Efficacy and safety of Gammaplex(®) 5% in children and adolescents with primary immunodeficiency diseases.

This open-label multi-centre study evaluated Gammaplex(®) 5%, a human intravenous immunoglobulin (IVIG) 5% liquid, in 25 children and adolescent patients (aged 3-16 years) with primary immunodeficiency diseases (PIDs). Subjects received Gammaplex 5% (at doses of 300-800 mg/kg/infusion) for 12 months, with a 3-month follow-up. The primary efficacy end-point was the incidence of serious acute bacterial infections (SABIs) during the 12-month treatment period. Secondary objectives assessed safety and tolerability. Nineteen males and six females were treated using the same infusion schedule as their prior IVIG treatment (14 and 11 subjects on 21- and 28-day dosing schedules, respectively). Two SABIs of pneumonia were reported, resulting in an annual SABI event rate of 0·09 [upper one-sided 99% confidence interval (CI) = 0·36]. Twenty-one subjects (84%) experienced ≥ 1 infection during the study, with a median infective episode per subject/year of 3·08 (range = 0-10·4). Sixteen subjects (64%) missed ≥ 1 day of nursery or school because of infection or other illness. All trough immunoglobulin G levels exceeded 7·00 g/l after 15 weeks (mean = 9·69 g/l; range = 7·04-15·35 g/l). Product-related adverse events occurred in 14 subjects (56%); none were serious. Of 368 total infusions, 97 (26%) were associated temporally with an adverse event (≤ 72 h after infusion), regardless of causality. Laboratory test results and adverse-reaction data showed no evidence of product-related haemolysis or thromboembolic events. These data demonstrate that Gammaplex 5% is effective in preventing SABIs and well tolerated in children and adolescents with PID.

Femoral Access-Site Complications with Tenecteplase versus Alteplase before Mechanical Thrombectomy for Large-Vessel-Occlusion Stroke.

BACKGROUND AND PURPOSE: IV thrombolysis with alteplase before mechanical thrombectomy for emergent large-vessel-occlusion stroke is associated with access-site bleeding complications. However, the incidence of femoral access-site complications with tenecteplase before mechanical thrombectomy requires exploration. Here, femoral access-site complications with tenecteplase versus alteplase before mechanical thrombectomy for large-vessel-occlusion stroke were compared. MATERIALS AND METHODS: All patients receiving IV thrombolytics before mechanical thrombectomy for large-vessel-occlusion stroke who presented from January 2020 to August 2022 were reviewed. In May 2021, our health care system switched from alteplase to tenecteplase as the primary thrombolytic for all patients with stroke, facilitating the comparison of alteplase-versus-tenecteplase femoral access-site complication rates. Major (requiring surgery) and minor (managed conservatively) access-site complications were assessed. RESULTS: One hundred thirty-nine patients underwent transfemoral mechanical thrombectomy for large-vessel-occlusion stroke, of whom 46/139 (33.1%) received tenecteplase and 93/139 (66.9%) received alteplase. In all cases (n = 139), an 8F sheath was inserted without sonographic guidance, and vascular closure was obtained with an Angio-Seal. Baseline demographics, concomitant antithrombotic medications, and periprocedural coagulation lab findings were similar between groups. The incidence of conservatively managed groin hematomas (2.2% versus 4.3%), delayed access-site oozing requiring manual compression (6.5% versus 2.2%), and arterial occlusion requiring surgery (2.2% versus 1.1%) was similar between the tenecteplase and alteplase groups, respectively (P = not significant). No dissection, arteriovenous fistula, or retroperitoneal hematoma was observed. CONCLUSIONS: Tenecteplase compared with alteplase before mechanical thrombectomy for large-vessel-occlusion stroke is not associated with an alteration in femoral access-site complication rates.

Outcomes of Mechanical Thrombectomy in the Early (<6-hour) and Extended (≥6-hour) Time Window Based Solely on Noncontrast CT and CT Angiography: A Propensity Score-Matched Cohort Study.

