Heart Rate Variability Predicts Severe Hypotension after Spinal Anesthesia

Background: Hypotension due to vasodilatation after spinal anesthesia (SA) may be harmful. Heart rate variability, an indirect measure of autonomic control, may predict hypotension.

Methods: One hundred patients were studied. Retrospectively, heart rate variability was analyzed in 30 patients, classified depending on the lowest systolic blood pressure (SBP) after SA. Seventy patients were studied prospectively, assigned to one of two groups by their low to high frequency ratio (LF/HF) before SA. Sensitivity and specificity of LF/HF for prediction of decrease of SBP greater 20% of baseline were tested.

Results: Retrospective analysis showed differences of LF/HF depending on the degree of hypotension after SA. Prospective analysis demonstrated significant differences of SBP after SA depending on baseline LF/HF (mean +/- SD): low LF/HF (1.3 +/- 0.7) = > SBP: 91 +/- 8% of baseline versus high LF/HF (5.5 +/- 2.4) = > SBP: 66 +/- 10% of baseline (P < 0.05). Baseline LF/HF as well as high frequency and proportional decrease of SBP after SA correlated significantly, in contrast to baseline hemodynamic parameters heart rate and SBP. A receiver operator curve characteristic analysis showed a sensitivity and specificity of LF/HF > 2.5 of 85% to predict SBP decrease of greater than 20% of baseline after SA.     

Effects of lidocaine with and without epinephrine on plasma epinephrine and lidocaine concentrations and hemodynamic values during third molar surgery.

Lidocaine with epinephrine is currently the most common local anesthetic agent used for impacted third molar surgery. The purpose of the present study was to define the adverse hemodynamic effects and plasma concentrations of lidocaine and epinephrine on 17 healthy patients during the impacted teeth operations. Arterial blood pressure (systolic blood pressure, diastolic blood pressure), heart rate, peripheral oxygen saturation range, and electrocardiography were measured by an automatic noninvasive pressure device and monitor. High-performance liquid chromatography was used to measure the changes of plasma concentrations of epinephrine and lidocaine from blood samples taken 5 different times during the operation. We concluded that lidocaine-epinephrine is effective local anesthetic and had no important adverse events in healthy patients during the third molar surgery.     

Extra-chromosomal telomeric DNA in cells from Atm(-/-) mice and patients with ataxia-telangiectasia

Ataxia-telangiectasia (AT) is an autosomally recessive human genetic disease with pleiotropic defects such as neurological degeneration, immunodeficiency, chromosomal instability, cancer susceptibility and premature aging. Cells derived from AT patients and ataxia-telangiectasia mutated (ATM)-deficient mice show slow growth in culture and premature senescence. ATM, which belongs to the PI3 kinase family along with DNA-PK, plays a major role in signaling the p53 response to DNA strand breaks. Telomere maintenance is perturbed in yeast strains lacking genes homologous to ATM and cells from patients with AT have short telomeres. We examined the length of individual telomeres in cells from ATM(-/-) mice by fluorescence in situ hybridization. Telomeres were extensively shortened in multiple tissues of ATM(-/-) mice. More than the expected number of telomere signals was observed in interphase nuclei of ATM(-/-) mouse fibroblasts. Signals corresponding to 5-25 kb of telomeric DNA that were not associated with chromosomes were also noticed in ATM(-/-) metaphase spreads. Extrachromosomal telomeric DNA was also detected in fibroblasts from AT patients and may represent fragmented telomeres or by-products of defective replication of telomeric DNA. These results suggest a role of ATM in telomere maintenance and replication, which may contribute to the poor growth of ATM(-/-) cells and increased tumor incidence in both AT patients and ATM(-/-) mice.     

Improved high-performance liquid chromatography assay of doxorubicin: Detection of circulating aglycones in human plasma and comparison with thin-layer chromatography

Summary We compared doxorubicin and metabolite pharmacokinetic data obtained from thin-layer chromatography (TLC) and high-performance liquid chromatography (HPLC) assay of plasma samples from six patients who had been treated with doxorubicin. Duplicate 1-ml samples were extracted with chloroform: isopropanol (1:1) and assayed using a sensitive HPLC system incorporating a dual pump gradient with tetrahydrofuran as the mobile phase and fluorescence detection. Duplicate 1-ml samples from the same specimens were assayed using a modification of a previously described TLC assay. Areas under the curve for doxorubicin by HPLC (3.36±2.30 M · h) and TLC (4.16±2.50 M · h) were not significantly different (P=0.5). Terminal half-life of doxorubicin by HPLC (28.0±6.98 h) and TLC (23.2±7.8) (P=0.29) and the calculated total-body clearances by HPLC (0.55±0.29 l/min) and TLC (0.45±0.23) (P=0.55) were not significantly different. Areas under the curve for doxorubicinol by HPLC (2.75±1.4 M · h) and TLC (2.53±7.1 M · h) (P=0.73) showed no significant differences. HPLC detected a mixed 7-deoxydoxorubicinol aglycone-doxorubicin aglycone peak, 7-deoxydoxorubicin aglycone, and two nonpolar, unidentified metabolites. TLC detected the following aglycone metabolites: doxorubicin aglycone, doxorubicinol aglycone, 7-deoxydoxorubicinol aglycone, an unidentified polar metabolite, and several unidentified nonpolar metabolites. From these data we conclude that HPLC and TLC detect concentrations of doxorubicin and doxorubicinol from human plasma equally well to concentrations of 7.0 nM (4 pmol injected doxorubicin). Aglycones do circulate in human plasma at concentrations above the detection limits of both assays. Doxorubicinol aglycone, which is detected by TLC but not by HPLC, may be formed from artifactual breakdown of doxorubicinol during TLC development. Unidentified nonpolar compounds seen on HPLC and TLC may represent further doxorubicin metabolism than previously described.     

