A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita-associated keratoderma.

BACKGROUND: Severely debilitating plantar keratoderma pain is the most distressing clinical feature of pachyonychia congenita (PC). Several earlier publications have reported therapeutic success with plantar injections of botulinum toxin (Btx). OBJECTIVES: To describe our 4-year experience during which we administered a total of 30 plantar Btx injections to five patients with PC following an optimized protocol. METHODS: Five patients with PC (age 21-54 years) who were treated at our medical centre from April 2015 to June 2018 were included in the study. After an ultrasound-guided nerve block performed by an anaesthesiologist, the patients received plantar intradermal injections of Btx A. To ascertain the effect of the treatment, we used a dedicated quality-of-life questionnaire for patients with PC (PCQoL) and asked the patients to evaluate the intensity of eight parameters pertaining to their symptoms at baseline and before every treatment session. At study closure, patients were asked to evaluate the maximal improvement in the same eight parameters throughout the study period. RESULTS: All patients demonstrated a decrease in PCQoL scores during the follow-up period. All patients showed a significant improvement in PCQoL after the first treatment session and at the last evaluation (P = 0·043). The scores with the best improvement concerned morning feet burning and long-distance walking (> 500 m). The scores were significantly lower if the intervals between Btx injections were <100 days. CONCLUSIONS: Btx treatment of PC-associated keratoderma following an optimized protocol leads to a major change in patients' quality of life. What's already known about this topic? Plantar pain is considered by patients to be the most severe and debilitating manifestation of pachyonychia congenita (PC). Over the past few years, a number of reports have shown that plantar injections of botulinum toxin (Btx) reduce or even eliminate pain, blistering and callosities in patients with PC. However, the injection technique, doses of Btx and methods of anaesthesia varied between reports and patients. What does this study add? Here we report our 4-year experience in providing 30 treatments to five patients following an optimized protocol. Btx was found to provide a quantifiable improvement in all patients treated. What is the translational message? Btx treatment of PC-associated keratoderma using a structured approach, which includes the use of a sufficient dose of Btx (200-400 U of onabotulinumtoxinA or 500-1000 U of abobotulinumtoxinA), and regular intervals between treatment sessions (of < 100 days), leads to a major change in patients' quality of life.

Postcardiopulmonary bypass hypoxemia: a prospective study on incidence, risk factors, and clinical significance.

OBJECTIVE: To evaluate the clinical significance of low arterial oxygen tension-inspired oxygen concentration (PaO2-FIO2) ratio, as a measure of hypoxemia, in the early period after cardiac surgery with cardiopulmonary bypass (CPB); and to evaluate the preoperative, intraoperative, and postoperative factors contributing to the development of hypoxemia within the first 24 hours after cardiac surgery with CPB. DESIGN: Prospective observational study. SETTING: University hospital. PARTICIPANTS: Patients who underwent elective or emergency cardiac surgery with CPB (n = 466). INTERVENTIONS: Preoperative clinical and laboratory data were recorded, as were intraoperative and postoperative data regarding the PaO2-FIO2 ratio, fluid and drug therapy, and chest radiograph. Data analysis evaluated hypoxemia as depicted by the PaO2-FIO2 ratios at 1, 6, and 12 hours after surgery. Thereafter, the effect of the PaO2-FIO2 ratios on time to extubation, lung injury, and length of hospital stay was evaluated. The risk factors were analyzed in 3 separate periods: preoperative, intraoperative, and postoperative. Univariate and multivariate analyses were performed on each period separately. All data were analyzed in 2 consecutive steps: univariate analysis and multivariate analysis. MEASUREMENTS AND MAIN RESULTS: PaO2-FIO2 ratios after CPB were significantly lower compared with baseline values. Six patients (1.32%) met the clinical criteria compatible with acute lung injury. All 6 patients had prompt recovery. Significant risk factors for hypoxemia were age, obesity, reduced cardiac function, previous myocardial infarction, emergency surgery, baseline chest radiograph with alveolar edema, high creatinine level, prolonged CPB time, decreased baseline PaO2-FIO2, use of dopamine after discontinuation of CPB, coronary artery bypass grafting, use of left internal mammary artery, higher pump flow requirement during CPB, increased level of hemoglobin or total protein content, persistent hypothermia 2 and 6 hours after surgery, requirement for reexploration, event requiring reintubation, and chest radiograph with alveolar edema 1 hour after surgery. Six hours after surgery, a lower PaO2-FIO2 ratio correlated significantly with time to extubation and lung injury. CONCLUSIONS: This study shows that despite improvements in the technique of CPB, hypoxemia depicted by low PaO2-FIO2 ratios is common in patients after CPB. It is short lived, however, and has minimal effect on the postoperative clinical course of these patients.

Early behavior signs of psychiatric phenotypes in fragile X syndrome.

