Granulocyte colony-stimulating factor (G-CSF) dose-dependent efficacy in peripheral blood stem cell mobilization in patients who had failed initial mobilization with chemotherapy and G-CSF

For 10 consecutive patients in our unit who did not show a significant rise in blood progenitor cells within 14 days following chemotherapy and G-CSF, we increased the G-CSF dose from 5 to 10 microg/kg/day (n = 9) or from 10 to 15 microg/kg/day (n = 1). As a result, there were significant increases in total yield as well as yield per apheresis of mononuclear cells, CD34+ cells and CFU-GM (P < 0.025, <0.01 and <0.005, respectively). After G-CSF dose escalation, six of the 10 patients had sufficient CD34+ cells for performing transplantation. These results demonstrate a dose-dependent response of progenitor cell mobilization by G-CSF when used in combination with chemotherapy. Moreover, increasing the dose of G-CSF as late as the third week of mobilization may still provide sufficient cell yield even with patients who did not show a significant mobilization with conventional doses of G-CSF.     

Antibodies to beta 2-glycoprotein-I: urea resistance, binding specificity, and association with thrombosis

The aim of the present study was to evaluate the urea resistance and binding characteristics of anti-beta 2-glycoprotein I (anti-beta 2GPI) antibodies using standard anticardiolipin (aCL) and anti-beta 2GPI enzyme immunosorbent assays (ELISAs). Sera from patients with antiphospholipid syndrome (APS) (n = 22) and non-APS (n = 24), positive in a standard aCL ELISA, were tested in an anti-beta 2GPI ELISA performed in polystyrene-irradiated ELISA plates. Urea resistance aCL and anti-beta 2GPI ELISAs were performed by measuring the ability of antibodies to recognize antigen in the presence of 2 M urea. The serum dilution after urea treatment (D) expressed as a percentage of the serum dilution without urea treatment (D(o)) corresponding to the same optical density was defined as residual activity (RA = 100 D/D(o)). The higher the RA, the higher the resistance of the antibodies to urea. APS compared to non-APS sera had higher aCL binding (absorbance values ranging between 0.180 and 1.400; median, 0.717 vs 0.120-1.273; median, 0.250, respectively; P < 0.004). Six APS patients' sera had low aCL levels but they expressed RA > or = 30%. Anti-beta 2GPI antibodies were detected in 15 of 22 APS vs 3 of 24 non-APS patients (P < 0.03); RA > or = 30% was detected in 15 of 22 APS vs 1 of 23 non-APS patients (P < 0.004). Using a CL affinity column, antibodies were purified from three APS anti-beta 2GPI negative and three non-APS anti-beta 2GPI-positive patients and tested in a aCL ELISA, using highly purified bovine serum albumin (BSA) as a blocking agent (modified ELISA); reactivity was not detected in two APS and one non-APS sera. On the contrary, the reactivity of the purified antibodies was high when beta 2GPI was incubated with CL in the ELISA plates; thus some anti-beta 2GPI negative sera from APS patients recognized the CL/beta 2GPI complex, rather than CL or beta 2GPI alone. In conclusion, anti-beta 2GPI antibodies are common in the APS patients, but a number of such patients recognize the CL/beta 2GPI complex and not CL or beta 2GPI. Antibodies to either beta 2GPI or the CL/beta 2GPI complex derived from APS sera present a high resistance to urea. Anti-beta 2GPI antibodies of low urea resistance exist in a minority of non-APS patients with autoimmune disease.     

Evaluation of high-resolution CT and MR cisternography in the diagnosis of cerebrospinal fluid fistula

BACKGROUND & AIMS: Whether inflammation of the cardia indicates gastroesophageal reflux disease (GERD) and/or is a manifestation of pangastritis caused by Helicobacter pylori infection is unknown. The aim of this study was to evaluate the relationship between cardia inflammation, H. pylori infection, and cardia intestinal metaplasia in patients with and without GERD. METHODS: Patients with GERD were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the distal esophagus and cardia, fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: Neither the prevalence of H. pylori infection (controls, 48%; GERD, 41%) nor cardia inflammation (controls, 41%; GERD, 40%) differed between groups. All 11 controls and 22 of 23 patients with GERD (96%) and cardia inflammation had H. pylori infection. Esophagitis was more common among GERD patients (33%) than controls (7%; P = 0.01). Cardia intestinal metaplasia was more common among controls (22%) than GERD patients (3%; P = 0.01); all had cardia inflammation, 7 had H. pylori infection, and 6 had metaplasia elsewhere in the stomach. CONCLUSIONS: The prevalence of cardia inflammation is similar in patients with and without GERD and is associated with H. pylori infection (P < 0.001). Cardia intestinal metaplasia is associated with H. pylori-related cardia inflammation (P = 0.01) and intestinal metaplasia elsewhere in the stomach, indicating that it is distinct from Barrett's esophagus.     

