Leukocyte adhesion defect‐I: rare primary immune deficiency

Leukocyte adhesion defect I is a rare disorder (1:1,000,000) caused by diminished expression of CD‐18 β2 integrins on leukocytes leading to abnormal adhesion, migration, and chemotaxis. Clinical manifestations include delayed separation of umbilical cord, omphalitis, recurrent severe infections, impaired wound healing, persistent oral ulcers, and severe periodontitis in primary and permanent dentition. A 5‐year‐old girl, second‐born child to parents with consanguinity, presented with pain and mobility of lower teeth. There was history of recurrent infections and multiple hospital admissions with CD18 level‐3% and frame shift mutation in ITGB2, on 21q22.3. There were scars on hands and feet. Oral examination revealed multiple missing teeth and periodontitis in primary dentition. Oral prophylaxis and palliative treatments were performed with periodic follow‐ups. Interdisciplinary care is ubiquitous for patients with immune deficiencies. Early consultation with pediatric dentists and exploration of medical history is essential for diagnosis and treatment of rare diseases.     

Cerebral microbleeds: a guide to detection and clinical relevance in different disease settings

Cerebral microbleeds have emerged as an important new imaging marker of cerebral small vessel disease. With the development of MRI techniques that are exquisitely sensitive to paramagnetic blood products, such as T2*-weighted gradient-recalled echo and susceptibility-weighted sequences, microbleeds have been detected in ever-increasing numbers of patients in stroke and cognitive clinics, as well as in healthy older people and in a variety of other rarer diseases and syndromes. Detection of cerebral microbleeds has clinical implications with respect to the diagnosis of the underlying small vessel disease, the safety of antithrombotic use, and the risk of symptomatic intracerebral haemorrhage, cognitive impairment and dementia. This article provides a guide to the detection and clinical relevance of cerebral microbleeds in different conditions based on a comprehensive review of the literature and own findings in research and clinical practice.     

Cybersecurity for Cardiac Implantable Electronic Devices: What Should You Know?

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.     

Acute,sub-acute and general pharmacological evaluation of 5-(3,4-methylenedioxyphenyl)-4-ethyl-2E,4E-pentadienoic acid piperidide (SK-20): A novel drug bioavailability enhancer

An efflux pump inhibitor, SK-20 (5-(3,4-methylenedioxyphenyle)-4 ethyl-2E,4E-pentadienoic acid piperidide), was assessed for its toxicity at three different pharmacological profiles: acute, sub-acute and general pharmacology with pharmacokinetics. In acute study, the SK-20 was found safe up to a dose of 2000 mg/kg (b.wt.); and at sub-acute, dosages of 50 and 100 mg/kg (b.wt.) were found to be safe. However, dosages of 200 mg or above per kg (b.wt.) showed some morphological alterations in cellular architecture of both liver and kidneys in both sexes, viz., mild vascular congestion along with sporadic hemorrhages and infiltration into renal and hepatic parenchyma by mononucleate cell. General pharmacological studies did not result into any alterations in analgesic, convulsions, rectal temperatures and in the rhythm or the rate of the intestinal motility or the secretion of the bile. While the respiratory and the cardiac rate remained normal, the only parameter to show was the blood pressure, which at all the doses tested, showed a tendency toward reduction. Characteristically, the SK-20 at all doses influenced pentobarbital-induced hypnosis positively and negatively to spontaneous motor activity in a dose dependent manner. Pharmacokinetics of SK-20 revealed it to have retention time at 10.2 min and half life 2.47 h.     

The Influence of Xylazine and Clonidine on Lung Ultrasound–Induced Pulmonary Capillary Hemorrhage in Spontaneously Hypertensive Rats

Induction of pulmonary capillary hemorrhage (PCH) by lung ultrasound (LUS) depends not only on physical exposure parameters but also on physiologic conditions and drug treatment. We studied the influence of xylazine and clonidine on LUS-induced PCH in spontaneously hypertensive and normotensive rats using diagnostic B-mode ultrasound at 7.3 MHz. Using ketamine anesthesia, rats receiving saline, xylazine, or clonidine treatment were tested with different pulse peak rarefactional pressure amplitudes in 5 min exposures. Results with xylazine or clonidine in spontaneously hypertensive rats were not significantly different at the three exposure pulse peak rarefactional pressure amplitudes, and thresholds were lower (2.2 MPa) than with saline (2.6 MPa). Variations in LUS PCH were not correlated with mean systemic blood pressure. Similar to previous findings for dexmedetomidine, the clinical drug clonidine tended to increase susceptibility to LUS PCH.     

