Intravenous immunoglobulin may lessen all forms of infection in patients receiving allogeneic bone marrow transplantation for acute lymphoblastic leukemia: a pediatric oncology group study

Fifty patients with refractory acute lymphoblastic leukemia underwent allogeneic bone marrow transplantation after conditioning with high-dose cytosine arabinoside and fractionated total body irradiation. Twenty-nine received intravenous immunoglobulin (i.v.Ig) infusion, primarily to prevent cytomegalovirus infection, and 21 did not. The two groups were biologically comparable. Seven (24.5%) of the i.v.Ig-treated and 14 (66.7%) of the non-i.v.Ig-treated patients developed systemic viral, fungal or bacterial infections and/or interstitial pneumonitis (p less than 0.005), which were fatal in three and 12 cases respectively (p less than 0.001). Currently, 23 (79.3%) of the 29 i.v.Ig-treated and eight (38.1%) of the 21 non-i.v.Ig-treated patients are alive and well (p less than 0.01). We conclude that prophylactic i.v.Ig infusions may reduce the frequency of all forms of serious infection in patients with acute lymphoblastic leukemia undergoing allogeneic marrow transplantation, and thereby improve their survival expectation.     

Topographical distribution of absolute alpha-power in the EEG and psychopathology in schizophrenic outpatients

In 36 schizophrenic outpatients (Research Diagnostic Criteria) under neuroleptic maintenance treatment the EEG was recorded under resting conditions. The absolute alpha-power (7.5-13 Hz) was estimated by Fast Fourier Transform as the mean of 300 2-second epochs for the leads F3/A1, F4/A2, 01/A2 and 02/A2. Two lateralization quotients (anterior, posterior) and two anteriorization quotients (left, right) were calculated from the absolute alpha-power. Clinical status was assessed cross-sectionally with BRPS, GAS and CGI. The main findings are: 1) A linear relationship between the left/right ratio of absolute alpha-power over posterior regions and anxiety/depression--the more the alpha-power is left-lateralized, the higher the anxiety/depression score; 2) a curvilinear, inverted U-shaped relationship between the left/right ratio of absolute alpha-power over posterior regions and the score of schizophrenia-specific symptomatology; 3) the amount of daily neuroleptic dose (mgCPZ) has no impact on EEG-parameters. Results are discussed with respect to hemisphere asymmetry models of psychopathology.     

Longitudinal in vivo effects of growth hormone overexpression on bone in transgenic mice.

In this study we examined the effect of systemic overexpression of GH on bone in transgenic mice longitudinally in vivo over a period of 9 months. We observed substantially increased BMC in GH transgenic mice and a significant reduction in serum osteocalcin. GH effects on bone were strongly dependent on gender and developmental stage. INTRODUCTION: State-of-the-art bone marker and microimaging technology was applied in this longitudinal study to examine bone metabolism, BMC, bone density, and cortical bone structure over the life span of growth hormone (GH) transgenic (tg) mice. MATERIALS AND METHODS: Thirty-eight mice from four genetic groups (male, female, tg, and controls) were examined with DXA, and their femur and tibia were examined with peripheral QCT (pQCT). Osteocalcin (formation) and collagen cross-links (resorption) from serum and urine were also measured at postnatal weeks 3, 6, 9, 12, 18, 26, and 38. RESULTS: GH tg mice displayed a significant increase in body weight (up to 50%) and BMC (up to 90%), but serum osteocalcin was significantly reduced compared with controls. GH tg females (but not males) displayed increased trabecular density over controls up to week 12. In contrast, male (but not female) GH tg mice displayed a higher cortical cross-sectional area than controls. Cortical density was significantly lower in both male and female GH tg mice compared with control mice. CONCLUSIONS: The increase in BMC in GH tg mice is associated with reduced serum osteocalcin levels, indicating that bone turnover may be lower than in the control mice. On a structural level, bone responds to GH excess in a gender-specific manner, with alterations varying substantially between different developmental stages.     

