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.     

Fetal surgery in the head-neck area. Current status and new possibilities with the endoscope

Fetal surgery is defined as the intrauterine surgical correction of malformations that endanger the unborn child's life in prenatal stages of development or lead to death or severe damage of the child postnatally. Such surgery is a clinical reality now. Indications for intrataurine surgical procedures also exist for head and neck abnormalities, especially in the upper respiratory tract. These include exposure and temporary obstruction of the fetal trachea for correction of pulmonary hypoplasia in cases with congenital diaphragmatic hernias, prenatal tracheotomy in cases of laryngeal atresia for the correction of lethal pulmonary overdistension, and resection of embryonic tumors that obstruct the respiratory tract. The relatively high surgical risk resulting in particular from preterm labor occurring postoperatively may be reduced by employing minimally invasive techniques. Endoscopic procedures render opening of the uterus unnecessary and are of particular importance. In part of the procedures, only endoscopic surgery has led to therapeutic success rates justifying its clinical use. Further reduction of the operative risk suggests prenatal interventions, even in cases with non-lethal conditions. More diseases of the head and neck may thus be included in the spectrum of indications. One example is prenatal correction of a cleft lip and palate, which until now has only been performed in animal experiments. The particular characteristics of fetal wound healing allow this to take place without scarring up to a certain stage in pregnancy. This offers the prospect of a surgical correction that is invisible externally and avoids growth-impeding scars. The particular ethical and legal aspects of fetal surgery are discussed.     

Cytokines in rheumatoid arthritis: new therapeutic possibilities

The ingress of inflammatory leukocytes into the synovium is important for the pathogenesis of rheumatoid arthritis. Soluble inflammatory mediators regulate the inflammatory, chemotactic, adhesive, angiogenic events, as well as osteopenia associated with this disease. In this review authors discuss the role of a number of inflammatory mediators, such as cytokines, chemokines and growth factors in these processes. The outcome of arthritis is highly dependent on the imbalance between pro-inflammatory and anti-inflammatory mediators. Cytokine-related research also has important clinical relevance. Many of these proteins are detectable in the serum of rheumatoid patients and may eventually serve as useful laboratory markers of disease activity. Antirheumatic therapy currently used for the treatment of rheumatoid arthritis is often limited. Therefore, we need to consider alternative therapeutic regimens, such as the inhibition of cytokines and other soluble mediators, in order to prevent severe joint destruction. While there are many complex interactions involving cytokine networks and cascades in the arthritic joint, there are promising attempts to eliminate a single cytokine in clinical trials, such as ablation of tumor necrosis factor-alpha. Hopefully, the study of cytokines and their networks will lead to specific immunomodulatory therapies that will benefit rheumatoid patients by preventing joint destruction.     

Chronic orchialgia. A diagnostic and therapeutic hypothesis

OBJECTIVE: The objective of this study is to offer patients with chronic testicular pain and no physico-pathological finding, a likely cause not usually taken into account such as uricemia. The hypothesis of an intracanalicular deposit of uric crystals and/or the resulting alteration in nerve endings is suggested. METHOD: The study involved a total of 60 patients with chronic orchialgia and no detectable testicular pathology seen over a 5-year period. Mean age 35.6 years. They were all evaluated with routine laboratory tests, uricemia, uricosuria and in specific cases uroculture and Stamey's method. Orchidometry, vascular doppler and ultrasound were used in all cases. RESULTS: Presence of hyperuricemia was corroborated in 61.6% cases. Based on figures found, patients were divided into three groups. Patients were treated with a low-purine diet plus Allopurinol 300 mg/day, and symptoms receded in 81.06% cases. CONCLUSIONS: Due to the high incidence of hyperuricemia and the significant symptomatological relief obtained with specific treatment, we believe its determination should become routine.     

Right-sided diverticulitis: new diagnostic and therapeutic aspects

Because of its rarity in the Western World, diverticulitis of the ascending colon is often not taken into account in the differential diagnosis of abdominal pain in the right lower quadrant or is misdiagnosed as appendicitis. Of five patients who were treated for right-side diverticulitis in our hospital between April 1995 and April 1996, one underwent right hemicolectomy and one laparoscopic diverticulectomy. In three cases we succeeded with antibiotics alone. In three cases the diagnosis was made on the basis of CT-scan, prompted by peridiverticular changes. In one case the diagnosis was made at laparoscopy and confirmed by CT. In one case diagnosis and therapy were carried out only by laparoscopy. From the moment of diagnosis the average stay in hospital was twelve days and no complications occurred. During an average follow-up time of twelve months, all patients remained free of pain. On the basis of the case reports and a literature review we discuss the diagnostic value of CT and laparoscopy as well as the benefit of conservative therapy, which to us--in contrast to other authors--seems appropriate at least for the first bout of uncomplicated diverticulitis.     