BACKGROUND AND PURPOSE: Current stroke care recommendations for patient selection for mechanical thrombectomy in the extended time window demand advanced imaging to determine the stroke core volume and hypoperfusion mismatch, which may not be available at every center. We aimed to determine outcomes in patients selected for mechanical thrombectomy solely on the basis of noncontrast CT and CTA in the early (<6-hour) and extended (≥6-hour) time windows. MATERIALS AND METHODS: Consecutive mechanical thrombectomies performed for acute large-vessel occlusion ischemic (ICA, M1, M2) stroke between February 2016 and August 2020 were retrospectively reviewed. Eligibility was based solely on demographics and noncontrast CT (ASPECTS) and CTA, due to the limited availability of perfusion imaging during the study period. Propensity score matching was performed to compare outcomes between time windows. RESULTS: Of 417 mechanical thrombectomies performed, 337 met the inclusion criteria, resulting in 205 (60.8%) and 132 (39.2%) patients in the 0- to 6- and 6- to 24-hour time windows, respectively. The ASPECTS was higher in the early time window (9; interquartile range = 8-10) than the extended time window (9; interquartile range = 7-10; P = .005). Propensity score matching yielded 112 well-matched pairs. Equal rates of TICI 2b/3 revascularization and symptomatic intracranial hemorrhage were observed. A favorable functional outcome (mRS 0-2) at 90 days was numerically more frequent in the early window (45.5% versus 33.9%, P = .091). Mortality was numerically more frequent in the early window (25.9% versus 17.0%, P = .096). CONCLUSIONS: Patients selected for mechanical thrombectomy in the extended time window solely on the basis of noncontrast CT and CTA still achieved decent rates of favorable 90-day functional outcomes, not statistically different from patients in the early time window.

Nerve growth factor triggers microfilament assembly and paxillin phosphorylation in human B lymphocytes.

Increasing evidence suggests that the nervous system is involved in allergic inflammation. One of the potential regulatory molecules of the neuroimmune system is nerve growth factor (NGF). Recent studies from our group demonstrated the presence of a functional NGF receptor (NGFR) on human B lymphocytes. Moreover, we showed that gp140trk tyrosine kinase, which serves as an NGFR, was involved in transduction of early signaling events in human B lymphocytes. The mechanisms by which NGF initiates the signaling cascade and the link between the neuroimmune systems are unknown. We have focused on the role of the cytoskeleton as a possible mediator for transduction of signals induced by NGF. Polymerized actin (F-actin) content was determined by fluorescent staining and immunoblotting with antiactin antibody. Addition of NGF caused a time- and concentration-dependent increase in F-actin content, and maximum effects were noted after 1 min. These increases in F-actin content and NGF-induced thymidine incorporation could be blocked by incubating the cells with cytochalasin D and botulinum C2 toxin before the addition of NGF. Incubation of human B lymphocytes with 10 nM K252a, an inhibitor of Trk kinase, decreased NGF-induced microfilament assembly by 75%. In immunoprecipitation experiments, addition of NGF to B cells induced a rapid increase in the tyrosine phosphorylation of paxillin, one of a group of focal adhesion proteins involved in linking actin filaments to the plasma membrane. Coimmunoprecipitation studies demonstrated the association between gp140trk kinase and paxillin. Together, these observations suggest that actin assembly is involved in NGF signaling in human B cells, and that paxillin may be essential in this pathway after phosphorylation by gp140trk kinase.

March myoglobinemia: a hazard to renal function.

Serum muscle enzyme levels, myoglobin levels, and renal function were measured in a group of 20 army recruits who had volunteered for a prolonged period of primary, specially designed, gradual training. Blood samples were taken before training and before and after each hike. Levels of serum myoglobin, creatinine phosphokinase, lactic dehydrogenase, and SGOT indicated muscle injury. Levels of urea creatinine, and uric acid and creatinine clearance evaluated renal function. Substantial elevation of muscle enzyme levels and persistent myoglobinemia were observed throughout the study. A highly significant decrease in creatinine clearance was demonstrated. After the last hike, the mean creatinine clearance was 70.41 mL/min, which is notably lower than the value at the beginning of the study. Prolonged physical exercise induces muscular damage, as evidenced by a rise in myoglobin and enzyme levels. Continuous muscle injury induces persistent myoglobinemia, a probable hazard to renal function.

