Fatigue and the wear-off effect in adult patients with common variable immunodeficiency.

Patients with common variable immunodeficiency (CVID) have increased fatigue compared with the general population. Fatigue is associated with lower quality of life (QoL), which is associated with higher mortality in CVID. This study aimed to determine the prevalence of self-reported fatigue for patients with CVID and to identify its possible drivers and burden on QoL. We analysed data from the 2013 Immune Deficiency Foundation (IDF) treatment survey. Answers were included from 873 CVID patients who responded (respondents). Of the 873 respondents included in the analysis, 671 (76·9%) reported fatigue, of whom 400 (83·7%) were receiving intravenous (i.v.) immunoglobulins (IVIG) and 271 (68·6%) were receiving subcutaneous (s.c.) immunoglobulins. This difference in fatigue between patients receiving IVIG and SCIG was statistically significant (P < 0·001). Dose and frequency of immunoglobulin replacement therapy (IgGRT) did not affect fatigue prevalence. Fatigued patients on IVIG reported greater infection rates and required more anti-microbials during the wear-off period. Fatigued patients reported worse health status than non-fatigued patients, and had lower rates of employment, education, household income and school attendance than their non-fatigued counterparts. Fatigue is increased in CVID, especially among patients receiving IVIG, compared to SCIG. Fatigue has a significant impact on QoL and productivity in patients with CVID. Further studies to identify the mechanisms of fatigue are warranted to help advance therapeutic measures to treat this disease and improve patients' QoL and wellbeing.

Latent therapeutic demand model for the immunoglobulin replacement therapy of primary immune deficiency disorders in the USA.

BACKGROUND AND OBJECTIVES: Our research aim is to model latent therapeutic demand (LTD) for the immunoglobulin replacement therapy (IgGRT) of primary immune deficiency disorders (PIDDs) in the USA. Given the high level of variability of IgGRT use and major differences among American and European practices in the management of patients with PIDDs, we develop a USA-specific LTD model for common variable immune deficiency (CVID), hyper IGM syndrome, severe combined immune deficiency, Wiskott-Aldrich syndrome and X-linked agammaglobulinemia (XLA). METHODS AND MATERIALS: We use decision analysis methods to model the underlying IgGRT demand for PIDDs by assessing USA-specific epidemiology and treatment. Data for the epidemiology and treatment variables were obtained from the medical literature, USIDNET and Immune Deficiency Foundation. The uncertainty surrounding the variables was modelled using probability distributions and evaluated using Monte Carlo simulation. RESULTS: The mean treatment dose from USIDNET and European Society for Immunodeficiencies (ESID) was significantly different for treating CVID, and the number of annual infusions from USIDNET and ESID was significantly different for treating CVID and XLA. The mean and standard deviation of LTD for all PIDDs is 105·1 ± 88·5 g per 1000 population, with CVID contributing the most to LTD. CONCLUSION: Estimating country-specific LTD is important to ensure an adequate supply of IgGRT and an optimal treatment for patients with PIDDs and for improving national healthcare policymaking and production planning.

Role of antiseptics in the prevention and treatment of infections in nursing homes.

Inadequate infection control, wound care, and oral hygiene protocols in nursing homes pose challenges to residents' quality of life. Based on the outcomes from a focus group meeting and a literature search, this narrative review evaluates the current and potential roles of antiseptics within nursing home infection management procedures. We examine contemporary strategies and concerns within the management of meticillin-resistant Staphylococcus aureus (MRSA; including decolonization regimes), chronic wound care, and oral hygiene, and review the available data for the use of antiseptics, with a focus on povidone-iodine. Compared with chlorhexidine, polyhexanide, and silver, povidone-iodine has a broader spectrum of antimicrobial activity, with rapid and potent activity against MRSA and other microbes found in chronic wounds, including biofilms. As no reports of bacterial resistance or cross-resistance following exposure to povidone-iodine exist, it may be preferable for MRSA decolonization compared with mupirocin and chlorhexidine, which can lead to resistant MRSA strains. Povidone-iodine oral products have greater efficacy against oral pathogens compared with other antiseptics such as chlorhexidine mouthwash, highlighting the clinical benefit of povidone-iodine in oral care. Additionally, povidone-iodine-based products, including mouthwash, have demonstrated rapid in-vitro virucidal activity against SARS-CoV-2 and may help reduce its transmission if incorporated into nursing home coronavirus 2019 control protocols. Importantly, povidone-iodine activity is not adversely affected by organic material, such as that found in chronic wounds and the oral cavity. Povidone-iodine is a promising antiseptic agent for the management of infections in the nursing home setting, including MRSA decolonization procedures, chronic wound management, and oral care.

