Unveiling Breakthroughs in Post-resuscitation Supportive Care for Out-of-Hospital Cardiac Arrest Survivors: A Narrative Review.

Survivors of out-of-hospital cardiac arrest (OHCA) experience significant mortality rates and neurological impairment, potentially attributed to the hypoxic-ischemic injury sustained amid the cardiac arrest episode. Post-resuscitation care plays a crucial role in determining outcomes for survivors of OHCA. Supportive therapies have proven to be influential in shaping these outcomes. However, targeting higher blood pressure or oxygen levels during the post-resuscitative phase has not been shown to offer any mortality or neurological benefits. In terms of maintaining hemodynamic instability after resuscitation, it is recommended to use norepinephrine rather than epinephrine. While extracorporeal cardiopulmonary resuscitation has shown promising results, targeted temperature management has been found ineffective in improving outcomes despite its previous potential. This review also investigates various challenges and barriers associated with the practical implementation of these supportive therapies in clinical settings. The review also highlights areas ripe for future research and proposes potential directions to further enhance post-resuscitation supportive care for OHCA survivors.

Beta-Blockers and Their Current Role in Maternal and Neonatal Health: A Narrative Review of the Literature.

Beta-blockers are a class of medications that act on beta-adrenergic receptors and are categorized as cardio-selective and non-selective. They are principally used to treat cardiovascular conditions such as hypertension and arrhythmias. Beta-blockers have also been used to treat non-cardiogenic indications in non-pregnant individuals and the pediatric population. In pregnancy, labetalol is the mainstay treatment for hypertension and other cardiovascular indications. However, contraindications to certain sub-types of beta-blockers include bradycardia, heart failure, obstructive lung diseases, and hemodynamic instability. There is conflicting evidence of the adverse effects on fetal and neonatal health due to a scarce safety and efficacy profile, and further studies are necessary to understand the pharmacokinetics of the different classes of beta-blockers in pregnancy and fetal health. Understanding the hemodynamic changes during the stages of pregnancy is important to target a more beneficial therapy for both mother and fetus as well as better neonatal outcomes. Beta-blocker use in the pediatric population is less documented in studies but does have the potential to treat various cardiogenic and non-cardiogenic conditions. Future comprehensive studies would further benefit the direction of beta-blocker treatment during pregnancy in neonates and pediatrics.

Discovery of novel predisposing coding and noncoding variants in familial Hodgkin lymphoma.

Familial aggregation of Hodgkin lymphoma (HL) has been demonstrated in large population studies, pointing to genetic predisposition to this hematological malignancy. To understand the genetic variants associated with the development of HL, we performed whole genome sequencing on 234 individuals with and without HL from 36 pedigrees that had 2 or more first-degree relatives with HL. Our pedigree selection criteria also required at least 1 affected individual aged <21 years, with the median age at diagnosis of 21.98 years (3-55 years). Family-based segregation analysis was performed for the identification of coding and noncoding variants using linkage and filtering approaches. Using our tiered variant prioritization algorithm, we identified 44 HL-risk variants in 28 pedigrees, of which 33 are coding and 11 are noncoding. The top 4 recurrent risk variants are a coding variant in KDR (rs56302315), a 5' untranslated region variant in KLHDC8B (rs387906223), a noncoding variant in an intron of PAX5 (rs147081110), and another noncoding variant in an intron of GATA3 (rs3824666). A newly identified splice variant in KDR (c.3849-2A>C) was observed for 1 pedigree, and high-confidence stop-gain variants affecting IRF7 (p.W238∗) and EEF2KMT (p.K116∗) were also observed. Multiple truncating variants in POLR1E were found in 3 independent pedigrees as well. Whereas KDR and KLHDC8B have previously been reported, PAX5, GATA3, IRF7, EEF2KMT, and POLR1E represent novel observations. Although there may be environmental factors influencing lymphomagenesis, we observed segregation of candidate germline variants likely to predispose HL in most of the pedigrees studied.

A Generic Sequential Stimulation Adapter for Reducing Muscle Fatigue during Functional Electrical Stimulation.

