Effect of glycated albumin on phenytoin binding in elderly patients with type II diabetes mellitus

We evaluated the effect of glycated albumin on phenytoin protein binding in 36 elderly (age range 63-94 yrs) patients with type II diabetes mellitus (DM) under diet management. Serum was spiked with 15 mg/L phenytoin and incubated. A serum ultrafiltrate was obtained from each sample for determining total and free phenytoin concentrations. Glycated hemoglobin was determined by boronate-affinity chromatography, and glycated albumin was separated from nonglycated fractions with boronate-agarose gel. Glycated hemoglobin in the study group ranged from 4.3-14.6% (mean 7.8 +/- SD 2.1%) and glycated albumin ranged from 3.7-12.5% (7.4 +/- SD 2.6%). We observed no correlation between glycated albumin and the percentage of free phenytoin (r2 = -0.14; p = 0.419). The concentration of nonglycated albumin ranged from 0.66-4.28 g/dl (mean 3.45 +/- 0.67 g/dl) and was calculated from measured total and glycated albumin concentrations. A correlation between the free fraction of phenytoin and nonglycated albumin was not demonstrated (r2 = 0.22, p = 0.22). In addition, a correlation was not observed between total glycated albumin and the free fraction of phenytoin (r2 = -0.095; p = 0.58). We conclude that elderly patients with type II DM under diet control do not have significant alterations in phenytoin protein binding. The use of total serum phenytoin levels therefore appears appropriate for determining phenytoin dosages in elderly patients with well controlled type II DM.     

Levodopa improves physical fatigue in Parkinson's disease: a double-blind, placebo-controlled, crossover study.

We quantitatively investigated the effect of carbidopa/levodopa (25/100) on physical fatigue during finger tapping and force generation in a double-blind, placebo-controlled crossover study. Parkinson's disease (PD) subjects were randomly assigned to carbidopa/levodopa or placebo for Visit 1 or 2 and participated in the following two studies: (1) Finger tapping. Twenty-five PD patients used their index fingers to strike two keys 20 cm apart on a musical instrument digital interface (MIDI) keyboard. The slopes of the regression line of dwell time and movement time were used to assess the rate of fatigue development. (2) Force generation. Twelve PD patients contracted the wrist extensors maximally to obtain a baseline maximum voluntary contraction (BMVC) force. Then they repetitively contracted the wrist extensors at 50% of the BMVC for 7 seconds and rested for 3 seconds. An interval maximum voluntary contraction (IMVC) was measured every three repetitions. Fatigue was defined as an IMVC of less than 60% of the BMVC. The slope of the regression line of IMVC was used to assess the rate of force decline. These two studies were repeated 1 hour after carbidopa/levodopa (25/100) or placebo. Subjects filled out the Multidimensional Fatigue Inventory (MFI) at the beginning of the first visit. Results showed that the slope of dwell time decreased with levodopa but not with placebo (P = 0.004). The rate of force decline also decreased with levodopa but not with placebo (P = 0.01). The subscores in the dimension of physical fatigue in the MFI did not correlate with the rate changes in dwell time or the rate changes in force decline. We concluded that (1) levodopa improves physical fatigue in finger tapping and force generation, (2) physical fatigue in Parkinson's disease is at least partially related to dopamine deficiency, and (3) the MFI measures different aspects of physical fatigue compared with those measured by finger tapping and force generation.     

The effect of subhypnotic doses of propofol on the incidence of pruritus after intrathecal morphine for Caesarean section

The effect of subhypnotic doses of propofol on intrathecal morphine-induced pruritus was studied in a prospective, randomly allocated, double-blind controlled trial. Fifty-eight women undergoing elective lower segment Caesarean section for a singleton fetus received spinal anaesthesia with 2.5 ml hyperbaric 0.5% bupivacaine and 0.2 mg of preservative-free morphine. They then received propofol 1 ml (10 mg) or Intralipid 1 ml (control group) intravenously after delivery. Pruritus was assessed using a five-point verbal rating scale at hourly intervals for 8 h. A second dose of their allocated treatment drug was administered at the first recording of significant pruritus. The pruritus score was reassessed after 5 min and the treatment was repeated if pruritus remained. There were no differences between the groups in the onset of pruritus or its successful treatment. No adverse side-effects were associated with this dose of propofol. There were no differences in the incidence of post-operative nausea and vomiting between the two groups. Subhypnotic propofol is not an effective treatment for intrathecal morphine-induced pruritus in women following Caesarean section.     

