Serial magnetic resonance imaging and neurophysiological studies in multiple sulphatase deficiency.

We present serial clinical, magnetic resonance imaging (MRI) and neurophysiological findings of a patient with multiple sulphatase deficiency (MSD), who was first admitted at the age of 9 months, because of psychomotor retardation. MRI demonstrated extensive diffuse symmetrical high signal in the deep white matter of both cerebral hemispheres, as well as of the subcortical white matter and the brainstem, while there was additional enlargement of sulci and subdural spaces and mild atrophy. Assay of arylsulphatase A activity in white blood cell homogenates at the age of 29 months disclosed a marked deficiency of the enzyme, compatible with the diagnosis of early-infantile metachromatic leukodystrophy. During the course of a later admission, the presence of ichthyosis pointed out to the possible diagnosis of MSD; further assays of sulphatases in plasma, leukocytes as well as in cultured fibroblasts, combined with an abnormal excretion of mucopolysaccharides and sulphatides in urine confirmed the diagnosis. Molecular analysis identified a homozygous disease-causing mutation (R349W) of the SUMF1 gene. Serial neurophysiological and MRI studies demonstrated the progressive nature of the disorder (regarding both central and peripheral nervous system), correlating with the clinical deterioration (spastic quadriplegia, optic atrophy and epilepsy) with subsequent death at the age of 4 years.     

The potentialities of some antihistaminics in preanaesthetic medication.

A detailed study has been carried out on the potentialities of antazoline and chlorpheneramine (C.P.M.) in preanaesthetic medication. It included a determination of their sedative action, effects on cardiovascular system and any possible anticholinergic and antiarrhythmic properties. Both drugs depressed spontaneous activity in mice. Antazoline produced hypotension in chloralosed dogs and spinal cats (a peripheral action). Both produced a negative inotropic action on isolated rabbit's heart. On rat's auricle antazoline produced a positive chronotropic action while C.P.M. produced a negative chronotropic action. Both drugs could protect the heart against adrenaline induced arrhythmias during chloroform and halothane anaesthesia. Their anticholinergic properties were demonstrated by studies on isolated rabbit's heart and intestine as well as on isolated guinea pig's ileum.     

Which bioengineering assay is appropriate for irritant patch testing with sodium lauryl sulfate?

For testing with sodium lauryl sulphate (SLS), measurements of transepidermal water loss (TEWL) and cutaneous blood flow with laser Doppler (LD) are considered to be the most reliable methods. The aim of this study was to determine which method of measurement should be preferred when conducting SLS testing under varying conditions. Patch testing with SLS at different concentrations and exposure times was performed. TEWL values were compared with those of LD. TEWL values showed distinct changes at low SLS concentrations and short application periods. By contrast, higher SLS concentrations were necessary to increase LD values. Short application of patches changed TEWL rather than LD values. When evaluating SLS patch testing by bioengineering methods, TEWL measurement appears to be more suitable for a test procedure that provokes mild skin reactions (SLS concentration <1%), whereas LD measurement is more appropriate to evaluate pronounced skin reactions (SLS concentration >or=1%).     

Persistent cough and failure to thrive: a presentation of foreign body aspiration in a child with asthma

Severe failure to thrive (FTT) in a child with asthma and a persistent cough should not be explained solely by asthma and warrants a thorough and prompt evaluation. The finding of a foreign body in our case was surprising, because it does not usually present as or lead to FTT. Good clinical judgment and habits could prevent the course of events that we described in this case. Following are the key lessons to be learned from this presentation: (1) maintain a high index of suspicion for foreign body aspiration, even in toddlers with asthma, (2) pay special attention to a child with FTT, (3) be aware of localizing findings on physical examination and chest radiographs, and (4) perform a chest radiograph no later than after 1 month of chronic cough.     