Kidney Transplantation Substantially Improves Endothelial Progenitor Cell Dysfunction in Patients with End-Stage Renal Disease

Endothelial progenitor cells (EPC) are involved in endothelial repair and maintenance. Dysfunction of EPC may contribute to accelerated arteriosclerosis in chronic kidney disease. Kidney transplantation (KTx) improves both survival and endothelial function of dialysis patients. In a prospective study, we tested to which extent KTx changes EPC biology. We studied number and function (migratory activity, adhesion to extracellular matrix proteins and to mature endothelial cells [EC]) of EPC in 20 patients during dialysis and 3, 6, 9 and 12 months after KTx. Twenty-two healthy volunteers served as matched controls. Circulating precursor populations were measured by flow cytometric analysis. Cytokines relevant for EPC mobilization were monitored. Compared to the dialysis state, KTx increased the migration of EPC to approximately 2-fold. Adhesion to fibronectin and to collagen type IV was significantly increased after KTx. An improved adhesion rate of EPC to mature EC was observed. The number of EPC decreased. The amount of precursor populations showed no difference compared to the pretransplant state. Our study shows an improved function of EPC after KTx. This finding indicates an improved potential for endothelial repair which in turn may contribute to enhanced endothelial function and reduced cardiovascular morbidity after KTx.     

Monitoring motor function during resection of tumours in the lower brain stem and fourth ventricle

Objectives Even in the days of modern microsurgery, the removal of a brain stem lesion remains a surgical challenge. Especially when operating on children, the prognosis is directly related to the radicality of the resection; however, a radical resection is often associated with surgical morbidity. Intraoperative neuromonitoring could help to minimise the surgical morbidity, but few studies have been performed to clarify the value of this monitoring. We investigated a prospective series of 21 patients with lesions involving the brain stem for the prognostic value and benefits of neuromonitoring.Methods We performed intraoperative neuromonitoring of cranial nerve function by electromyography (EMG) and motor evoked potential (MEP). The results were correlated with postoperative neurological deficits.Conclusions There is a good correlation between intraoperative neurophysiological events and postoperative neurological deficits in patients with lesions of the brain stem. In general, transient, prolonged, spontaneous activity in EMG is associated with a transient paresis of the respective muscle, whereas a permanent spontaneous activity is associated with a permanent deficit. Intraoperative neuromonitoring reliably predicts postoperative neurological function in patients with tumours of the lower brain stem and fourth ventricle. This neuromonitoring guides the neurosurgeon in the operation and may decrease surgical morbidity. We recommend using monitoring of MEP and EMG of the lower cranial nerves in surgery on all patients with lesions involving the lower brain stem and fourth ventricle.     

High concentrations of soluble tumor necrosis factor receptors in ascites.

Ascites and plasma concentrations of soluble tumor necrosis factor receptors p55 and p75 were measured in a prospective study in 34 patients (35 occasions of ascites) with hepatic (5 infected and 21 uninfected) and malignancy-related (9) ascites. All patients had high concentrations of both soluble tumor necrosis factor receptors in ascites and plasma; these were about 500 times higher than the corresponding tumor necrosis factor-alpha concentrations. Ascites levels of soluble tumor necrosis factor receptors p55 and soluble tumor necrosis factor receptors p75 were significantly elevated in patients with malignancy-related (p55: 26.0 +/- 8.6 ng/ml; p75: 20.5 +/- 17.4 ng/ml; mean +/- S.D.) and infected ascites (p55: 25.1 +/- 10.9 ng/ml, p75: 22.6 +/- 11.0 ng/ml) compared with patients with uncomplicated hepatic ascites (p55: 10.1 +/- 4.4 ng/ml; p75: 6.0 +/- 2.6 ng/ml). Patients with infected or malignancy-related ascites also showed higher soluble tumor necrosis factor receptor concentrations in plasma than did patients with plain hepatic ascites. Successful antibiotic treatment of peritonitis reduced soluble tumor necrosis factor receptor p55 and p75 ascites levels in three patients from 24.2 +/- 15.2 ng/ml to 10.7 +/- 1.9 ng/ml and from 20.2 +/- 14.4 ng/ml to 7.5 +/- 1.8 ng/ml, respectively. Soluble tumor necrosis factor receptors p55 and p75 at cutoff levels of 16.5 ng/ml and 9.5 ng/ml, respectively, differentiated between infected or malignant and plain hepatic ascites with diagnostic accuracies of 94% and 89%, respectively. They did not differentiate between infected and malignant ascites. The concentrations of soluble tumor necrosis factor receptor p55 were usually higher in ascites than in plasma in all subgroups of patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential modification of muscarinic cholinergic receptors in the hippocampus of patients with Alzheimer''s disease: an autoradiographic study