Postbiopsy renal transplant arteriovenous fistulas: color Doppler US characteristics

Color Doppler ultrasound (US) with point-spectral analysis was performed on eight patients with postbiopsy renal transplant arteriovenous fistulas. Waveform analysis of the supplying artery documented decreased resistive indices in all cases and increased flow velocities in seven. The peak-systolic flow velocity in the arteries supplying the fistulas ranged from 55 to 180 cm/sec (mean, 92 cm/sec), while the range in normal arteries was 20-52 cm/sec (mean, 32 cm/sec). The resistive indices of the arteries supplying the fistulas ranged from 0.31 to 0.50 (mean, 0.45), while the resistive indices of the normal arteries ranged from 0.60 to 0.92 (mean, 0.74). Arterialization of the venous waveform from the draining vein was also documented in all cases. In six cases, the increased flow velocities resulted in increased color saturation toward white in the supplying artery (n = 2) or in both the artery and the draining vein (n = 4), which was detectable on the realtime image. In six cases, flow turbulence resulted in localized tissue vibration, which appeared as random color assignment in extravascular renal parenchyma adjacent to the fistula. Knowledge of these imaging and Doppler characteristics should aid in the identification of renal transplant arteriovenous fistulas with color Doppler US.     

Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient.     

Unusual proton exchange properties of Z-form poly[d(G-C)

Real-time solvent-exchange NMR has been used to study the proton exchange in Z-form poly[d(G-C)]. In 4.5 M NaCl the most slowly exchanging protons (about two orders of magnitude slower than in B-DNA) are identified as the guanine imino proton and the cytosine amino proton hydrogen bonded to the guanine carbonyl. Both protons exchange at the same rate and the exchange follows single-exponential kinetics and cannot be catalyzed, implying that the exchanges of the two protons both occur from the same transient solvent-exposed state. The exchange depends strongly on temperature and the activation energy for exchange (≈22 kcal/mol) is the same as the activation energy for the B → Z transition. The rate of proton exchange is identical with the B → Z transition rate, both measured in 4.5 M NaCl. The correlation between the B → Z kinetics and the proton exchange also extends to 3.25 M NaClO₄ solutions, in which both rates are 5 times faster. This unexpected parallelism between the B → Z transition kinetics and the Z exchange kinetics indicates that the rate-limiting steps in the two processes are similar.     

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.     

A randomised,controlled, double blind,non‐inferiority trial of ultrasound‐guided fascia iliaca block vs. spinal morphine for analgesia after primary hip arthroplasty

We performed a single centre, double blind, randomised, controlled, non‐inferiority study comparing ultrasound‐guided fascia iliaca block with spinal morphine for the primary outcome of 24‐h postoperative morphine consumption in patients undergoing primary total hip arthroplasty under spinal anaesthesia with levobupivacaine. One hundred and eight patients were randomly allocated to receive either ultrasound‐guided fascia iliaca block with 2 mg.kg^?1 levobupivacaine (fascia iliaca group) or spinal morphine 100 μg plus a sham ultrasound‐guided fascia iliaca block using saline (spinal morphine group). The pre‐defined non‐inferiority margin was a median difference between the groups of 10 mg in cumulative intravenous morphine use in the first 24 h postoperatively. Patients in the fascia iliaca group received 25 mg more intravenous morphine than patients in the spinal morphine group (95% CI 9.0–30.5 mg, p < 0.001). Ultrasound‐guided fascia iliaca block was significantly worse than spinal morphine in the provision of analgesia in the first 24 h after total hip arthroplasty. No increase in side‐effects was noted in the spinal morphine group but the study was not powered to investigate all secondary outcomes.