The role of intravenous immunoglobulin for the prevention and treatment of neonatal sepsis

Lesion of the entorhinal cortex in the adult rat is a model for Alzheimer's disease and produces a marked increase in acetylcholinesterase (AChE) activity in the outer molecular layer (OML) of the dentate gyrus. This has been attributed to the sprouting of cholinergic axons terminals in response to denervation of the OML. The aim of this study was to investigate the density changes of cholinergic terminals in the OML at the light microscope level by using choline acetyltransferase (ChAT) immunohistochemistry and quantitative analysis. The results showed that between days 10 and 33 after an entorhinal cortex lesion, there was a measurable increase in the density of ChAT-positive boutons in the OML of the ipsilateral dentate gyrus (x1.2-1.6 of contralateral). However, when shrinkage of the ipsilateral OML (x0.5-0.75 of contralateral) was taken into account, the apparent increase in ChAT terminal density was entirely accounted for by shrinkage of the OML. Thus ChAT immunohistochemistry at the light microscope level provides no positive evidence for a proliferation of cholinergic terminals in the entorhinal cortex lesion model. This is in agreement with previous biochemical assays that have shown no change of total ChAT activity in the dentate gyrus after entorhinal cortex lesions.     

Serum TNF levels in neonatal sepsis and septic shock

Tumor necrosis factor (TNF-alpha) has been implicated as a principal mediator in the pathogenesis of septic shock. TNF-alpha was measured by immunoradiometric assay in serum samples from 23 full-term infants with sepsis (15 with severe infection and 8 with septic shock) and in 20 healthy full-term newborns. Serum TNF-alpha levels were significantly higher in the group with sepsis, at the time of admission to the neonatal intensive care unit, than in the healthy neonates. The highest TNF levels were found in those newborns with septic shock, particularly in those who died. Although the method is far too slow for any clinical routine work, our results suggest that the presence of elevated serum TNF-alpha levels could be considered a sensitive and specific test for predicting septic shock and its clinical outcome.     

The significance of cytokines in the early diagnosis of postoperative intraabdominal sepsis]

The objective of the investigation was to evaluate the possible use of selected cytokines and cytokine receptors in the early diagnosis of postoperative intraabdominal sepsis. The investigation was focused on the dynamics of plasma levels of tumour necrotizing factor-alfa (TNFalfa), interleukin (IL)-1beta, IL-2, IL-6, IL-8, IL-10, soluble receptors IL-2 and IL-6 (sIL-2R and sIL-6R) and the receptor antagonist IL-1 (IL-1ra). The investigated parameters were tested on model operations (resection of large bowel and resection of pancreas). These two groups were compared with values recorded in patients with sepsis and with healthy subjects. Based on the assembled results the authors recommend to use for postoperative investigations the first 48 hours and to follow up the following parameters: IL-6, IL-ra or sIL-2R. During the first 48 hours these indicators differentiate sufficiently specifically incipient sepsis from an uncomplicated postoperative condition. During the subsequent period, i.e. more than 48 hours after surgery, it is useful to include in the examination pattern also some acute stage proteins (C reactive protein, alfa1-antitrypsin and haptalobin) which differentiate sepsis between the 3rd and 5th day after surgery.     

The value of technetium scintigraphy for early diagnosis and therapy of severe frostbite

Frostbites often present with a discrepancy between skin lesions and damage to deeper structures. 14 patients with the diagnosis of severe frostbite and/or hypothermia had been treated between 1990 and 1993. In addition to our standard approach including history, physical exam, and Doppler/Laser-Doppler studies, we performed technecium 99 scintigraphies in seven patients at three to five days after injury. In six patients (86%), there was an excellent correlation between scintigraphic and intraoperative findings. We conclude that early diagnosis and treatment of avital tissue reduces length of hospital stay and allows for maximum amputation stump length preservation.     