Whether preschool males with fragile X syndrome can be distinguished from those with idiopathic developmental delay in the four problem behavior areas associated with the fragile X phenotypes was examined. Males with fragile X (n = 41) and age- and IQ-matched controls (n = 16) were rated by their mothers on the Dimensions of Temperament Scale-Revised, the Child Behavior Checklist, and the Aberrant Behavior Checklist--Community. The fragile X group showed deficits in motor skills, increased initial avoidance, decreased social withdrawal, deficits in attention, increased hyperactivity, and positive mood. They were distinguished from controls on all of these variables except hyperactivity and attention. When maternal characteristics were controlled for, the fragile X group showed a significantly higher level of generalized activity level than did controls.

Alveolar macrophages fat stain in early diagnosis of fat embolism syndrome.

The aim of this study was to assess the contribution of bronchoalveolar lavage (BAL) in the diagnosis of fat embolism syndrome (FES). The presence of fat droplets in alveolar macrophages was addressed in 13 trauma patients with bone fractures and 10 non-trauma patients with acute respiratory distress syndrome (ARDS). The control group was composed of 5 anesthesized patients with ischemic heart disease, immediately prior to cardiac surgery. Two patients with suggestive clinical and laboratory signs of FES had 40% and 24% fat-containing alveolar cells, respectively. The trauma patients without signs of FES displayed a wide variation in the percentage of fat-containing macrophages (from 3% to 95%). Most of the patients with ARDS who were receiving lipid emulsion as part of their parenteral nutrition, had a high percentage (> 85%) of fat-containing macrophages. Patients with normal lungs had no fat-containing macrophages. Our findings suggest that BAL Oil Red O-positive macrophages are frequently observed in trauma patients irrespective of the presence of FES. Therefore, estimation of the percentage of fat-containing macrophages from BAL is an unreliable marker of FES.

Conceptualizing and scaling the developmental structure of behavior disorder: the Lifetime Alcohol Problems Score as an example.

We contrast the current, clinically based framework for behavior disorder against a life course framework, as an alternative structure upon which to map the variations in onset and stability of clinical symptomatology known to take place in adult life. This alternative developmental framework is used as a base around which to understand known variations in rates of alcohol abuse/dependence over the life course and to review existing schemes for the evaluation of developmental variation in "caseness." From this work, it was proposed that symptom structure be regarded as a mass of greater or lesser breadth, with properties of extensiveness in time and life course invasiveness, as a function of where in the life course the symptomatology first emerged, and the degree to which the mass sustained itself in developmental time. This framework guided the construction of a time-based measure of alcohol related symptomatology, called the Lifetime Alcohol Problems Score (LAPS). The LAPS discriminated among a variety of alcohol-specific and nonalcohol-specific measures of alcohol-related difficulty, including diagnosis of alcohol dependence, having been in treatment, level of other psychopathology, and measures of family disorganization. The measure has potential applicability for prospective studies, and in estimating clinical prognosis. The utility of the paradigm as a framework within which to conceptualize the emergence, ebb, and flow of other behavior disorders is also discussed.

Time spent with child and parental agreement about preschool children's behavior.

Although there is a common core of agreement in parental perceptions of their preschool-age sons' problem behavior, perceptions of 107 parents became more concordant as fathers increased the amount of time they spent with their sons. At least within the context of a sample who were at risk for developing abuse of alcohol or other substances and antisocial behavior, fathers who spent less time with their sons perceived them to be less troubled than mothers perceived them to be.

Regulation of adenylate cyclase in E. coli.

The intracellular concentrations of cAMP in Escherichia coli are regulated mainly by control of the activity of adenylate cyclase. Withdrawal of the carbon source from the growth medium causes a gradual reduction of cellular energy and a dramatic stimulation of cyclase activity. Manipulations of the proton gradient at the cell membrane of ATP synthase-deficient E. coli (unc-) revealed that this part of the energy compartment is not responsible for the starvation-induced stimulation of cyclase. Neither is the ATP pool involved in regulation of the activity of the cyclase. The intracellular concentrations of ATP were experimentally lowered by purine starvation of auxotrophs, by inhibition of purine synthesis using amethopterin, or by affecting ATP synthesis using arsenate. None of these conditions led to stimulation of cyclase activity. The control of cyclase is exerted not via the energy pools but via uptake systems of energy substrates independent of whether the substrate can be metabolized or not, or how the transport is energized. The stringent coupling between these transport systems and cyclase activity enables the cell to react instantaneously to changes in its environment.

Control of phosphoenolpyruvate-dependent phosphotransferase-mediated sugar transport in Escherichia coli by energization of the cell membrane.

The phosphoenolpyruvate-dependent phosphotransferase-mediated sugar transport in Escherichia coli is inhibited by the energized of the membrane. This was shown in intact cells as well as in membrane vesicles. Relaxation of the proton gradient by uncouplers stimulated the uptake of sugars via the phosphotransferase system in aerobically cultured cells. No such effect was seen in anaerobic cells, apparently because the cell membrane of these cells is poorly energized. Energization by respiration of D-lactate or ascorbate inhibited the phosphotransferase uptake system in membrane vesicles. This inhibition was reversed by the addition of cyanide. Oxamate, a specific inhibitor of lactate dehydrogenase, prevented the inhibitory effect of D-lactate. Membrane vesicles prepared from a cytochrome-less mutant were not energized by D-lactate oxidation and the phosphotransferase uptake system was not inhibited.