[Validation of a multiplex PCR for detection of Shiga toxin-producing Escherichia coli]. / Validación de una técnica de PCR múltiple para la detección de Escherichia coli productor de toxina Shiga.

Shiga toxin-producing Escherichia coli (STEC) cause non-bloody or bloody diarrhea, hemorrhagic colitis and hemolytic uremic syndrome (HUS) in humans. The aim of the present study was to validate a multiplex PCR for the STEC diagnosis based on the detection of stx1, stx2 and rfbO157 genes. The multiplex PCR validation was carried out in two independent laboratories in a parallel way. Work range, selectivity and robustness were established. The PCR performance was evaluated using different concentrations of two STEC strains harboring different target genes. The work range depended on the strain analyzed, the maximum and the minimum values were 6.6 x 10(7) and 1.0 x 10(4) CFU/50 microl. The detection limit was 1.0 x 10(4) CFU/50 microl and the cut limit 1.0 x 10(5) CFU/50 ml. A good robustness was observed when different variables were introduced. Inclusivity, exclusivity, positive predictivity, negative predictivity and analytical accuracy were of 100%. Interference was not shown when different concentrations of STEC strains, carrying different genes, were used. The validated technique is an appropriate alternative for detection and confirmation of STEC O157 and non-O157 strains from bacterial cultures.

Benefit of ketotifen in patients with eosinophilic gastroenteritis.

PURPOSE: Eosinophilic gastroenteritis (EG) is a rare condition of unknown etiology characterized by vomiting, diarrhea, protein-losing enteropathy, and eosinophilic infiltration of the gastrointestinal mucosa. The potential association of EG with allergy and related mast-cell release of mediators led us to evaluate the ability of an antihistamine drug to modify the course of the disease. PATIENTS AND METHODS: Six patients with protracted gastrointestinal symptoms were diagnosed with EG because of histologic evidence of predominantly eosinophilic infiltrates in the gastrointestinal mucosa. Each patient was treated in an open trial for 12 months with ketotifen (Zaditen), an antihistamine of the H1 class that is known to stabilize mast cells. RESULTS: All six patients improved clinically; four also gained weight. Total serum IgE levels decreased after 4 to 6 months of therapy. Clearing of eosinophilic infiltrates was documented in the four patients who underwent follow-up mucosal biopsies. CONCLUSION: We conclude that ketotifen treatment represents a safe and effective alternative to traditional systemic corticosteroid therapy for treatment of EG.

Effect of erythropoietin treatment on nutritional status of continuous ambulatory peritoneal dialysis patients.

Seventeen patients--10 females, 7 males--mean age 52 years (range: 21-77 years), on CAPD for an average of 35 months (range 10-160 months) were studied. Mean initial dose of EPO was 114 +/- 45 U/kg/week subcutaneously (range: 59-209). The dose was adjusted to achieve and maintain a target Hb of 100 g/L and Hct 30%. Fifteen of the patients (88.2%) achieved this target within 6 months [baseline to month 6 changes: Hb 72 +/- 10 g/L to 107 +/- 12 g/L (p = 0.0001); Hct 22 +/- 3% to 33 +/- 4% (p = 0.0001)]. Serum total protein also increased significantly over the time of EPO use (p = 0.0133); changes from baseline were significant by the fourth month [68 +/- 9 g/L to 72 +/- 9 g/L (p = 0.0115)]. Serum albumin also increased significantly over time (p = 0.0157). The change from the baseline result (37 +/- 4 g/L) was statistically significant by month 2 (p = 0.0060) and was maintained over the following 4 months [month 6 result: 40 +/- 3 g/L (p = 0.0180)]. The increase was greater for 8 patients with initial serum albumin < 35 g/L (mean change 5.75 g/L) than for the 9 subjects with levels > 35 g/L (mean change 0.11 g/L). In a comparison group of 17 patients (matched for age, sex, duration of CAPD, underlying disease and antihypertensive treatment), who did not receive EPO treatment, albumin and protein did not appear to increase over time.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of erythropoietin on blood pressure in continuous ambulatory peritoneal dialysis patients.