BACKGROUND: Clinical applications of conventional functional electrical stimulation (FES) administered via a single electrode are limited by rapid onset neuromuscular fatigue. "Sequential" (SEQ) stimulation, involving the rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings. METHODS: The SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4 and 200 Hz, 10 and100 mA, and 50 and 2000 µs, respectively. RESULTS: A total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, failing at a frequency of 200 Hz. CONCLUSION: The SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.

Dynamic actin remodeling in response to lysophosphatidic acid.

Lysophosphatidic acid (LPA) is a multifunctional regulator of actin cytoskeleton that exerts a dramatic impact on the actin cytoskeleton to build a platform for diverse cellular processes including growth cone guidance, neurite retraction and cell motility. It has been implicated in the formation and dissociation of complexes between actin and actin binding proteins, supporting its role in actin remodeling. Several studies point towards its ability to facilitate formation of special cellular structures including focal adhesions and actin stress fibres by phosphoregulation of several actin associated proteins and their multiple regulatory kinases and phosphatases. In addition, multiple levels of crosstalk among the signaling cascades activated by LPA, affect actin cytoskeleton-mediated cell migration and chemotaxis which in turn play a crucial role in cancer metastasis. In the current review, we have attempted to highlight the role of LPA as an actin modulator which functions by controlling activities of specific cellular proteins that underlie mechanisms employed in cytoskeletal and pathophysiological events within the cell. Further studies on the actin affecting/remodeling activity of LPA in different cell types will no doubt throw up many surprises essential to gain a full understanding of its contribution in physiological processes as well as in diseases.Communicated by Ramaswamy H. Sarma.

Comparison of Urdu Versions of the Resilience Scale and the Resilience Scale for Adults.

BACKGROUND AND PURPOSE: Several methodological challenges are associated with measuring resilience in women. This study compares the 14-item Resilience Scale (RS-14) and the Resilience Scale for Adults (RSA) in a community sample of women. METHODS: Data were collected from 120 women residing in low socioeconomic areas of Karachi, Pakistan. Construct validity, internal consistency, and responsiveness were calculated. RESULTS: Both scales demonstrated satisfactory psychometric characteristics. The total RS-14 score was significantly associated with all subscales of the RSA. However, two items of the RS-14 did not show any association with any of the subscales of the RSA. Medium effect size was noted on the "structured style"subscale of the RSA. CONCLUSION: Differences between the scales concluded that the Urdu version the of RSA yielded improved results in this sample.

Social support intervention to promote resilience and quality of life in women living in Karachi, Pakistan: a randomized controlled trial.

OBJECTIVES: This study tested the efficacy of a 6-week social support intervention for enhancing resilience and quality of life among women living in low socioeconomic areas of Karachi, Pakistan. METHODS: One hundred and twenty women were randomly allocated to the intervention (n = 60) or control group (n = 60). Women in the intervention group attended a 6-week social support program, while those in the control group attended a single mental health awareness session. Outcome variables were measured via the resilience scale-14 item (RS-14), the resilience scale for adults (RSA), and World Health Organization quality of life brief scale (WHOQOL-BREF). RESULTS: Compared to participants in the control group, women in the intervention group reported improvements in resilience measured by RS-14 (p = 0.022) and the structured style subscale of the RSA (p = 0.043). A medium effect size was also measured on the structured style subscale (d = 0.6, 95% CI = 0.62874, 2.57126). No significant findings were noted on QOL scores. CONCLUSIONS: Community-based social support interventions are a gender-sensitive-, culturally appropriate-, and resource-sparing approach to promote women's resilience and improve their mental health.

ABC of multifaceted dystrophin glycoprotein complex (DGC).

Dystrophin protein in association with several other cellular proteins and glycoproteins leads to the formation of a large multifaceted protein complex at the cell membrane referred to as dystrophin glycoprotein complex (DGC), that serves distinct functions in cell signaling and maintaining the membrane stability as well as integrity. In accordance with this, several findings suggest exquisite role of DGC in signaling pathways associated with cell development and/or maintenance of homeostasis. In the present review, we summarize the established facts about the various components of this complex with emphasis on recent insights into specific contribution of the DGC in cell signaling at the membrane. We have also discussed the recent advances made in exploring the molecular associations of DGC components within the cells and the functional implications of these interactions. Our review would help to comprehend the composition, role, and functioning of DGC and may lead to a deeper understanding of its role in several human diseases.