Amino acid influx across the mucosal border of the rat intestine in vivo.

The lack of an in vivo method for measuring influx of amino acid into the mucosa has prevented a systematic comparison of characteristics of amino acid influx in vivo with prior in vitro studies. We developed and validated a technique for measuring amino acid influx in vivo. The mucosa is exposed briefly to labelled amino acid perfused luminally at a rapid rate and tissue uptake is measured. The brief exposure period insures that amino acid is confined to the segment. The rapid perfusion rate minimizes concentration of endogenous Na+ in the lumen and permits Na-dependency for alpha-aminoisobutyric acid influx to be demonstrated in vivo for the first time. We also demonstrated the inhibitory effect of K+ and competition by glycine on alpha-aminoisobutyric acid influx in vivo. The saturation kinetics for L-leucine in vivo and in vitro were compared under varying perfusion rates and with and without stirring with air. Under optimal conditions of agitation (rapid perfusion and bubbling with air), the apparent Michaelis constant (Kt) is decreased to be almost equal to that determined under comparable influx conditions in vitro. These studies demonstrate no major difference between characteristics of amino acid transport under more physiologic in vivo conditions as compared with prior in vitro studies.

Effects of vanadate on water and electrolyte transport in rat jejunum.

The effect of vanadate (orthovanadate, VO4-) on water and ion transport was studied in rat jejunum. Water transport was tested by single-pass perfusion in vivo and ion fluxes by the Ussing-chamber technique in vitro. The results suggest that vanadate has two actions on ion and water transport: At low concentrations (10(-4) M) it causes Cl-, Na+ and water secretion by stimulation of adenylate cyclase; At higher concentrations (10(-3) and 10(-2) M) it decreases net absorption of Na+ and Cl- by inhibition of (Na+ + K+)-ATPase.

Alanine influx across serosal border of Testudo graeca intestine.

The influx of alanine across the serosal membrane of Testudo graeca intestinal cells with preserved epithelial orientation was examined. Our results suggest that: 1. The mechanism of alanine influx across the serosal membrane of turtle intesintal cells is a carrier-mediated process that has the characteristics of facilitated diffusion. 2. Alanine influx mechanism is independent of intra- and extra-cellular changes in Na+ and K+ concentrations, and is not altered by reversal of Na+ and K+ gradients across the serosal membrane. 3. In Na+-free media the mechanism of transport of alanine at the mucosal membrane has the same pattern of competitive inhibition by amino acids as the serosal.

Characteristics of the amino acid transport system in the mucosal border of rabbit ileum.

The specificity of the neutral amino acid transport system in the brush border was examined by studying the ability of amino acid analogues to inhibit the unidirectional influx of phenylalanine from mucosal solution into the cells. Effects were evaluated in terms of the affinity of various substrates for the amino acid site in the transport system. The affinity of amino acids for the site was proportional to the number of carbon atoms in the side chain. Electron-withdrawing substituents in the ring of phenylalanine increased affinity and electron-releasing groups decreased affinity. Removal of the alpha-amino group from phenylalanine decreased affinity by a factor of approximately 50 and removal of the carboxyl group decreased affinity 12-fold. Effects on affinity of variations in the side chain of the amino acid can be comparable in magnitude to that of the carboxyl group. The effect of sodium ion on the transport system appears to be similar for all compounds tested.

Sodium movement in high sodium feline red cells.

