Cainpeele9372

We aimed to characterise the population pharmacokinetics of fentanyl in adults and to determine the minimum effective concentration (MEC) and minimum effective analgesic concentration (MEAC) of i.v. fentanyl in patients after major abdominal open surgery.

In the pharmacokinetic study, subjects received an intravenous bolus of fentanyl 100 μg during operation, and arterial blood was sampled at pre-set intervals. In addition, data from previously published fentanyl pharmacokinetic studies were incorporated to build a pharmacokinetic model. In the MEAC study, subjects were asked to rate their pain every 10 min using a VAS (0=no pain, 10=most severe pain) in the PACU. The first blood sample was obtained when wound pain was rated as ≥3 at rest or ≥5 during compression. Then, fentanyl 50 μg was administered every 10 min until the pain intensity had decreased to <3 at rest and <5 during compression, at which point the second blood was sampled and the first MEAC of fentanyl was measured. The same procedure was repeated to obtain a third sample (MEC) and a fourth sample (second MEAC).

In the population pharmacokinetic study (n=95), the plasma concentration of fentanyl over time was well-described by the three-compartment mammillary model using an allometric expression. The V1, V2, V3, Cl, Q1, and Q2 of a 70 kg subject were 10.1, 26.5, 206 L, 0.704, 2.38, and 1.49 L min

, respectively. OligomycinA In the MEAC study (n=30), the median (inter-quartile range) MEC and MEAC were 0.72 (0.58-1.05) ng ml

, and 0.99 (0.76-1.28) ng ml

, respectively.

These results provide a scientific basis for the use of fentanyl for acute postoperative pain management in surgical patients.

KCT0003273 (http//cris.nih.go.kr).

KCT0003273 (http//cris.nih.go.kr).

Malignant hyperthermia (MH) susceptibility is an inherited condition, diagnosed either by the presence of a pathogenic genetic variant or by invitro caffeine-halothane contracture testing. Through a multi-dimensional approach, we describe the implications of discordance between genetic and invitro test results in a patient with a family history of possible MH.

The patient, whose brother had a possible MH reaction, underwent the caffeine-halothane contracture test (CHCT) according to the North American MH Group protocol. Screening of the complete RYR1 and CACNA1S transcripts was done using Sanger sequencing. Additional functional analyses included skinned myofibre calcium-induced calcium release sensitivity, calcium signalling assays in cultured myotubes, and in silico evaluation of the effect of any genetic variants on their chemical environment.

The patient's CHCT result was negative but she carried an RYR1 variant c.1209C>G, p.Ile403Met, that is listed as pathogenic by the European Malignant Hypertould be re-evaluated.

Spasmodic dysphonia (SD) is a rare disease and its epidemiological status is unclear. This review aimed to explore the current prevalence and clinical features of SD in Japan.

We reviewed Japanese surveys of SD and compared them to surveys reported from other countries. We focused on SD prevalence, clinical features (SD type, sex and age), and treatment modalities.

The SD prevalence in Japan was 3.5-7.0/100,000, similar to that in Rochester (NY, USA) and Iceland. Adductor SD predominated (90-95%) and females were four-fold more likely to be affected than males. Mean age at onset was approximately 30 years in Japan. Several years elapsed from onset to diagnosis. The most frequent treatment was botulinum toxin injection, and surgical intervention, particularly type 2 thyroplasty is becoming more popular.

Our review demonstrated some differences of clinical features of SD in Japan compared with other countries, such as a greater female predominance and younger age of onset. Many physicians and patients may be unfamiliar with the clinical features of SD leading to delayed of diagnosis. Therefore, we proposed diagnostic criteria to facilitate early diagnosis and an appropriate choice of treatment modalities.

Our review demonstrated some differences of clinical features of SD in Japan compared with other countries, such as a greater female predominance and younger age of onset. Many physicians and patients may be unfamiliar with the clinical features of SD leading to delayed of diagnosis. Therefore, we proposed diagnostic criteria to facilitate early diagnosis and an appropriate choice of treatment modalities.

We offer collagenase Clostridium histolyticum (CCH) injections to all patients with a Dupuytren contracture and a palpable cord. We assessed whether more severe contractures respond less well or recur more frequently.

From a database of 502 CCH injections, 386 (77%) had a complete dataset with minimum 1-year face-to-face follow-up. Contracture severity was assessed using the Tubiana system grade 1 (27%), grade 2 (49%), grade 3 (19%), and grade 4 (5%). Patients received a single intralesional injection of 0.58 mg CCH followed by manipulation. Finger position was measured at 6 to 12 weeks, 6 months, and 1 year. Failure to break the cord, skin tears, and any adverse events were noted. Recurrence was defined as a failure to maintain any prior correction to within 20°.

There were 17 failures (4%) and 6 allergic reactions (1%). We found 31% corrected completely, with approximately half remaining corrected at 1 year. We achieved 43° (95% confidence interval, 40°-46°) correction of combined deformity, with 11° (95% confidence interval, 9°-13°) correction attrition over 1 year. Sixteen percent of treated digits experienced a recurrence with no difference between Tubiana grades, and one-third chose further treatment. Following treatment, Tubiana grade 1 contractures improved by 78% in comparison with higher grade contractures (55%-67% relative correction). By 1 year, all grades had a similar mean 46% relative correction. A complete correction was seen in 61% of grade 1 contractures, with more severe contractures less likely to correct completely (9%-24%). A 31% skin tear rate had no impact on outcome, recurrence, or long-term morbidity.

CCH may treat any Dupuytren cord regardless of severity. Although contracture may recur, few patients pursue further treatment within 1 year.

Therapeutic IV.

Therapeutic IV.