Genetic etiology of oral cancer.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. It accounts for 2.5% of all new cancer cases and 1.9% of all cancer deaths annually. More than 90% of oral cancers (occurring in the mouth, lip, and tongue) are oral squamous cell carcinoma. The incidence rate of oral cancer varies widely throughout the world, with an evident prevalence in South Asian countries. This high incidence occurs in correlation with oral cancer-associated behaviors such as alcohol, tobacco use. Researchers have reported that these behaviors lead to genetic variations in tumor suppressor genes (APC, p53), proto-oncogenes (Myc), oncogene (Ras) and genes controlling normal cellular processes (EIF3E, GSTM1). Processes such as segregation of chromosomes, genomic copy number, loss of heterozygosity, telomere stabilities, regulations of cell-cycle checkpoints, DNA damage repairs and defects in notch signaling pathways are involved in causing oral cancer. In order to develop preventive and therapeutic options, it is necessary to comprehend the basic molecular mechanisms forcing oral tumorigenesis. This review examines, in detail, the mechanisms of genetic alteration which are considered to be responsible for the initiation of oral cancer.

The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects.

AIMS: To study the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nilvadipine. METHODS: Five healthy adult volunteers received nilvadipine (4 mg) orally before and after a 6 day treatment with rifampicin. Blood and urine were collected and assayed for plasma nilvadipine and urinary 6beta-hydroxycortisol and cortisol. RESULTS: The treatment with rifampicin reduced the mean (+/- s.d.) AUC of nilvadipine from 17.4 +/- 8.4 to 0.6 +/- 0.4 microg l-1 h (mean difference -16.8 microg l-1 h, 95% CI -9.4, 24.2 microg l-1 h). While the administration of nilvadipine alone elicited a significant (P < 0.05) hypotensive (mean difference for diastolic blood pressure -8 mmHg, 95% CI -4, -12 mmHg) and reflex tachycardia (mean difference 5 beats min-1, 95% CI 1, 9 beats min-1), the treatment with rifampicin abolished these responses. The urinary 6beta-hydroxycortisol/cortisol ratio showed a significant (P < 0.05) increase from 10.3 +/- 4.0 to 50.3 +/- 24.6 by rifampicin: mean difference 40.1, 95% CI 20.4, 59.8. CONCLUSIONS: Because rifampicin may greatly decrease the oral bioavailability of nilvadipine, caution is needed when these two drugs are to be coadministered.

Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients.

Abnormalities in plasma composition of essential fatty acids (EFAs) may be associated with the etiology of pruritus and other skin problems in patients undergoing hemodialysis. To study whether an oral supplementation with omega-6 (n-6) EFAs would restore deranged plasma EFAs and ameliorate skin symptoms, 9 and 7 dialysis patients were randomly assigned to receive either gamma-linolenic acid (GLA)-rich evening primrose oil (EPO) or linoleic acid (LA) (2 g/day each) for 6 weeks. Plasma concentrations of EFA were analyzed by gas chromatography and uremic skin symptoms were assessed for dryness, pruritus and erythema by questionnaire and visual inspection in a double-blind manner. The patients given EPO exhibited a significant (p < 0.05) increase in plasma dihomo-gamma-linolenic acid (a precursor of anti-inflammatory prostaglandin E1) with no concomitant change in plasma arachidonic acid (a precursor of pro-inflammatory prostaglandin E2 and leukotriene B4). In contrast, those given LA exhibited a significant (p < 0.05) increase in LA but not in any other n-6 EFAs, whereas they exhibited a significant (p < 0.05) decrease in plasma docosahexaenoic acid. The patients given EPO showed a significant (p < 0.05) improvement in the skin scores for the three different uremic skin symptoms over the baseline values and a trend toward a greater improvement (0.05 < p < 0.1) in pruritus scores than those given LA. Results indicate that GLA-rich EPO would be a more favorable supplemental source than LA in terms of shifting eicosanoid metabolism toward a less inflammation status through modifying plasma concentrations of their precursor n-6 EFAs. Further studies are required to confirm the efficacy and safety of EPO therapy for the treatment of uremic pruritus.