To assess the effect of erythropoietin (EPO) treatment on blood pressure in continuous ambulatory peritoneal dialysis (CAPD) patients, we analyzed in a retrospective study the results of 6 months of EPO treatment in 17 CAPD patients. There were 10 females and 7 males, mean age 52 years, mean duration on CAPD 35 months. They received subcutaneously a mean initial EPO dose of 114 +/- 45 U/kg/week (range 59-209). This dose was adjusted throughout 6 months to achieve and maintain a target Hb of 100 g/L (Hct 30%). Seven of the patients were hypertensive before starting EPO treatment. Fifteen patients (88.2%) achieved the target hemoglobin. For all subjects (n = 17) there was a significant increase in lying mean blood pressure (MBP) from 93.8 +/- 10.0 to 105.2 +/- 14.4 mmHg (p = 0.0024). Four patients required an increase in their antihypertensive medication, and 4 were not treated before we started antihypertensive treatment (Group I). This group represents 46% (8/17) of the patients. There was no change in the antihypertensive medication status of the remaining 9 patients (Group II). The baseline lying MBP was not significantly different for the two groups (98.8 +/- 9.8 mmHg vs 96.1 +/- 7.2 mmHg). The mean weekly dose of EPO during the first 3 months was higher in Group I (126 vs 100 U/kg) and conversely was lower during the last 3 months (mean dose 108 vs 117 U/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Laparoscopically guided distal ventriculoperitoneal shunt placement.

In standard techniques for performing ventriculoperitoneal shunts, the peritoneal catheter is threaded more or less blindly into the peritoneal cavity. Using laparoscopic techniques allows accurate peritoneal placement, without a large incision, even in replacement procedures and in patients with previous abdominal operations. We performed 28 laparoscopically guided ventriculoperitoneal shunt placements and shunt revisions in 24 patients with hydrocephalus (aged 6-80 years). Sixteen of 24 patients (67%) had previous abdominal surgery. Laparoscopic shunt placement was successful in all patients. Mean operative time was 63 +/- 34.9 minutes (range 15-150 minutes). In 2 patients, broken and disconnected distal parts of previously inserted shunts were removed from the abdomen. One shunt was removed following infection and other one was revised due to shunt malfunction. Three patients required revision of the cranial part of the shunt. Laparoscopically guided distal ventriculoperitoneal shunt placement provides definite patient benefits: it allows shunt placement under direct vision, associated with reduced trauma to the abdominal wall, and avoids a consequent risk of intra-abdominal adhesions.

[Decreased interleukin-1 and interleukin-2 production after splenectomy].

Production of interleukin-1 and of interleukin-2 was measured in 57 splenectomized patients. 11 of them were after elective operations (aged 14-37 years, mean 24) and 46 posttraumatic (aged 20-36, mean 23) and in 20 appropriate controls. There was significant reduction of both interleukins in the splenectomized group, more evident in the elective group. The deficiency was not related to age of patient or time since splenectomy. These results support the view that a consequence of splenectomy is immunoregulatory deficit.

[Role of functional interaction between the facial and masticatory muscles in the genesis of synkineses in patients with neuritis of the facial nerve]. / Rol' funktsional'nogo vzaimodeistviia litsevoi i zhevatel'noi muskulatury v geneze sinkinezii u bol'nykh nevritom litsevogo nerva.

The electromyogram of orbicular muscles of the eye and masticatory muscles was studied in 19 patients with facial nerve neuritis and 11 normals. In a maximum contraction of the masticatory muscles, the orbicular muscles of the eye showed an activity equal to about 9% of the maximum amplitude of the orbicular muscles. Similar activity in the paretic muscles was not decreased. The development of secondary synkinesia is postulated.