The transport of Na in the cat red cells has been studied under various experimental conditions. The unidirectional radioactive Na influx increased with increasing temperature until it reached a maximum value at 37 degrees C +/- 2 degrees C and then decreased with a further increase in temperature. Errors stated in this paper represent 1.0 standard errors of the mean. The apparent activation energy was calculated in the region between 25 and 37 degrees C and was found to be 4.9 +/- 0.5 kcal/mole. Copper at a concentration of 0.04 mM inhibited this influx by 65%. When cells were suspended in isosmotic KCl buffer, cell volume was found to decrease initially with time. This unusual behavior is discussed in terms of Na to K preference of the cell membrane. In cat red cells, Na influx was found to increase about 13-fold when cell volume was decreased from 1.16 normal to 0.87. This effect could not be reproduced when the medium osmolarity was changed only by the addition of urea, a permeating molecule. On the other hand, K influx was found to decrease from 0.24 +/- 0.03 mEq/liters RBC, hr at a relative cellular volume equal to 1.0 to 0.11 +/- 0.01 mEq/liters RBC, hr at a cell volume of 0.75. Na influx in human red cells did not show any significant dependence on cell volume. The properties of Na movement in the cat red cells are compared to those of human red cells.

The sodium-alanine interaction in rabbit ileum. Effect of sodium on alanine fluxes.

The model of the interaction between Na and alanine at the mucosal border of rabbit ileum has been tested further by examining the efflux of alanine from the cells toward the mucosal solution. Alanine efflux shows a tendency toward saturation as cellular alanine concentration increases and is influenced by cellular Na concentration. A decrease in cell Na concentration causes an increase in the apparent Michaelis constant with little change in maximal efflux rate. Studies on strips of mucosa treated with ouabain or cyanide showed that the direction of net alanine transfer between the cells and the medium is determined by the direction of the Na concentration difference. The cells extrude alanine against a concentration difference when cell [Na] exceeds medium [Na] and accumulate alanine when cell [Na] is less than medium [Na]. The observations are consistent with the model previously suggested involving a transport site that combines with and translocates both Na and alanine, and with the concept that the Na concentration difference between mucosal solution and cytoplasm provides at least part of the energy for active transport of alanine.

The sodium-alanine interaction in rabbit ileum. Effect of alanine on sodium fluxes.

The interaction between Na transfer and alanine transfer across the mucosal border of rabbit ileum has been studied further by examining the effect of alanine on Na movement. Studies on strips of mucosa treated with ouabain showed that net Na movements against a Na concentration difference could be caused by a concentration difference of alanine. Na extrusion from mucosal cells was demonstrated when cellular alanine concentration exceeded that in the external medium. Conversely, the cells took up Na against a concentration difference when external alanine concentration was greater than cellular concentration. Unidirectional Na efflux from the cells toward the mucosal solution was increased by loading the cells with alanine. The relation between the increment in Na efflux and alanine efflux was approximately that predicted by the model of Curran et al. (reference 2) for the Na-alanine interaction at the mucosal border of the cells. The results offer further indication that the transport system is reversible and symmetrical.

Alanine efflux across the serosal border of turtle intestine.

The exit of alanine across the serosal border of the epithelial cells of turtle intestine was measured by direct and indirect techniques. A decrease or an increase in cell Na did not affect the amino acid flux from cell to serosal solution. Cells loaded with Na and alanine did not exhibit any extrusion of alanine when their serosal membranes were exposed to an Na-free medium containing alanine. However, substantial amino acid extrusion was observed across the mucosal cell border under similar conditions. Although alanine flux across the serosal membrane appeared to be Na-independent, it showed a tendency toward saturation as cellular alanine concentration was elevated. The results are consistent with the postulate that the serosal and mucosal membranes of intestinal cells are asymmetrical with respect to amino acid transport mechanisms. The serosal membrane appears to have an Na-independent carrier-mediated mechanism responsible for alanine transport while transport across the mucosal border involves an Na-dependent process.

Ambulatory radical retropubic prostatectomy.