Dihydropyridine type calcium channel blocker-induced turbid dialysate in patients undergoing peritoneal dialysis.

We previously reported that manidipine, a new dihydropyridine type calcium channel blocker, produced chylous peritoneal dialysate being visually indistinguishable from infective peritonitis in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) [Yoshimoto et al. 1993]. To study whether such an adverse drug reaction would also be elicited by other commonly prescribed calcium channel blockers in CAPD patients, we have conducted postal inquiry to 15 collaborating hospitals and an institutional survey in International Medical Center of Japan as to the possible occurrence of calcium channel blocker-associated non-infective, turbid peritoneal dialysate in CAPD patients. Our diagnostic criteria for drug-induced turbidity of dialysate as a) it developed within 48 h after the administration of a newly introduced calcium channel blocker to the therapeutic regimen, b) absence of clinical symptoms of peritoneal inflammation (i.e., pyrexia, abdominal pain, nausea or vomiting), c) the fluid containing normal leukocyte counts and being negative for bacterial and fungal culture of the fluid, and d) it disappeared shortly after the withdrawal of the assumed causative agent. Results showed that 19 out of 251 CAPD patients given one of the calcium channel blockers developed non-infective turbid peritoneal dialysis that fulfilled all the above criteria. Four calcium channel blockers were suspected to be associated with the events: benidipine [2 out of 2 (100%) patients given the drug], manidipine [15 out of 36 (42%) patients], nisoldipine [1 out of 11 (9%) patients] and nifedipine [1 out of 159 (0.6%)] in descending order of frequency. None of the patients who received nicardipine, nilvadipine, nitrendipine, barnidipine and diltiazem (25, 7, 2, 1 and 8 patients, respectively) exhibited turbid dialysate. In conclusion, we consider that certain dihydropyridine type calcium channel blockers would cause turbid peritoneal dialysate being similar to that observed in patients developing infective peritonitis. To avoid unnecessary antibiotic therapy the possibility of this adverse reaction should be ruled out whenever a CAPD patient receiving a dihydropyridine type calcium channel blocker develops turbid dialysate.

[Influence of rifampicin on antihypertensive effects of dihydropiridine calcium-channel blockers in four elderly patients].

Rifamicin, an antituberculosis agent, is one of the most potent inducers of hepatic drug-oxidation enzymes. Rifampicin can reduce the efficacy of several therapeutically important drugs (including verapamil and diltiazem) by accelerating systemic elimination or by increasing hepatic first-pass metabolism. Because dihydropyridine calcium-channel blockers are mainly metabolized by the liver, rifampicin may also increase the extraction of these drugs and thereby reduce their antihypertensive effects. Here we report four possible cases of interaction between rifampicin and dihydropiridine calcium-channel blockers. Rifampicin was given to treat tuberculosis in four elderly hypertensive patients whose blood pressure was well-controlled by one or more dihydropiridine calcium-channel blockers (nisoldipine, nifedipine, or barnidipine and manidipine), shortly after the start of antituberculosis therapy, their blood pressures rose. Either much greater doses of dihydropyridines or additional antihypertensive agents had to be given to keep blood pressure under control. After withdrawal of rifampicin, blood pressure fell in all patients and the doses of the antihypertensive agents had to be reduced. These findings indicate that rifampicin may lessen the antihypertensive effects of dihydropiridine calcium-channel blockers.

[Two cases of autosomal dominant polycystic kidney disease treated with hemodialysis associated with polycystic liver complications related to the cause of death].