In vitro studies on the use of clay, clay minerals and charcoal to adsorb bovine rotavirus and bovine coronavirus

Rotaviruses are the leading cause and coronaviruses are the major contributors of acute gastroenteritis in the young of various mammalian and avian species. Despite numerous trials and decades of research, vaccines have limited efficacy particularly for calves. As an alternative method of controlling infection, we have investigated broad spectrum antiviral agents that are not discriminatory among various viruses. This report involves testing a variety of adsorbent agents including charcoal, clay, and clay minerals to adsorb rotavirus and coronavirus in vitro. Results revealed that all the adsorbent agents had good to excellent capability of adsorbing rotavirus and excellent capability of adsorbing coronavirus. Percent adsorptions ranged from 78.74% to 99.89% for rotavirus and 99.99% for coronavirus; while sand (negative control) was < 0.01%. A high affinity binding was present as determined by a low percent desorption (0.06-3.09%). However, the adsorbent bound virus complex retained, and may have actually enhanced, infectivity.     

Extraorganic hepatic artery aneurysm: failure of transcatheter embolization

BACKGROUND: We evaluated the safety and efficacy of transurethral electrovaporization of the prostate (TVP) as a new alternative treatment for patients with benign prostatic hyperplasia. METHODS: A total of 22 patients with symptomatic benign prostatic hyperplasia, including 4 with urinary retention, underwent TVP. If enough of a cavity was not created after 60 minutes of vaporization, transurethral resection of the prostate (TURP) was performed successively. International Prostate Symptom Score (I-PSS) with quality-of-life index, maximum flow rate, and postvoid residual volume were measured at baseline and at 2 weeks, 1, 3, and 6 months. A pressure-flow study was performed at baseline and at 3 or 6 months after surgery. RESULTS: TURP was required in 10 of 22 patients. At 6 months, mean I-PSS decreased from 20.0 to 5.2, quality-of-life index decreased from 4.6 to 1.1, mean maximum flow rate increased from 6.9 to 16.7 mL/s, and postvoid residual volume decreased from 152 to 32 mL. Detrusor pressure at maximum flow decreased from 108 to 39 cm H2O, with a significant relief of bladder outlet obstruction in 93% of the patients. Mean decrease in hematocrit was 4.4%, and in serum sodium, 4.8 mEq/L. None of the patients required transfusions or had TUR syndrome. A urethral stricture and a severe stress incontinence developed in 1 patient. CONCLUSION: TVP seems to be a safe and effective alternative to a standard TURP associated with fewer intraoperative complications. Although preliminary clinical results have been promising, further study is necessary to establish long-term efficacy and safety of this procedure.     

Variations in uterine innervation during the estrous cycle in rat

Uterine innervation undergoes profound remodeling during puberty, pregnancy, and after parturition. However, the extent to which uterine innervation may change during the estrous cycle is uncertain. The objective of the present study was to determine whether nerve fiber density of the uterine horn is altered during the estrous cycle and, if so, which subpopulations are affected. Immunostaining for the pan-neuronal marker protein gene product (PGP) 9.5 revealed fibers within the vascular zone, myometrium, and endometrium, with greater density in the ovarian and cervical regions than in the middle. In most structures, nerve density was reduced during estrus. This could not be accounted for by increased target volume, as the reduction in longitudinal muscle innervation persisted after correction for changes in target size. Immunostaining for vasoactive intestinal polypeptide-immunoreactive parasympathetic nerves revealed fibers associated predominantly with the vascular zone and circular muscle within the cervical region. No cyclical variation was detected. Calcitonin gene-related peptide-immunoreactive nerves were present within all structures, and density was highest at the ovarian end. These fibers also did not vary significantly through estrous. Dopamine beta-hydroxylase-immunoreactive sympathetic nerves innervated all structures, with greater density in the ovarian end. These fibers were reduced substantially during estrus, but the decline was also significant in proestrus, thus preceding that detected by using the pan-neuronal marker. We conclude that the estrous cycle in rat is accompanied by structural remodeling of sympathetic nerves by way of retraction or degeneration of terminal fibers during estrus. The structural loss of the terminal axon apparently is preceded by depletion of catecholamine-synthesizing enzyme.     