In vitro pharmacodynamic evaluation of VP-16-213 and implications for chemotherapy

Summary VP-16-213 (Etoposide) is an active antineoplastic agent which has undergone extensive evaluation of clinical dose escalation. To corroborate a putative dose-response relationship, we studied, in a modified clonogenic assay, various doses and durations of exposure. VP-16-213 at doses of 0.01, 0.05, 0.10, 0.50, 1.0, 5.0 and 10.0 g/ml, each with exposure durations of 1, 3, 18, and 30 h, was studied in vitro against two human tumor cell lines, MOLT and 9812. The doses and durations of exposure were chosen to approximate some of the pharmacokinetic values achievable in either standard-dose or high-dose clinical studies. The results, summarized as linear regression lines, demonstrate with statistical significance (p<0.03) that there is correlation between dose and cytotoxicity and between dose x duration of exposure (representing the area under the concentration-time curve) and cytotoxicity. Our in vitro data thus support the concept of intensive use of VP-16-213 to maximize antitumor activity. However, how best to accomplish the manipulation of dose and duration of exposure is not yet clear and will be the subject of future clinical investigations.Supported in part by Grant ROI CA39686 from the NIH (KR Hande)     

The evaluation of acute kidney injury due to ischemia by urinary neutrophil gelatinase-induced lipocalin (uNGAL) measurement in patients who underwent partial nephrectomy

International Urology and Nephrology - To investigate the role of urinary neutrophil gelatinase-induced lipocalin (uNGAL) measurement in the early diagnosis of acute kidney injury that may occur...     

The effect of renal artery-only or renal artery–vein clamping during partial nephrectomy on short and long-term functional results: Is clamping technique important?

Purpose

To evaluate the effect of artery-only (AO) and artery–vein (AV) clamping during partial nephrectomy (PN) on short- and long-term renal function outcome.

Methods

Medical records of 154 patients in the AO group and 192 patients in the AV group who underwent open and minimally invasive (laparoscopic/robotic) PN between January 2011 and January 2018 were retrospectively assessed. Preoperative patient and tumor-specific characteristics in addition to perioperative factors and renal function outcomes were compared. The change in the estimated glomerular filtration rate (eGFR) from postoperative 1–3 days, 12 and 24 months after surgery was calculated. Acute kidney injury (AKI) was defined a as a?>?25% reduction in eGFR.

Results

There were no statistically significant differences between the clamping techniques in terms of postoperative 1–3 days, 12 and 24 months eGFR change percentage and risk of progression to chronic kidney disease (CKD). No significant difference in short- and long-term renal functions was found between the minimally invasive or open AO and AV clamping subgroups at any time point. In multivariate analysis, the R.E.N.A.L score (AO group p?=?0.026, AV group p?<?0.001) and preoperative eGFR (AO group p?<?0.001, AV group p?=?0.010) were strong predictors of the acute kidney injury in both groups. Older age (AO group p?=?0.045, AV group p?=?0.010) and preoperative eGFR (AO group p?=?0.008, AV group p?=?0.002) were significantly associated with CKD progression at 2-year follow-up in both groups.

Conclusion

AV clamping does not adversely affect postoperative renal function compared to AO clamping. Preoperative patient- and tumor-related factors are more important for renal function regardless of the clamping technique.

     

The “vaccine” hubbub: Viral load comparisons of SARS-CoV-2 Delta and Omicron variants against different vaccine–booster vaccine combinations

There is a significant body of evidence showing that efficient vaccination schemes against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is helping control the coronavirus disease 2019 (COVID-19) pandemic. However, this goal cannot be achieved without real world data highlighting the impact of vaccines against viral spread. In this study, we have aimed at differentially investigating the impact of COVID-19 vaccines (CoronaVac, Pfizer/BioNTech, Astra/Zeneca Oxford, Janssen) used in North Cyprus in limiting the viral load of Delta and Omicron variants of SARS-COV-2. We have utilized real-time quantitative polymerase chain reaction cycle threshold values (Ct values) as a proxy of viral load of the two SARS-CoV-2 variants. Our results indicate that the administration of at least two doses of the messenger RNA-based Pfizer/BioNTech vaccine leads to the lowest viral load (highest Ct values) obtained for both Omicron and Delta variants. Interestingly, regardless of the vaccine type used, our study revealed that Delta variant produced significantly higher viral loads (lower Ct values) compared with the Omicron variant, where the latter was more commonly associated with younger patients. Viral spread is a crucial factor that can help determine the future of the pandemic. Thus, prioritizing vaccines that will play a role in not only preventing severe disease but also in limiting viral load and spread may contribute to infection control strategies.     

Tension-type headache in children: A clinical evaluation

BACKGROUND: Headache Society (IHS) criteria for episodic tension-type headache were included in the present study. Pain characteristics, associated symptoms, and stress-triggering factors were evaluated. Psychiatric and psychosocial evaluations were performed according to DSM-IV criteria. RESULTS: Pain was bilateral in 93.7% of patients and bitemporal in 50% of children. The intensity of pain increased with motion and stress in more than half of the patients, while pain decreased with rest and massage in 43.7% of patients. Ten of the 16 (62.5%) patients were diagnosed as having a psychiatric disorder. The most common stress-triggering factors were difficulty in adaptation at school and relationship problems with family members. All of the children reported 26 stress factors. Of these stress factors, 20 (76.9%) were reported by children diagnosed with psychiatric disorder. CONCLUSION: These results suggest that in children with tension-type headache a thorough psychiatric evaluation should be performed to rule out underlying psychiatric disorders.