As long-term survival has become possible in patients with autosomal dominant polycystic kidney disease (ADPKD) with progress in hemodialysis (HD), complications by various extrarenal diseases has presented new problems. Recent experience of two rare cases of ADPKD ending fatally due to complications by polycystic liver is presented. Case 1: A 60-year-old female with a family history of ADPKD without a past history of liver disease, was diagnosed as ADPKD at the age of 45 years. Hemodialysis was started at the age of 58 years. From 6 months prior to her death, abdominal circumference increased (body height: 149 cm, abdominal circumference: 100 cm). Dyspnea, abdominal pain and anorexia appeared and she died of hepatic failure leading to cachexia. Case 2: A 76-year-old female with a family history of ADPKD without a past history of liver disease, was started on HD at the age of 73 years. Abdominal circumference was 84 cm (body height: 138 cm). She was repeatedly admitted to and discharged from the hospital due to febrile episodes. Infection of polycystic liver was complicated by DIC and she died of gastrointestinal hemorrhage. Autopsy revealed abscess in some of the cysts in the liver. Hepatic cysts most frequently complicating ADPKD so far have presented with scarcely any clinical problems. Recently, however, cases of infection of hepatic cysts, portal hypertension and hepatic insufficiency have been reported. The relationship between these hepatic diseases and the prognosis of ADPKD has received attention. Increase in the number of cases of complications similar to the present cases is anticipated.

Famotidine-associated central nervous system reactions and plasma and cerebrospinal drug concentrations in neurosurgical patients with renal failure.

Central nervous system toxicity of H2-receptor antagonists has rarely been confirmed by the respective elevated cerebrospinal fluid drug concentrations. We observed two hemodialyzed neurosurgical patients in whom mental deterioration and convulsions developed after intravenous famotidine therapy (10 and 40 mg/day). Their cerebrospinal fluid drug concentrations were grossly elevated (i.e., 160 and 249 ng/ml) compared with those obtained from three other hemodialyzed neurosurgical patients who exhibited no central nervous system reactions (i.e., 47 to 85 ng/ml). In addition, the mean cerebrospinal fluid/plasma drug concentration ratio obtained from these five neurosurgical patients with renal failure (i.e., 0.46) and that from 10 other neurosurgical patients with normal renal function (i.e., 0.41) were about four times greater than that previously reported from non-neurosurgical patients with normal renal function (i.e., 0.12). Our observation suggests that patients with not only renal dysfunction but also following neurosurgical operations have an excessive accumulation of famotidine in the central nervous system and are more susceptible to the drug-induced adverse central nervous system reactions.

[Two case reports of refractory heart failure treated by continuous ambulatory peritoneal dialysis].

In this report, we present 2 cases of severe congestive heart failure and mild renal insufficiency in patients who underwent continuous ambulatory peritoneal dialysis (CAPD) after stabilization using the extracorporeal ultrafiltration method (ECUM). Long-term good control of congestive heart failure was achieved following the institution of CAPD. Case 1, a 58-year-old woman with rheumatic arthritis and diabetes mellitus had anteroseptal myocardial infarction at the age of 52. And case 2, a 68-year-old man, who underwent coronary artery bypass surgery at the age of 66 and had extensive anterior infarction after the operation. They were admitted to the hospital with dyspnea due to congestive heart failure. In both cases, systolic cardiac function was severely impaired and mild renal insufficiency was present at the time of hospitalization. After admission, symptomatic relief was not obtained by conventional therapies and symptoms of congestive heart failure worsened until the patients suffered from severe respiratory distress even at rest. ECUM was then instituted to remove excess fluid and clinical improvement was achieved. After the initiation of ECUM, responsiveness to diuretics was not restored, and the procedure was necessary every day or every other day for the prevention of symptoms due to fluid overload. About 20 days after the initiation of ECUM, CAPD was begun for the long-term control of congestive heart failure and renal failure, and for the purpose of hospital discharge. Good control of heart failure was achieved after the initiation of CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)

[Nephrotic syndrome with microcellular projections into the thickened basement membrane].