[Trigeminal-facial reflex of the orbicularis orbis muscle in patients with flaccid paralysis of the facial musculature]. / Troinichno-litsevoi refleks krugovoi myshisy glaza u bol'nykh s vialym parezom litsevoi muskulatury.

With the aid of electric stimulation of the supraorbital nerve the authors studied the trigeminal facial reflex and evoked potentials of the facial nerve in patients with sluggish paresis of the facial muscles; 48 patients with neuritis of the facial nerve, 26 patients with polyradiculoneuritis, 5 patients with encephalitis and the syndrome of nucleus damage of the facial nerve (including 38 children) and 3 patients with myasthenia were studied. It is demonstrated that along with the equal extent of flaccidness of the facial muscles there are different characteristics of indices of the latent period and the amplitude of the trigeminal facial reflex, which are of diagnostic and prognostic significance.

The supraorbital approach: an alternative to traditional exposure for the surgical management of anterior fossa and parasellar pathology.

OBJECT: The use of a supraorbital craniotomy as a minimally invasive neurosurgical technique to treat pathology located in the anterior cranial fossa and parasellar region is reported. MATERIALS AND METHODS: 25 patients were operated upon using the supraorbital keyhole technique to expose various lesions located in the anterior skull base. Included were benign and malignant tumors, AVM, tuberculoma and trauma. DISCUSSION AND CONCLUSION: Utilizing small eyebrow incisions, a small supraorbital ("keyhole") craniotomy, and microneurosurgical and/or endoscopically assisted access, allowed us to gain excellent optimal and safe exposure to a number of different pathologies of the anterior base and parasellar regions. The lesions were resected under complete control and with full preservation of surrounding neurovascular structures.

Microfilament assembly is involved in B-cell apoptosis.

Crosslinking of the B-cell antigen receptor (BCR) initiates a chain of reactions which culminate in a number of biologic responses, including entry into the cell cycle or cell death. The signals and processes which lead to cell death are slowly being unraveled. Based on the dramatic changes in cell shape which occur during progression of the apoptotic response, activation of cytoskeletal assembly may be critical as this appears to be essential to the mitogenic response. In this study, we demonstrate that crosslinking of the human BCR with anti-IgM antibodies results in the rapid assembly of actin. Our data also suggest that this conversion of G- to F-actin may be a prerequisite for the apoptosis response, as prevention of this conversion by botulinum C2 toxin or cytochalasin D results in rescue of the cells from apoptosis. Prevention of tyrosine kinase activation, disruption of microfilament assembly, and rescue of B lymphocytes from apoptosis imply that tyrosine phosphorylation is needed for both microfilament assembly and apoptosis. In each instance where microfilament assembly is inhibited, anti-IgM-induced activation of the protease CPP32 (caspase) is also inhibited. Taken together, these results suggest that the microfilament system is actively involved in delivering signals for apoptosis.

A novel syndrome of combined immunodeficiency, autoimmunity and spondylometaphyseal dysplasia.

We describe here four patients who appear to have similar clinical and immunological features which constitute a novel syndrome. The patients present with short stature owing to spondylometaphyseal dysplasia and with severe infections as the result of a combined humoral and cellular immune deficiency. Presumably because of dysregulation of the immune system, all patients also developed autoimmune manifestations.

Epstein-Barr virus induces actin polymerization in human B cells.

The EBV selectively infects human and primate lymphocytes. This selective tropism occurs as a result of live virus infection through permissive membrane receptors. Once EBV has entered the cell, it induces proliferation and immortalization of these cells. The mechanism of EBV infection, however, remains largely unknown. We demonstrate here that a transforming strain, but not a nontransforming strain, of EBV stimulates the conversion of globular actin (G-actin) to filamentous actin (F-actin), a process that has been associated with activation and transformation of other cell types. Preincubation of B cells with botulinum C2 toxin or cytochalasin, which block the conversion of G-actin to F-actin, resulted in the inhibition of EBV-induced proliferation. These findings indicate that actin rearrangement is essential for infection of B cells by EBV.