尿NAG在糖尿病肾病的早期诊断中的应用价值

目的:探讨尿NAG(UNAG)在糖尿病肾病的早期诊断中的应用价值.方法:本文根据2型糖尿病患者中HbA1c值将96例2型糖尿病患者分为血糖控制良好组(41例)和血糖控制不良组(55例),对比研究血糖控制良好组、血糖控制不良组及健康对照组的NAG/Cr和mALB/Cr水平.结果:两者异常率比较差异有显著性(X2=5.28,P<0.05).结论:尿NAG升高可作为糖尿病肾病的早期诊断指标之一.     

New diagnostic and therapeutic possibilities in neonatal sepsis

Neonatal sepsis remains a major clinical problem in neonatology, with high morbidity and mortality rates. The host defence against infections is immature in the newborn infant, and this makes the child more susceptible to invasive infection. The neutrophil storage pool and various granulocyte functions are impaired. In addition, the levels of immunoglobulins and complement are low. The detection of raised levels of complement activation products and cytokines may be of diagnostic help at an early stage of neonatal infection. Rapid treatment with antibiotics is essential for a favourable outcome. Possible adjuvant treatment may be to reduce the relative immunodeficiency by giving immunoglobulins or colony-stimulating factors which increase the production of leukocytes. Further, the potent inflammatory reaction initiated by the microorganisms may be suppressed by various therapies. In spite of much research in this field, no such adjuvant treatment has so far been shown to improve the outcome of neonatal sepsis.     

Effect of whole and fractionated intravenous immunoglobulin on complement in vitro

Intravenous immunoglobulins (IVIG) are increasingly used for treatment of inflammatory diseases, and the modulation of complement may contribute to some of its beneficial effects. IVIG may bind C1q and activated C3 and C4, and enhance inactivation of C3b. We have previously shown that IVIG inhibited complement-mediated lysis solely via its Fc part through interaction with the classical pathway. In the present study we have investigated whole IVIG (Octagam, and Sandoglobulin) and the monomer, dimer and multimer fractions of Octagam with respect to complement activation in serum and inhibition of complement lysis of red cells. The isolated fractions were found to be stable, homogeneous (monomer, dimer or multimer) and pure (virtually only IgG). Both whole IVIG and its fractions significantly activated complement in serum and inhibited hemolysis compared with human albumin. These effects were most pronounced in the monomer, less in the multimer and least in the dimer fraction. The complement activation was shown to be mediated through the classical pathway since formation of C1rs-C1inh complexes and C4bc were increased, in contrast to Bb. Surprisingly, heat aggregation of Octagam was not followed by a corresponding increase in complement activation, as would be expected, unless it was dialysed before heating, suggesting that it is stabilized to avoid excess activation. In conclusion, the results support the hypothesis that IVIG causes a mild activation of complement in vitro. We suggest that this effect may contribute to the complement inhibitory properties of IVIG by diverting complement deposition from the target to the fluid phase.     

Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma

Despite its predilection for multifocal growth and regional metastasis, papillary thyroid carcinoma (PTC) is a clinically indolent malignancy with an exceptionally favorable long-term prognosis. Together with the often striking inflammatory reaction present in PTC, its quiescent behavior has been suggested to reflect the activation of a tumor-induced immune response. To examine this possibility, we have studied the deposition of immunoglobulins and complement in PTC tissue. Samples from 70 cases of neoplastic and autoimmune thyroid diseases, including PTC (n = 41), follicular, anaplastic, and medullary carcinomas (n = 12), follicular adenoma (n = 6), Graves' disease (n = 8), and Hashimoto's thyroiditis (n = 3) were analyzed immunohistochemically. Cellular deposits of immunoglobulin G (IgG), particularly subclasses IgG1 and IgG4, and complement factors C3d, C4d, and C5 were shown in up to 80% of the PTC cases, whereas the other thyroid diseases studied showed little or no cellular deposition. Nonneoplastic tissue of PTC-containing thyroid glands (n = 22) lacked staining for IgG in 50% of the cases, and 82% were devoid of complement. The results suggest a tumor-specific immune response in PTC with activation of the classical complement cascade.     