OBJECTIVES: To review the experience of 40 consecutive patients who underwent radical retropubic prostatectomy and to determine if and how the procedure could be performed safely on an ambulatory basis. METHODS: Between June 20, 1994 and November 26, 1996, 40 consecutive men with clinically localized prostate carcinoma underwent radical retropubic prostatectomy. Retrospective data regarding the patient population, patient satisfaction, clinical outcome, and length of hospitalization were evaluated. RESULTS: The average age for the patients was 62.6 years (range 44 to 75) with an average PSA of 10.44 ng/mL. Eighty percent (32 of 40) of the patients were discharged on postoperative day 1, 17.5% (7 of 40) were discharged on postoperative day 2, and 2.5% (1 of 40) were discharged on postoperative day 7. The average operative time was 89.5 minutes (range 65 to 135), measured from the time of incision to completion of closure. The organ-confined rate was 80% (32 of 40). The continence evaluated at 6 months was 90.9% (30 of 33). The potency at 4 months was 35% (10 of 28) and at 1 year was 55.6% (10 of 18). Postoperative complications were minimal, with 7.5% (3 of 40) bladder neck contractures and 2.5% (1 of 40) wound infections. Patient satisfaction assessed by questionnaires revealed that 90% (36 of 40) thought that the length of hospitalization was adequate and 97.5% (39 of 40) would choose to have the procedure again. A second series of 15 patients have also undergone radical retropubic prostatectomy utilizing a pelvic block to expedite discharge. Of these 15 procedures, 10 were performed on an ambulatory basis. CONCLUSIONS: Radical retropubic prostatectomy can be performed expediently with the maintenance of patient satisfaction, continence rates, potency rates, recurrence rates, complication rates, and pathologic results. The advantage to such an approach is expedited patient discharge, cost savings to the medical system, and no alteration in patient recovery or clinical outcome, such as organ-confined rate, potency, and continence. In this series, the majority of patients were discharged on postoperative day 1. On the basis of this experience, we have performed the procedure on an outpatient basis, while maintaining the same high quality of care. To date, 10 patients have undergone ambulatory radical retropubic prostatectomy and were discharged the same day of surgery without complications.

Flow cytometric and genetic study of familial gonadal tumors.

Three cases of familial gonadal tumors are reported. Genetic studies were conducted in 2 cases: a brother and sister with embryonal carcinoma and a benign cystic teratoma, respectively, and a father and son with embryonal carcinoma. DNA flow cytometry of paraffin-embedded tumors and constitutional karyotyping were performed. Further genetic studies are emphasized.

The nonspecific nature of the vanadate inhibition of rat ileal (NA,K)-ATPase.

Vanadate has been suggested as an intracellular regulator of (Na+ + K+)-ATPase. To test this hypothesis we examined the stimulatory and inhibitory effects of vanadate on 86--Rb efflux and influx (measurements of the activity of the Na-pump) in rat ileum under conditions of normal, reduced and increased (Na+ + K+)-ATPase activity. The half maximal stimulation of the Rb efflux and the half maximal inhibition of the Rb influx were not different in the three conditions tested. This suggests that vanadate does not have a regulatory effect on the activity of the Na-K-transport enzyme. The vanadate effect seem rather, to be nonspecific in terms of being unrelated, on a mole per mole basis, to the activity of the (Na+ + K+)-ATPase enzyme.

Calcium-prostaglandin aggregation and its effect on prostaglandin uptake by isolated rabbit intestine.

A quantitative estimate of the role of calcium ions on the lipid--water partition coefficients of prostaglandin E1 and dinoprost suggested the possibility of prostaglandin molecules and calcium ions aggregating in a 14:1 ratio to produce a lipid-soluble aggregate. The aggregation is postulated to be a characteristic of prostaglandin molecules as compared to simple fatty acids, e.g., 1-octanoic acid, which, in the presence of calcium, behave differently than the prostaglandins. The uptake of prostaglandins by the mucosal surface of the rabbit intestine increased in the presence of calcium. For example, at 25 mM calcium, prostaglandin E1 was transported at approximately twice the rate as in the system containing no calcium. The uptake rate of dinoprost was estimated to be three times faster with 10 mM calcium than in the absence of calcium. Therefore, it is proposed that a carrier-mediated diffusion process, for both the prostaglandin molecules and calciumi ions, takes place in the uptake mechanism. Diffusion coefficients ranging from 0.48 X 10(-5) to 7.19 X 10(-5) cm2/sec and permeability coefficients ranging from 1.04 X 10(-2) to 15.6 X 10(-2) cm/sec were estimated for all systems studied.