A 47 year-old patient with an 8-year history of proteinuria was admitted to our hospital in 1989. His laboratory data were compatible with nephrotic syndrome: total serum protein 5.9g/dl (albumin 3.0g/dl), total serum cholesterol 280mg/dl and total urinary protein excretion 5.0g/day. Renal biopsy specimens contained 27 glomeruli associated with sclerosis and collapse of loops under light microscopical examination. In addition, mesangial proliferation and thickening of the basement membrane were visualized. With immunofluorescent study granular IgG deposits were detected in the peripheral region of the glomeruli. Staining for IgA, IgM, C3, Clq, light chain and Congo-red were all negative. On electron microscopy, microtubules apparently resembling cellular projections appeared to thicken the basement membrane. We are tempted to conclude that the current case is an atypical glomerulopathy accompanied by a glomerular microtubular-like structure.

A drug-induced turbid peritoneal dialysate in five patients treated with continuous ambulatory peritoneal dialysis.

Turbid peritoneal dialysate is one of the heralding signs for infective peritonitis in patients treated with continuous ambulatory peritoneal dialysis (CAPD). Peritoneal dialysate drained from 5 out of 8 patients undergoing CAPD became turbid within 24 h after the administration of a new dihydropyridine type of calcium channel blocker, manidipine hydrochloride (10 or 20 mg/day). Although the dialysate was visually indistinguishable from that observed during infective peritonitis, no clinical manifestations being suggestive of infective peritonitis were observed. The turbid dialysate contained normal leukocyte counts (< 10 mm-3), and the bacterial (aerobic and anaerobic) and fungal cultures of the dialysate failed to produce organisms. Cytology of the dialysate showed no malignant cells. Biochemical analysis of the dialysate revealed that the fluid contained an elevated triglyceride concentration [range: 12 to 32 mg/100 ml (0.14 to 0.37 mmol/l], while the clear dialysate obtained from 9 uncomplicated CAPD-patients contained less than the detection limit of the assay for triglyceride [< 5 mg/100 ml (0.06 mmol/l)]. All patients were found to consume a nutritionally balanced diet consisting of 1800 to 2400 Kcal/day during the manidipine therapy. No appreciable change was observed in the mean (+/- SD) fasting serum triglyceride concentrations determined before and 24 h after the withdrawal of the manidipine therapy (194 +/- 84 and 186 +/- 106 mg/100 ml, respectively) in the 5 CAPD-patients with turbid peritoneal dialysate. Within 24 h after the withdrawal of the manidipine therapy the peritoneal dialysate became clear spontaneously and the triglyceride concentration in the dialysate was normalized in all of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Hemofiltrability of histamine H2-receptor antagonist, nizatidine, and its metabolites in patients with renal failure.

To study if an H2-receptor antagonist, nizatidine, and its metabolites [N-2-monodesmethylnizatidine (N-2-MDMN) and nizatidine sulfoxide (nizatidine S-Ox)] would be removed by an arteriovenous hemofiltration, the authors measured their plasma concentrations and amounts recovered in ultrafiltrate during 11 sessions of an intermittent hemofiltration performed in seven patients with renal failure who were given an oral administration of nizatidine (150 mg). The concentrations of the parent drug and its metabolites in plasma and ultrafiltrate were determined with a high-performance liquid chromatography with ultraviolet absorbance detection. The mean (+/- standard deviation [SD]) amounts of nizatidine removed by the procedure performed at the mean ultrafiltration rate of 18 (range, 11-25) mL/min over the mean duration of 179 (60 to 300) minutes accounted for 1.9 +/- 1.4% of the dose administered. The corresponding values for N-2-MDMN and nizatidine S-Ox were 0.3 +/- 0.2% and 0.2 +/- 0.2% of the molar dose of nizatidine, respectively. There was a significant correlation between the filtration rate and the hemofiltration clearance of nizatidine (r = .94, P < .001) or its active metabolite, N-2-MDMN (r = 0.83, P < .01), indicating that the sieving coefficient (Sc), an index of filtration efficiency, for these compounds is largely constant (0.59 and 0.67 for nizatidine and N-2-MDMN, respectively) under the current hemofiltration conditions.(ABSTRACT TRUNCATED AT 250 WORDS)