The value of cerebrospinal fluid immunoglobulin analysis in clincial neurology

The IgG index (formula: see text) corrects for the influence of serum protein abnormalities as well as a bloodbrain barrier damage and is, therefore, a better measure for the presence of an IgG elevation in CSF due to IgG synthesis, when compared with other IgG quotients commonly used. Agar gel electrophoresis of CSF for demonstration of oligoclonal IgG is probably superior to the determination of the IgG index when a diagnosis of MS is suspected. Determination of kappa and lambda light chain antigenic determinants in CSF, and calculation of the kappa/lambda ratio may also be used to demonstrate the occurrence of oligoclonal CSF immunoglobulins. An abnormal ratio can, however, be demonstrated only in 50% of MS patients and has, therefore, at present no place as a routine diagnostic method when MS is suspected.     

Serum thyrotropin, prolactin, and growth hormone levels during the early neonatal period in the human infant

The purpose of this study was to evaluate the efficacy of a trapezoidal wave form for ventricular difibrillation. Overall efficacy showed the trapezoidal waveform to be effective for defibrillation, including patients weighing over 100 kg (220 lb). We concluded that (1) the trapezoidal waveform is an effective defibrillatory pulse and (2) the trapezoidal waveform offers pulse characteristics less deleterious than other established waveforms.     

Novel approaches to the prevention and therapy of neonatal bacterial sepsis

A variety of adjunctive treatments have been shown to offer potential benefits for neonates with sepsis. Most are not available clinically and those that are available still should be considered experimental or limited in their use; however, these efforts are far from complete and should continue to evolve in the coming years. Efforts toward the rapid diagnosis of bacterial infections are a necessary component in the eventual implementation of these potential novel strategies. As a better understanding of the intricate mechanisms of neonatal sepsis is developed, it will be possible to provide patients with an increasingly effective array of treatment and prevention strategies.     

The clinical observation of early neonatal pure breast-feeding

Through observation on the rate of physiological body weight loss, the percentage of body weight regaining and the incidence of infection in hospital of 160 newborns with rooming in and pure breast-feeding after uneventful delivery or caesarean section. The average rates of physiological body weight loss were 6.70% and 6.47% in pure breast-feeding group with normal delivery and caesarean section respectively, whereas 5.03% and 5.57% in mix feeding group. The percentage of body weight regaining at discharge were 34.00% and 53.33% in pure breast-feeding group compared with 11.46% and 40.00% in mix feeding group. The incidence of neonatal infection in hospital were 2.00% and 13.33% in pure breast-feeding group, instead 14.00% and 13.33% in mix feeding group. The results showed advantages and feasible of pure breast-feeding.     

Failure of intravenously administered immunoglobulin in the treatment of neonatal myasthenia gravis

Neonatal myasthenia gravis is uncommon and life threatening. We describe the use of intravenously administered immunoglobulin, in addition to conventional modalities, in a neonate with severe neonatal myasthenia gravis. However, despite this aggressive management, the child had a prolonged period of weakness requiring intensive care.     

Evaluation of risk factors for fatal neonatal sepsis

OBJECTIVE: To evaluate risk factors for fatal neonatal sepsis. DESIGN: Prospective study. SETTING: Referral neonatal unit of a teaching hospital. SUBJECTS: 171 neonates admitted with sepsis. METHODS: Clinical examination and investigations on the day of admission were recorded and the neonates followed up to determine the final outcome. RESULTS: The overall fatality was 48.5%. In the univariate analysis, the factors significantly associated with death were weight, gestational age, age at onset of sepsis, hypothermia, requirement of IPPV, presence of refractory septic shock, neutropenia, metabolic acidosis and raised prothrombin time. However, in the multivariate analysis, only neutropenia, metabolic acidosis, increased prothrombin time and refractory septic shock retained their significance. The adjusted odd's ratio (95% confidence interval) were 0.095 (0.04 = 0.22), 1.14 (1.04-1.25), 1.04 (1.002-1.08) and 11.82 (5.47-69.40), respectively. CONCLUSION: Even in a setting with high fatality rates, high risk of mortality in neonatal sepsis can be identified and targeted for intensive intervention.