Efficacy of Intravenous Immunoglobulin in Neurological Diseases

Owing to its anti-inflammatory efficacy in various autoimmune disease conditions, intravenous immunoglobulin (IVIG)—pooled IgG obtained from the plasma of several thousands individuals—has been used for nearly three decades and is proving to be efficient in a growing number of neurological diseases. IVIG therapy has been firmly established for the treatment of Guillain–Barré syndrome, chronic inflammatory demyelinating polyneuropathy, and multifocal motor neuropathy, either as first-line therapy or adjunctive treatment. IVIG is also recommended as rescue therapy in patients with worsening myasthenia gravis and is beneficial as a second-line therapy for dermatomyositis and stiff-person syndrome. Subcutaneous rather than intravenous administration of IgG is gaining momentum because of its effectiveness in patients with primary immunodeficiency and the ease with which it can be administered independently from hospital-based infusions. The demand for IVIG therapy is growing, resulting in rising costs and supply shortages. Strategies to replace IVIG with recombinant products have been developed based on proposed mechanisms that confer the anti-inflammatory activity of IVIG, but their efficacy has not been tested in clinical trials. This review covers new developments in the immunobiology and clinical applications of IVIG in neurological diseases.     

Fc Glycan-Modulated Immunoglobulin G Effector Functions

Immunoglobulin G (IgG) molecules are glycoproteins and residues in the sugar moiety attached to the IgG constant fragment (Fc) are essential for IgG functionality such as binding to cellular Fc receptors and complement activation. The core of this sugar moiety consists of a bi-antennary heptameric structure of mannose and N-acetylglucosamine (GlcNAc), further decorated with terminal and branching residues including galactose, sialic acid, fucose, and GlcNAc. Presence or absence of distinct residues such as fucose and sialic acid can dramatically alter pro- and anti-inflammatory IgG activities which could be harnessed for immunotherapeutic purposes. Here we review recent advances in understanding the role of the IgG-Fc glycan during immune responses and for immunotherapy with a focus on sialic acid and intravenous immunoglobulin (IVIG) treatment.     

Integration of Precipitation Kinetics From an In Vitro,Multicompartment Transfer System and Mechanistic Oral Absorption Modeling for Pharmacokinetic Prediction of Weakly Basic Drugs

Solubility, dissolution, and precipitation in the gastrointestinal tract can be critical for the oral bioavailability of weakly basic drugs. To understand the dissolution and precipitation during the transfer out of the stomach into the intestine, a multicompartment transfer system was developed by modifying a conventional dissolution system. This transfer system included gastric, intestinal, sink and supersaturation, and reservoir compartments. Simulated gastric fluid and fasted state simulated intestinal fluid were used in the gastric and intestinal compartment, respectively, to mimic fasted condition. The new transfer system was evaluated based on 2 model weak bases, dipyridamole and ketoconazole. Traditional 2-stage dissolution using 250 mL of simulated gastric fluid media, followed by 250 mL of fasted state simulated intestinal fluid, was used as a reference methodology to compare dissolution and precipitation results. An in silico model was built using R software suite to simulate the in vitro time-dependent dissolution and precipitation process when formulations were tested using the transfer system. The precipitation rate estimated from the in vitro data was then used as the input for absorption and pharmacokinetic predictions using GastroPlus. The resultant simulated plasma concentration profiles were generally in good agreement with the observed clinical data, supporting the translatability of the transfer system in vitro precipitation kinetics to in vivo.     

The value of vacuum-assisted closure in septic patients treated with laparostomy

The ideal method of temporary abdominal closure (TAC) should allow rapid closure, easy maintenance, and wound repair with minimal tissue damage. The aim of this retrospective study is to compare open abdomen outcomes between patients managed with vacuum-assisted closure (VAC), and patients managed with other methods of TAC, when septic abdomen is present. Two groups of patients with septic open abdomen: 27 treated with VAC versus 31 treated with other techniques of TAC. We studied open abdomen duration, number of dressing changes, re-exploration rate, successful abdominal closure rate, overall mortality, and development of enteroatmospheric fistulas. The VAC device demonstrated its superiority concerning open abdomen duration (P < 0.001), number of dressing changes (P < 0.001), re-exploration rate (P < 0.002), successful abdominal closure rate (P < 0.0001), and development of enteroatmospheric fistulas (P < 0.00001). Compared with other methods of TAC, our experience with the VAC device demonstrated its advantages concerning clinical feasibility. The high rates of direct fascia closure with an acceptable rate of ventral hernias are further benefits of this technique.