei, and necrosis are discriminating features between NHGDCIS and benign breast lesions and NHGDCIS lesions with a solid architectural pattern and necrosis are more likely to be satisfactorily categorized cytologically.     

Relative incidence of needle EMG abnormalities in the anterior tibial and gastrocnemius muscles

Foot drop resulting from weakness of the anterior tibial muscle is commonly encountered in clinical practice. We analyzed the incidence of needle electromyographic (EMG) abnormalities in the anterior tibial and gastrocnemius muscles from traumatic injuries to the sciatic nerve and also from different non-traumatic lower motor neuron conditions. In both traumatic and non-traumatic cases, the anterior tibial muscle showed relatively more EMG abnormalities compared to the gastrocnemius. It appears that the anterior tibial muscle is more susceptible to injury from a variety of pathologic conditions, as opposed to the gastrocnemius muscle.