Protein kinase C in platelets of depressed patients

Though described in 1769, the etiology of Zenker's diverticulum remains unclear. Various primary esophageal motor disorders have been proposed, but no consistent manometric pattern or anatomic etiology has been uniformly recognized. An association with clinical neurologic disease at our institution prompted a review of 12 cases of Zenker's diverticulum in patients over 60 years of age, treated in the last 8 years. Nine patients (75%) underwent cricopharyngeus myotomy and diverticulectomy, with uniformly good results. Ten patients (83%) had an associated neurologic disorder, substantiated by cranial CT or MRI, in most cases. A wide range of neurologic problems were identified, but a strong trend toward brainstem or basilar lesions was present. As expected, the etiology of the neurologic abnormality in most patients in this group was cerebrovascular disease, but two patients had peripheral neuropathies. We suggest that the etiology of Zenker's diverticulum in the elderly may be neurologic in origin. Esophageal motor disorders, including incomplete upper esophageal sphincter opening and increased hypopharyngeal pressures, which may result in Zenker's diverticulum, may be a manifestation of central or peripheral neurologic disease in the elderly.     

Shigella and the fluorinated quinolones

An 8-year-old girl presented with marked shortening of the right forearm due to destruction of both the radius and ulna secondary to neonatal osteomyelitis. A one-bone forearm operation was performed to achieve a stable forearm. Two years later, the one-bone forearm was lengthened for 6 months by callus distraction (callotasis) achieving 12 cm of extra length. The patient was last followed up at the age of 16. The appearance and functional outcome of the right upper limb had been improved and she was independent in all activities of daily living.     

Modulation of an early step in the secretory machinery in hippocampal nerve terminals

In hippocampal neurons, neurotransmitter release can be regulated by protein kinase A (PKA) through a direct action on the secretory machinery. To identify the site of PKA modulation, we have taken advantage of the ability of the neurotoxin Botulinum A to cleave the synaptic protein SNAP-25. Cleavage of this protein decreases the Ca2+ responsiveness of the secretory machinery by partially uncoupling Ca2+-sensing from fusion per se. This is expressed as a shift toward higher Ca2+ levels of the Ca2+ to neurotransmitter release relationship and as a perturbation of synaptic delay under conditions where secretion induced by the Ca2+-independent secretagogue ruthenium red is unimpaired. We find that SNAP-25 cleavage also perturbs PKA-dependent modulation of secretion; facilitation of ruthenium red-evoked neurotransmitter release by the adenylyl cyclase activator forskolin is blocked completely after Botulinum toxin A action. Together with our observation that forskolin modifies the Ca2+ to neurotransmitter release relationship, our results suggest that SNAP-25 acts as a functional linker between Ca2+ detection and fusion and that PKA modulates an early step in the secretory machinery related to calcium sensing to facilitate synaptic transmission.     

Brachial plexus injury during cardiac catheterisation in children. Report of two cases

The arm is particularly vulnerable to neurological injury, due to the intimate anatomical relationship between the brachial plexus and the traction zones. Severe injuries of the brachial plexus can be caused by compression, traction or laceration. Fortunately, many deficits are superficial and permanent neurovascular deficits are rare. Nevertheless, it is important to identify the probable cause of the injury since the prognosis for recovery directly depends on the underlying nature of the neurological deficit. Two anaesthetised children who suffered brachial plexus injury during cardiac catheterisation are reported. The first, with Ebstein's anomaly and significant pulmonary valve stenosis, presented, after the procedure, with a right arm motor deficit with proximal predominance. The second patient, with tetralogy of Fallot and pulmonary atresia, presented difficulty in left arm abduction and external rotation on awakening. The risk factors for brachial plexus lesions during anaesthesia are discussed. These include improper positioning, anaesthetic agents, extreme variations of body mass index and anatomical anomalies. Prevention, evolution and treatment of the brachial plexus injury are also considered. With proper care by the cardio-radiologist and anaesthesiologist the frequency of this injury can be reduced.