Linking: a dynamic electrophysiologic phenomenon in macroreentry circuits

The term "linking" has been used specifically to describe the mechanism for perpetuation of functional anterograde bundle branch block: namely, repetitive transseptal retrograde concealed penetration by impulses propagating along the contralateral bundle. We present selected examples that demonstrate tht linking-type phenomena actually have a wide spectrum of expression in human macroreentry circuits, particularly those incorporating either the bundle branches and His bundle or the normal pathway and Kent bundle. The examples presented are as follows: (1) persistent retrograde functional conduction delays in the His-Purkinje system during right ventricular pacing, (2) anterograde Kent bundle condution at rapid rates, dependent on prior block in the normal pathway, (3) persistent anterograde functional infra-His block of atrial impulses during rapid ventricular pacing in the presence of a retrogradely conducting accessory pathway, and (4) transient advancement of His activation with ventricular fusion complexes during overdrive ventricular pacing of bundle branch reentrant tachycardia. Based on these examples, we characterize linking as a generalized electrophysiologic phenomenon in which each successive impulse entering a macroreentry circuit propagates preferentially along one limb because of functional block in the contralateral limb resulting from the effects of the prior impulse. It is proposed that such functional block may be dynamically maintained either by repetitive impulse interference, which perpetuates local refractoriness (examples No. 1 to 3), or by repetitive impulse collision (example No. 4). The general conceptual scheme outlined can be applied to specific electrophysiologic phenomena associated with a wide variety of reentry circuits in man.     

Pakistan’s Response to COVID-19: Overcoming National and International Hypes to Fight the Pandemic

The COVID-19 outbreak started as pneumonia in December 2019 in Wuhan, China. The subsequent pandemic was declared as the sixth public health emergency of international concern on January 30, 2020, by the World Health Organization. Pakistan could be a potential hotspot for COVID-19 owing to its high population of 204.65 million and its struggling health care and economic systems. Pakistan was able to tackle the challenge with relatively mild repercussions. The present analysis has been conducted to highlight the situation of the disease in Pakistan in 2020 and the measures taken by various stakeholders coupled with support from the community to abate the risk of catastrophic spread of the virus.     

An Overview of the Treatment Options Used for the Management of COVID-19 in Pakistan: Retrospective Observational Study

BackgroundSince the first reports of COVID-19 infection, the foremost requirement has been to identify a treatment regimen that not only fights the causative agent but also controls the associated complications of the infection. Due to the time-consuming process of drug discovery, physicians have used readily available drugs and therapies for treatment of infections to minimize the death toll.ObjectiveThe aim of this study is to provide a snapshot analysis of the major drugs used in a cohort of 1562 Pakistani patients during the period from May to July 2020, when the first wave of COVID-19 peaked in Pakistan.MethodsA retrospective observational study was performed to provide an overview of the major drugs used in a cohort of 1562 patients with COVID-19 admitted to the four major tertiary-care hospitals in the Rawalpindi-Islamabad region of Pakistan during the peak of the first wave of COVID-19 in the country (May-July 2020).ResultsAntibiotics were the most common choice out of all the therapies employed, and they were used as first line of treatment for COVID-19. Azithromycin was the most prescribed drug for treatment. No monthly trend was observed in the choice of antibiotics, and these drugs appeared to be a random but favored choice throughout the months of the study. It was also noted that even antibiotics used for multidrug resistant infections were prescribed irrespective of the severity or progression of the infection. The results of the analysis are alarming, as this approach may lead to antibiotic resistance and complications in immunocompromised patients with COVID-19. A total of 1562 patients (1064 male, 68.1%, and 498 female, 31.9%) with a mean age of 47.35 years (SD 17.03) were included in the study. The highest frequency of patient hospitalizations occurred in June (846/1562, 54.2%).ConclusionsGuidelines for a targeted treatment regime are needed to control related complications and to limit the misuse of antibiotics in the management of COVID-19.     

Self-care experiences of Pakistani patients with COPD and the role of family in self-care: A phenomenological inquiry

Self-care enables patients in improving quality of life and reducing hospital admissions. Research explored the experiences of patients about breathlessness, sleep problems and complication management in chronic obstructive pulmonary disease (COPD). However, the self-care experiences and the role of the family in self-care are underexplored. This study aimed to understand the self-care experiences of patients with COPD and explore the role of the family in self-care. An interpretive phenomenological inquiry was used, and 13 patients were interviewed in 2019 from two hospitals in Pakistan. The inclusion criteria were patients above 30 years of age at any stage of COPD, who received a confirmed diagnosis of COPD and were receiving the treatment, and engaged in self-care at their homes or communities. The interviews lasted for 35–60 min. Ricoeur's interpretation theory was used for data analysis comprising steps explanation, naive understanding and in-depth understanding. Self-care emerged as a complex individual and familial endeavour affected by personal, social and economic factors. Poverty was one of the core determinants of self-care. Patients emphasised the spiritual, cultural and traditional approaches to self-care. Future research is warranted to develop better understanding of spiritual and cultural self-care and how these dimensions of self-care affect patients’ self-care behaviours.     

Acute hyperthermia following stereotactic radiosurgery for pituitary adenoma

A 71-year-old male presented with a large pituitary adenoma with superior extension into the optic chiasm and suprasellar cistern. He was treated with stereotactic radiosurgery to a dose of 16 Gy. Approximately 1 h after radiosurgery he developed fever; his temperature peaked at 105.1 degrees F and normalized about 20 h later. This case demonstrates that acute hyperthermia is a potential complication following high dose stereotactic radiosurgery for large pituitary tumours.     

