Collecting and evaluating convalescent plasma for COVID-19 treatment: why and how?

Plasma provided by COVID-19 convalescent patients may provide therapeutic relief as the number of COVID-19 cases escalates steeply worldwide. Prior findings in various viral respiratory diseases including SARS-CoV-related pneumonia suggest that convalescent plasma can reduce mortality, although formal proof of efficacy is still lacking. By reducing viral spread early on, such an approach may possibly downplay subsequent immunopathology. Identifying, collecting, qualifying and preparing plasma from convalescent patients with adequate SARS-CoV-2-neutralizing Ab titres in an acute crisis setting may be challenging, although well within the remit of most blood establishments. Careful clinical evaluation should allow to quickly establish whether such passive immunotherapy, administered at early phases of the disease in patients at high risk of deleterious evolution, may reduce the frequency of patient deterioration, and thereby COVID-19 mortality.     

A cut above the rest: Trimming as a painless depilatory

Shaving and other modes of epilation can cause undue anxiety, pain, or skin irritation in children. Here, we present hair trimming as a safe, painless, and cost‐effective alternative for patients with unwanted hair which may be performed indefinitely or until the child is old enough to direct management. In select cases, removing unwanted hair using this technique may facilitate dermatologic surveillance.     

Clinical Spectrum of Capillary Malformation–Arteriovenous Malformation Syndrome Presenting to a Pediatric Dermatology Practice: A Retrospective Study

Capillary malformation–arteriovenous malformation syndrome (CM‐AVM) is an autosomal dominant disorder caused by RASA1 mutations. The prevalence and phenotypic spectrum are unknown. Evaluation of patients with multiple CMs is challenging because associated AVMs can be life threatening. The objective of this study was to describe the clinical characteristics of children presenting with features of CM‐AVM to an academic pediatric dermatology practice. After institutional review board approval was received, a retrospective chart review was performed of patients presenting between 2009 and 2012 with features of CM‐AVM. We report nine cases. Presenting symptoms ranged from extensive vascular stains and cardiac failure to CMs noted incidentally during routine skin examination. All demonstrated multiple CMs, two had Parkes Weber syndrome, and two had multiple infantile hemangiomas. Seven patients had family histories of multiple CMs; three had family histories of large, atypical CMs. Six had personal or family histories of AVMs. Genetic evaluation was recommended for all and was pursued by six families; four RASA1 mutations were identified, including one de novo. Consultations with neurology, cardiology, and orthopedics were recommended. Most patients (89%) have not required treatment to date. CM‐AVM is an underrecognized condition with a wide clinical spectrum that often presents in childhood. Further evaluation may be indicated in patients with multiple CMs. This study is limited by its small and retrospective nature.     

Late, Painful, Subungual Hyperkeratosis in Incontinentia Pigmenti

Abstract: The postpubertal appearance of subungual, painful keratotic tumors is a rare feature of incontinentia pigmenti. A patient affected by incontinentia pigmenti developed subungual, painful, nontumoral, hyperkeratotic lesions of the hands at 10 years of age. The mildness of the subungual lesions may be explained by the early stage of the disorder, but it is difficult to correlate the severity of the fingertip pain with the absence of true tumoral swelling. To our knowledge this is the youngest patient reported so far and the only one with a prepubertal expression of this puzzling disorder.     

Histamine-operated calcium channels in intestinal smooth muscle of the guinea-pig

The effects of Bay K 8644 and of nifedipine on histamine-induced mechanical and electrical responses were studied in the longitudinal smooth muscle of the ileum and in the taenia coli isolated from the guinea-pig. Nifedipine (10(-9)-10(-7) M) depressed the tonic and phasic components of histamine contraction. Phasic tension was less sensitive to nifedipine inhibition than was tonic tension (I50: 27 +/- 6 and 2.6 +/- 0.4 nM respectively). Bay K 8644 (10(-8)-10(-7) M) increased tension and rhythmic activity of intestinal smooth muscle and potentiated the histamine responses. The phasic tension evoked by histamine 10(-5) M and the phasic tension evoked by the KCl depolarizing solution showed the same sensitivity to nifedipine inhibition (I50: 28 +/- 5 nM) and were similarly potentiated by Bay K 8644. The tonic tension in response to the KCl-depolarizing solution was more sensitive to nifedipine inhibition than was the tonic tension in response to histamine and was not potentiated by Bay K 8644. These results indicate that different Ca entry pathways, dependent or not on modification of the membrane potential, are involved in the contractile response evoked by histamine in intestinal smooth muscle.     

Phytochelatin production by marine phytoplankton at low free metal ion concentrations: laboratory studies and field data from Massachusetts Bay.

Phytochelatins are small metal-binding polypeptides synthesized by algae in response to high metal concentrations. Using a very sensitive HPLC method, we have quantified phytochelatins from phytoplankton in laboratory cultures at environmentally relevant metal concentrations and in marine field samples. Intracellular concentrations of phytochelatin, in the diatom Thalassiosira weissflogii, exhibit a distinct dose-response relation with free Cd2+ concentration in the medium--not with total Cd(2+)--and are detectable even when the free Cd2+ concentration is less than 1 pM. In Massachusetts Bay, phytochelatin levels (normalized to chlorophyll a) in the particulate fraction are similar to those measured in laboratory cultures exposed to picomolar free Cd2+ concentrations and exhibit a decreasing seaward trend. Incubations of natural samples with added Cd2+ confirmed the induction of the peptides by this metal. Ambient phytochelatin concentrations thus appear to provide a measure of the metal stress resulting from the complex mixture of trace metals and chelators in natural waters.     

Examination of the role of the colloids hydroxyethylstarch, dextran, human albumin, and plasma proteins in a modified UW solution.

The delayed contralateral nephrectomy procedure (three-step) produced inconsistent results, indicating that the preserved autotransplanted kidney tends to remain unfunctional and to regenerate incompletely unless the demand for work is placed upon it. Omission of HES in UW (UW-plain) did not affect preservation success, but resulted in increased graft edema. Substitution of HES in UW with plasma (SGF-V) or albumin (MAlb) gave significantly worse results than UW-like solutions with or without synthetic colloids. Replacement of HES in UW with UMdex-70 or UMdex-500 gave nonsignificantly worse results than UW-like solutions with or without synthetic colloids. The use of UMdex-40 as the main colloid in UW cheapened the solution, equalled the preservation success of UW and UW-plain but surpassed UW-plain in edema prevention, and exceeded UW concerning recovery of graft microcirculation.     

Superoxide production by peripheral blood monocytes during sustained endotoxaemia in sheep.

1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2-) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min-1 kg-1). 2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy. 3. O2- generation by isolated monocytes was measured by the O2- dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2- production was significantly (P = 0.008) higher for non-survivors (31.3 +/- 8.8 nmol 30 min-1 10(-6) cells; n = 4) than for survivors (6.2 +/- 2.3 nmol 30 min-1 10(-6) cells; n = 7). 4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2- production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2- production with opsonized zymosan. 5. These results suggest that (1) increased O2- production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2- production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.