We have used quantitative light microscopic autoradiographic techniques to analyze changes in muscarinic cholinergic receptors in the hippocampus in Alzheimer type dementia (ATD). The density and distribution of muscarinic cholinergic receptors has been correlated with the density of neurons, neuritic plaques and neurofibrillary tangles in the CA1 subfield of the hippocampus of control and ATD patients. The number of pyramidal cells per mm² in the CA1 sector was significantly decreased in ATD cases as compared to controls, although there were large variations among cases. The most marked reductions in cell counts were observed in patients with a history of profound dementia. The densities of muscarinic receptors, as well as the proportions of M₁ and M₂ subtypes, in the CA1 sector and dentate gyrus were not significantly different between ATD and old non-demented patients. Neuritic plaques, even in high numbers, did not affect the density of muscarinic receptors; moreover, the densities of receptors over the neuritic plaques did not differ from the surrounding neuropil. However, in some ATD cases there was a marked decrease in the concentration of these receptors in the CA1 sector and subiculum, with no change in the proportions of muscarinic receptor subtypes. These patients exhibited frequent extracellular remnants of neurofibrillary tangles (ghost tangles), but scarce neuritic plaques, and were those showing severe losses of pyramidal cells. There was a significant positive correlation between the total concentration of muscarinic receptors in the CA1 and the density of pyramidal cells, suggesting that decreases in receptor concentration result from a severe neuronal loss. We observed that the ratio of muscarinic receptors per pyramidal cell was significantly increased in ATD patients. This might indicate a possible upregulatory mechanism for muscarinic receptors in the population of remaining neurons in ATD. However, decreases of receptor numbers following severe neuronal fall out suggest that compensatory mechanisms are no longer possible in such cases. The question is raised whether these differences between cases reflect different diseases or different stages of the same disease.     

Natural oocyte retrieval with intravaginal fertilization: a simplified approach to in vitro fertilization.

To simplify in vitro fertilization (IVF), we have combined natural-cycle oocyte retrieval with intravaginal fertilization. Our subjects ranged in age from 28-40 years and were monitored by ultrasound and steroid hormone levels. Oocyte retrieval was carried out under vaginal ultrasound-guided aspiration 32-36 hours after the onset of the LH surge. The oocyte was identified and placed in a sealed capsule containing culture media and sperm. The capsule, in a sealed cryoflex envelope, was placed in the woman's vagina and removed 42-48 hours later. The embryo was then isolated and transferred to the woman's uterus. Fifty-one retrieval cycles were attempted in 45 patients. At least one oocyte was retrieved in 88% of cycles, and fertilization was achieved in 84% of oocytes. Of the five clinical pregnancies (10%), four have delivered and one is ongoing. The cost of this procedure is approximately one-third that of standard IVF. The advantages of our method are the elimination of the use of gonadotropins, the simplicity of monitoring and oocyte retrieval, and the lack of need for expensive laboratory equipment. Natural oocyte retrieval with intravaginal fertilization may prove appropriate for those women requiring IVF who fear multiple pregnancies, have side effects from controlled ovarian hyperstimulation, or cannot afford standard IVF.     

Contribution of striate cortex and the superior colliculus to visual function in area MT, the superior temporal polysensory area and the inferior temporal cortex

We studied the visual responses of single neurons in three extra-striate visual areas of the macaque following lesions of striate cortex, lesions of the tecto-pulvinar system or both. After striate lesions, there was (a) considerable specific activity remaining in area MT including direction selectivity, (b) only non-specific activity in the superior temporal polysensory area (STP), and (c) no visual responsiveness at all in inferior temporal cortex (IT). In animals with striate lesions, interruption of the tecto-pulvinar pathway eliminated the residual visual activity in MT and STP that survived the striate lesions. Interruption of the tecto-pulvinar pathway alone had little or no effect on visual evoked activity in any of the three areas. These results are related to the relative dependence of visual responsiveness in MT, STP and IT on striate cortex and the superior colliculus, to differences between the dorsal and ventral cortical processing streams, and to neural mechanisms underlying blind sight.