Volume fast spin-echo imaging of the cervical spine

RATIONALE AND OBJECTIVES: The authors prospectively evaluated a T2-weighted, three-dimensional (3D) volume, fast spin-echo (SE) pulse sequence in assessment of the cervical spine and compared it with standard imaging protocol. MATERIALS AND METHODS: Eighteen patients with neck pain underwent magnetic resonance (MR) imaging at 1.5 T with two-dimensional (2D) fast SE and axial 3D gradient-echo (GRE) protocols and with an additional sagittal T2-weighted volume fast SE protocol. The spinal cord and canal, neural foramina, and intervertebral disks were assessed by two neuroradiologists, and the results were compared with reports from the standard protocol. The quality of the partition (direct sagittal) and reconstructed images were evaluated. RESULTS: No differences existed in the assessment of spinal cord disease or disk herniation with 2D fast SE and volume fast SE imaging. Some mild variation occurred in assessment of the neural foramina. Partition images demonstrated a high level of resolution and contrast, while reconstructed images had consistently lower quality. However, this did not impede detection and grading of disk or spinal abnormalities, which were adequately shown on volume fast SE sagittal images. Neural foramina were well demonstrated on axial reconstructions from volume fast SE imaging. CONCLUSION: Volume fast SE imaging provides information about the spinal cord, canal, disks, and neural foramina that is comparable to the information provided by routine imaging. Its thinner sections and multiplanar reconstruction capability are advantages over 2D imaging. Its greater tissue contrast with better visualization of the cervical cord, greater signal-to-noise ratio, and less susceptibility artifact are advantages over 3D GRE imaging.     

Interactions of Phosphodiester and Phosphorothioate Oligonucleotides with Intestinal Epithelial Caco-2 Cells

Purpose. Oral bioavailability for antisense oligonucleotides has recently been reported but the mechanistic details are not known. The proposed oral delivery of nucleic acids will, therefore, require an understanding of the membrane binding interactions, cell uptake and transport of oligonucleotides across the human gastro-intestinal epithelium. In this initial study, we report on the cell-surface interactions of oligonucleotides with human intestinal cells. Methods. We have used the Caco-2 cell line as an in vitro model of the human intestinal epithelium to investigate the membrane binding interactions of 20-mer phosphodiester (PO) and phosphorothioate (PS) oligonucleotides. Results. The cellular association of both an internally [³H]-labelled and a 5end [³²P]-labelled PS oligonucleotide (3.0% at 0.4 µM extracellular concentration) was similar and was an order of magnitude greater than that of the 5end [³²P]-labelled PO oligonucleotide (0.2%) after 15 minutes incubation in these intestinal cells. The cellular association of PS was highly saturable with association being reduced to 0.9% at 5 µM whereas that of PO was less susceptible to competition (0.2% at 5 µM, 0.1% at 200 µM). Differential temperature-dependence was demonstrated; PS interactions were temperature-independent whereas the cellular association of PO decreased by 75% from 37°C to 17°C. Cell association of oligonucleotides was length and pH-dependent. A decrease in pH from 7.2 to 5.0 resulted in a 2- to 3-fold increase in cell-association for both backbone types. This enhanced association was not due to changes in lipophilicity as the octanol:aqueous buffer distribution coefficients remained constant over this pH range. The ability of NaCl washes to remove surface-bound PS oligonucleotides in a concentration-dependent manner suggests their binding may involve ionic interactions at the cell surface. Cell-surface washing with the proteolytic enzyme, Pronase^®, removed approximately 50% of the cell-associated oligonucleotide for both backbone types. Conclusions. Binding to surface proteins seems a major pathway for binding and internalization for both oligonucleotide chemistries and appear consistent with receptor (binding protein)-mediated endocytosis. Whether this binding protein-mediated entry of oligonucleotides can result in efficient transepithelial transport, however, requires further study.     

A Field Test of the Sweat Patch

The sweat patch is a new, noninvasive method designed to estimate the ethanol consumption of drinking subjects. It consists of salt-impregnated absorbent pads protected by a plastic chamber with attached water-tight adhesive. The patch reportedly collects transepidermal fluid at a steady rate for up to 10 days. Recent laboratory research has indicated a linear relationship between the concentration of ethanol in transepidermal fluid and mean concentration of ethanol in blood. Levels of ethanol in the sweat patch allowed identification of persons drinking at least 0.5 g of ethanol/kg/day with 100% sensitivity and specificity. The study reported here was conducted to test the field effectiveness of this sweat patch in normal, active research subjects. First, several pretests were conducted to determine the optimal location of the patch on the body and its fluid uptake at various sites. A laboratory experiment using nonalcoholic subjects was conducted to replicate previous work, and methods of measuring ethanol concentration in the patch were refined. A field test of the patch was then carried out. Healthy active volunteers drank a single "moderate" dose of ethanol (0.5 g of ETOH/kg of body weight) and then remained abstinent for the next 3 days. A week later, a "heavy" dose (1.0/kg of body weight) was consumed. Only a trace of ethanol was detected in any of the patches worn in either experiment. The patch did not measure ethanol in the transepidermal fluid under field conditions. Thus, further design modifications and pilot testing are required before the full benefits of this unobtrusive measure of drinking can be realized.