Evaluation of the pattern of treatment, level of anticoagulation control, and outcome of treatment with warfarin in patients with non-valvar atrial fibrillation: a record linkage study in a large British population

Objective: To evaluate how well patients with non-valvar atrial fibrillation (NVAF) were maintained within the recommended international normalised ratio (INR) target of 2.0–3.0 and to explore the relation between achieved INR control and clinical outcomes.

Design: Record linkage study of routine activity records and INR measurements.

Setting: Cardiff and the Vale of Glamorgan, South Wales, UK.

Participants: 2223 patients with NVAF, no history of heart valve replacement, and with at least five INR measurements.

Main outcome measures: Mortality, ischaemic stroke, all thromboembolic events, bleeding events, hospitalisation, and patterns of INR monitoring.

Results: Patients treated with warfarin were outside the INR target range 32.1% of the time, with 15.4% INR values > 3.0 and 16.7% INR values < 2.0. However, the quartile with worst control spent 71.6% of their time out of target range compared with only 16.3% out of range in the best controlled quartile. The median period between INR tests was 16 days. Time spent outside the target range decreased as the duration of INR monitoring increased, from 52% in the first three months of monitoring to 30% after two years. A multivariate logistic regression model showed that a 10% increase in time out of range was associated with an increased risk of mortality (odds ratio (OR) 1.29, p < 0.001) and of an ischaemic stroke (OR 1.10, p = 0.006) and other thromboembolic events (OR 1.12, p < 0.001). The rate of hospitalisation was higher when INR was outside the target range.

Conclusions: Suboptimal anticoagulation was associated with poor clinical outcomes, even in a well controlled population. However, good control was difficult to achieve and maintain. New measures are needed to improve maintenance anticoagulation in patients with NVAF.

     

Perinatal management of a preterm neonate affected by hyperprostaglandin E2 syndrome (HPS)

BACKGROUND: Neonates affected by hyperprostaglandin E(2) syndrome (HPS) present with severe polyuria. Both urinary losses as well as prostaglandin synthesis inhibitors may precipitate acute renal failure (ARF). AIM: Our goal was to maintain euvolaemia by replacement of urinary losses. PATIENT: Our patient was born prematurely with a family history typical of HPS. Urinary salt and water losses and PGE(2) excretion were determined in 2- to 4-h intervals. Salt and water were replaced accordingly. RESULTS: Within the first 48 h, urinary losses and PGE(2) increased continuously to 50 ml/kg/h and 374 ng/h/1.73 m(2), respectively. Following exposure to 0.05-0.5 mg/kg/d indomethacin, urinary output decreased steadily to 10-15/ml/kg/h.CONCLUSION: In euvolaemic preterm neonates with HPS and the need for excessive replacement of salt and water, inhibition of renal PGE(2) excretion with indomethacin effectively reduces polyuria and natriuresis without acutely compromising renal function.     

Testicular torsion and risk factors for orchiectomy

OBJECTIVE: To determine risk factors for testicular loss due to testicular torsion. DESIGN AND PARTICIPANTS: Medical records of patients aged 1 to 25 years with a principal diagnosis of testicular torsion were extracted from the 1998 Nationwide Inpatient Sample. Population-based rates of testicular torsion and orchiectomy were determined. Logistic regression was used to create a predictive model for orchiectomy. For comparison, medical records of patients aged 1 to 25 years with a principal diagnosis of testicular neoplasm were extracted. RESULTS: The sample comprised 436 participants. The estimated incidence of testicular torsion for males aged 1 to 25 years in the United States is 4.5 cases per 100,000 male subjects per year, and the estimated incidence of benign and malignant testicular tumors is 1.2 cases per 100,000. Of the estimated 2248 males diagnosed nationally in 1998 with testicular torsion, 762 (34%) had an orchiectomy. In the final multivariate model estimating the probability of orchiectomy, only age was significant. CONCLUSIONS: For males aged 1 to 25 years, testicular torsion is more common than testicular tumors, and increasing age is the sole identifiable risk factor for orchiectomy. We suggest that health care professionals educate prepubertal male patients about testicular torsion and the necessity of seeking timely care to reduce the risk of orchiectomy and of possible subsequent reduced fertility.     

Geologic constraints on the macroevolutionary history of marine animals

The causes of mass extinctions and the nature of taxonomic radiations are central questions in paleobiology. Several episodes of taxonomic turnover in the fossil record, particularly the major mass extinctions, are generally thought to transcend known biases in the geologic record and are widely interpreted as distinct macroevolutionary phenomena that require unique forcing mechanisms. Here, by using a previously undescribed compilation of the durations of sedimentary rock sequences, I compare the rates of expansion and truncation of preserved marine sedimentary basins to rates of origination and extinction among Phanerozoic marine animal genera. Many features of the highly variable record of taxonomic first and last occurrences in the marine animal fossil record, including the major mass extinctions, the frequency distribution of genus longevities, and short- and long-term patterns of genus diversity, can be predicted on the basis of the temporal continuity and quantity of preserved sedimentary rock. Although these results suggest that geologically mediated sampling biases have distorted macroevolutionary patterns in the fossil record, preservation biases alone cannot easily explain the extent to which the sedimentary record duplicates paleobiological patterns. Instead, these results suggest that the processes responsible for producing variability in the sedimentary rock record, such as plate tectonics and sea-level change, may have been dominant and consistent macroevolutionary forces throughout the Phanerozoic.     