Alanine transport across in vitro rabbit vagina.

Transmural flux of alanine across the vaginal epithelium of the rabbit is a specialized mechanism. There is a net serosal to mucosal translocation of the amino acid in the absence of a concentration gradient. Changes in reproductive cycle do not influence this mechanism but, in castrated animals, it is abolished. Transport properties of vaginal epithelium is important because of increasing utilization of intravaginal contraceptives.

[Surveillance of nosocomial infections related to anesthesia. A multicenter study]. / Surveillance des infections nosocomiales liées à l'anesthésie. Etude multicentrique.

OBJECTIVES: To determine incidence rate, main characteristics and risk factors of nosocomial infections associated with anesthesia (NIAA). STUDY DESIGN: Prospective, descriptive multicentre survey. PATIENTS: All patients aged more than 15 years and undergoing surgery (except cardio-thoracic, ENT or ambulatory surgery) under general or regional anaesthesia. METHODS: Voluntary participation of surgical units from public or private hospitals. Use of pre-established definitions of infections and a 72 hours postanesthetic follow-up. Anaesthesia and operation related risk factors collected. End point based on occurrence, or not, of clinical infection. Record, control, treatment and analysis of the data by Epi Info--5.0 software. Statistics used: Fischer's exact test, Mantel-Haenszel test, Anova method, Kruskall-Wallis test. RESULTS: Among 7,300 patients belonging to 13 hospitals, 25 developed an infection (nine vascular catheter related infections, 12 respiratory tract infections, two infections of the eye and two of the mouth). Only two infections have been bacteriologically documented. The overall incidence of NIAA was 3.4 per 1,000 patients. It was significantly higher after an anaesthetic of more than 2 hours and after transfusion. CONCLUSIONS: This first prospective survey of NIAA confirmed that nosocomial infections are a real problem in the practice of anaesthesia and the necessity to use preventive measures. A survey with a larger sample size would allow to specify the respective part of the various risk factors and to develop a risk index.

[Technical requirements for buying a heat and humidity exchanger for ventilation during anesthesia. French Society of Anesthesia and Intensive Care]. / Clauses techniques pour l'achat d'un filtre échangeur de chaleur et d'humidité destiné à la ventilation en anesthésie. Société française d'anesthésie réanimation.

To prevent cross infection and to improve the management of anaesthetic circuits, the French society of anesthesia and intensive care recommended the use of heat and moisture exchange filter (HMEF). Buying a HMEF needs a procedure with different steps and a product request form must delineate precise needed requirements of the device. In the absence of standardized methods to assess filtration performance, required specifications are established from both manufacturer data and scientific published studies. Proposed purchasing method and criteria help the health care workers at the time of final decision for objective comparison between the different devices on the market.

[A rare cause of obstruction of the intubation tube]. / Une cause rare d'obstruction de la sonde d'intubation.

A case is reported of endotracheal tube obstruction due to impaction of a turbinate. This complication occurred during a first attempt of nasotracheal intubation in an ASA 1 18-year-old patient. Once the tube had been inserted into the trachea, manual ventilation was impossible. The diagnosis was made on removal of the completely obstructed tube. Differential diagnosis was sudden severe bronchospasm or a herniated cuff. Anaesthesiologists should be aware of this rare complication when carrying out nasotracheal intubation. Means of prevention are proposed.

[Cerebral pneumocephalus after epidural anesthesia: a rare complication?]. / La pneumatocèle cérébrale après anesthésie péridurale: une complication rare?

A case is reported of pneumoencephalus occurring after an accidental dural puncture during a cervical epidural puncture using the loss of resistance technique. Six ml of air were injected intrathecally. The patient recovered spontaneously within five days. This complication may occur more frequently than commonly admitted. It may be difficult to differentiate between headache due to pneumoencephalus and that by stretching of the meninges due to cerebrospinal fluid leakage. Only a CT scan can help to answer this question.