Angiopoietins as promising biomarkers and potential therapeutic targets in brain injury

Traumatic brain injury (TBI) and sub-arachnoid hemorrhage (SAH) are major causes of long-term disability, mortality, and enormous economic costs to society. The full spectrum of neurological damage created by TBI or SAH is not usually manifested at the time of injury, but evolves gradually over the course of hours to days (or weeks) following these injuries. Angiopoietins, important regulators of vascular structure and function, are hallmark indicators of vascular injury and may therefore represent promising targets in the treatment of SAH and TBI. In animal models and human tissues, normal intracerebral and pial vessels show strong expression of Angiopoietin-1 (Ang-1), but only minimal expression or presentation of Angiopoietin-2 (Ang-2). After several types of neurotrauma, the ratios of Ang-1 and Ang-2 expression in brain microvessel are disturbed and appear to contribute to the remarkable loss of blood–brain barrier (BBB) in these injuries. Angiopoietins levels, and perhaps more importantly, Angiopoietin ratios (1:2) may have novel and important diagnostic and prognostic uses in TBI and SAH brain injury. Ang-1/2 evaluation in plasma, serum and cerebrospinal fluid may provide new therapeutic modalities which can modify ‘secondary’ forms of brain injury after TBI and SAH.     

Melioidosis in India and Bangladesh: A review of case reports

Objective: To conduct an epidemiological and clinical review of published case reports of melioidosis from India and Bangladesh. Methods: Data from published case reports were abstracted and summarized. We further compared the clinical epidemiology of the melioidosis cases in India with case series from highly endemic areas in Northern Australia and Southeast Asia to elucidate any differences in presentations and risk factors between the regions.Results: We identified a total of 99 cases published between 1953 and June 2016, originating from India(n=85) or Bangladesh(n=14). Cases were predominantly male and ranged in age from 1 month to 90 years. Diabetes mellitus was the most common risk factor reported(58%). About 28% of the cases had history of exposure via high-risk occupations or exposure to contaminated water. The overall case fatality rate(CFR) was 26%. Factors influencing mortality included the occurrence of septic shock(CFR, 80%), environmental exposure(CFR,39%), primary presentation of pneumonia(CFR, 38%), misdiagnosed and/or mistreated cases(CFR, 33%) or the presence of a risk factor(CFR, 29%). Because of the small number of cases in Bangladesh, pattern of clinical epidemiology is limited to India. Soft tissue abscess(37%)was the most common clinical presentation reported from India followed by pneumonia(24%)and osteomyelitis/septic arthritis(18%). Neurological melioidosis(n=10, 12%) presented as pyemic lesions of the brain or meninges. A few cases of prostatic abscess(n=4) in men and parotid abscess(n=4) were also noted. The above patterns were consistent with case series from Southeast Asia and Northern Australia for the most part, in terms of risk factors associated with infection and factors influencing mortality. Differences included clinical presentation of pneumonia which was notably lower than that reported in Southeast Asia and Northern Australia; a higher proportion of neurological and parotid abscess presentation; and a lower CFR compared to that reported in case series in Southeast Asia. About 39% of the cases were misdiagnosed and/or mistreated, suggesting underreporting and under estimation of the true disease burden. Conclusions: The concentration of melioidosis cases in southern and eastern states in India and in Bangladesh, which share climatic conditions and rice farming activities with known endemic areas in Southeast Asia, suggests an endemicity of melioidosis in this region. Thus, increased awareness among healthcare personnel, particularly among clinicians and nurses practicing in rural areas, and improved surveillance through case registries is essential to guide early diagnosis and prompt treatment.