Unilateral reduction of the cervical response in median SEP due to a vertebral fracture, unrecognized in plain films

We report on a patient presenting with hypaesthesia in first, second and third finger of the right hand following a motorcycle accident. Conventional X-ray showed only a mild dislocation in C6/C7 segment. Cervical MRI in order to prove a root avulsion, was reported to be normal. Somatosensory evoked potentials (SEP) revealed a reduced amplitude of the cervical response on right median nerve stimulation. Needle-EMG showed a mild reduced recruitment pattern in triceps brachii muscle compatible with an anterior root lesion. Reviewing MRI, a signal loss in the course of C7 root was suspicious for an articular process fracture. This was proved in a CT scan. This case report emphasizes the topodiagnostic value of the reduced amplitude of the cervical potential of median nerve SEP and the importance of the CT in evaluating cervical spine fractures, as plain films frequent fail to do so.     

The pattern of cognitive performance in CADASIL: a monogenic condition leading to subcortical ischemic vascular dementia

OBJECTIVE: Subcortical ischemic vascular lesions, which are closely related to small vessel disease, are a common substrate of cognitive impairment and dementia. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a monogenic variant of small vessel disease resulting from mutations in NOTCH3. Mutation carriers almost invariably develop cognitive deficits and eventually dementia. The current study describes the profile of cognitive abnormalities in CADASIL subjects. METHOD: A cross-sectional study of 65 mutation carriers (mean age=47.3 years, SD=10.5) and 30 matched comparison subjects (mean age=47.2 years, SD=14.0) was conducted. Participants underwent a series of assessments that included ratings of global cognition, the cognitive portion of the Vascular Dementia Assessment Scale, and specific tests of executive function and attention with measures of processing speed and error monitoring. RESULTS: CADASIL subjects had pronounced impairments of the timed measures (Stroop II and III, Trail Making Test, symbol digit, digit cancellation). Measures of error monitoring (Stroop III, Trail Making Test, symbol digit, maze task) were also significantly affected but to a lesser extent. Prominent deficits further included verbal fluency and ideational praxis. Recall, orientation, and receptive language skills were largely preserved. Subgroup analyses indicated a similar profile in subjects with early and advanced impairment of global cognitive performance. CONCLUSIONS: The findings highlight processing speed as the most substantial area of cognitive impairment in CADASIL subjects, with less pronounced yet significant deficits in other aspects of executive performance and attention. This profile of cognitive impairment is present at an early stage and enables the construction of targeted test batteries for clinical trials. It is hypothesized that the profile of dysfunction described here represents the core of the cognitive syndrome associated with small vessel disease and subcortical ischemic vascular lesions.     

Melatonin modulates intercellular communication among cultured chick astrocytes

Melatonin, a pineal neurohormone, mediates circadian and seasonal processes in birds and mammals. Diencephalic astrocytes are sites of action, at least in birds, since they express melatonin receptors and melatonin affects their metabolism. We tested whether astrocytic calcium waves are also modulated by melatonin. Calcium waves, which we found to be regulated in cultured chick glial cells by an IP(3)-dependent mechanism, were potentiated by physiological concentrations of melatonin. Melatonin also increased resting calcium levels and reduced gap junctional coupling among astrocytes, at concentrations that facilitated calcium waves. These modulatory effects were diminished by melatonin receptor blockade and pertussis toxin (PTX). Thus, melatonin induced a functional shift in the mode of intercellular communication, between junctional coupling and calcium waves, among glial cells. We suggest a mechanism where neuroglial physiology, involving GTP-binding protein signaling pathways, links rhythmic circadian outputs to pervasive neurobehavioral states.     

Stress exposure modulates peptidergic innervation and degranulates mast cells in murine skin

Stress is said to induce itchiness of the skin, exacerbate inflammatory skin diseases, and inhibit wound healing. Neuropeptides such as substance P (SP) may play a role in these processes. Recently, we were able to show that both stress or SP are associated with neurogenic inflammation and increased apoptosis in the murine hair follicle. Moreover, peptidergic cutaneous innervation is subject to lifelong plasticity due to its association with the cyclic growth of hair follicles. However, peripheral neuronal plasticity has never been reported in altered interactions between the nervous and immune systems under perceived stress. Here, we show for the first time plasticity of the cutaneous peptidergic innervation in response to stress. After exposure to sonic stress, the number of SP+ nerve fibers in the back skin of C57BL/6 mice with their hair follicles in the resting phase of the hair cycle (telogen-low numbers of nerve fibers) increased significantly. Such nerve fibers contacted mast cells more frequently. At the same time, the percentage of degranulated mast cells increased significantly associated with a rise in apoptotic cells in the skin. Increased numbers of peptidergic nerve fibers correlated with increased numbers of growth-associated protein 43 (Gap-43)+ nerve fibers, which is a marker for growing nerves. Thus, neuronal plasticity and increased neuro-immune interaction occur under stress and may alter inflammatory skin diseases and trophic functions in the skin where neurogenic inflammation plays a part.