A new cardiology patient simulator

The apolipoprotein E (APOE) epsilon4 allele is a risk factor in Alzheimer disease (AD), but not in vascular dementia (VaD). We have investigated whether the epsilon4 allele is more common in twin pairs concordant for AD, compared with those discordant for AD, and whether the epsilon4 allele is more common in AD twins than in VaD twins. In addition, we have investigated the relationship of the epsilon4 allele and the age at onset in AD and VaD. APOE genotype was analysed in 29 senile demented twin pairs. The epsilon4 allele was associated with AD and not with VaD. However, there was no difference in the frequency of the APOE epsilon4 allele in concordant (33.3%) and discordant (31.3%) AD dizygotic twin pairs. Age at onset in AD was significantly lower in epsilon4 homozygotes than in individuals with one or no copies of epsilon4 (62.4 vs. 73.5, p<0.01). In concordant AD twin pairs, the epsilon4 allele frequency was somewhat higher in the twins with earlier onset (41.7% vs. 25%), but the difference was not statistically significant. In the VaD group the age at onset was not significantly different between individuals with or without epsilon4 in their genotypes.     

Backache--orthopedic diagnosis and special therapeutic possibilities

Back pain is a wide-spread complaint in modern society and in part an adverse effect resulting from present-day lifestyles. To date, too little attention has been drawn to efficient prevention. The treatment of patients affected with back pain today calls for an in-depth pathophysiological knowledge about the mechanism occurring on the spine. Diagnostic methods and non-operative treatment have been complemented specifically by chirotherapeutic methods. A systematic classification of the vertebragenous pain syndromes and the related treatment strategies have proven to be successful. Irrespectively of that, the individuality of diagnosis and the complaint's progress in each patient should be taken into account at all events. Cost-intensive diagnostic imaging should only be undertaken with a clear indication. Today, the overwhelming majority of back pain patients undergo a non-operative treatment. In case the conservative applications prove inefficient, it is possible to successfully operate on patients a with disc prolaps, degenerative instabilities as well as osseous spinal foraminal stenoses. A precondition is a precise causal diagnosis and a clear indication for operative intervention.     

AIDS and opportunistic visceral mycoses. A diagnostic and therapeutic update

Candidiasis, cryptococcosis, aspergillosis, histoplasmosis, and coccidioidomycosis are the most commonly recognized visceral mycoses complicating the course of HIV infection and AIDS. Their current management issues are discussed on the ground of the personal experience, and the most recent literature evidences.     

Evidence of new diagnostic and prognostic human astrocytoma tumor markers. Potential therapeutic applications. II

Human astrocytic tumors grow into the normal brain parenchyma either as localized tumors, or as highly diffuse neoplasms. The diffuse phenotype relates to a specific sub-type of neoplastic astrocytes with a high motility and invasion capacity. Motility features refer to locomotion while invasion features refer to protease secretion. Our data reveal that several peptides belonging to the gastrin/cholecystokinin peptide class are able to significantly (and in certain cases very significantly) modify the level of tumor growth (at the level of cell proliferation and/or cell death), of motility and of invasion in various experimental models of human astrocytic tumors. We are synthesizing various gastrin/cholecystokinin-related peptides in order to develop clinical applications with which we want to inhibit astrocytic tumor growth, individual neoplastic astrocytic motility and the invasion of the normal brain parenchyma.     

Methods of investigation in clinical cardiology. X. Studies on the evaluation of diagnostic tests in cardiology

Diagnosis is a complex cognitive process which is characterised by uncertainty. This uncertainty can be managed through specific knowledge in conjunction with probability theory. Studies evaluating diagnostic tests are the best way of building this knowledge. Studies evaluating diagnostic tests have two essential components: the gold standard and the new test. Both components, gold standard and test, are independent measurement process that can be influenced by diverse sources of variability. The comparison between diagnostic and test is essentially a hierarchical procedure. Diagnostic tests are evaluated by their sensitivity, specificity compared to a definitive gold standard. The predictive values and the likelihood ratio test are also used. Sensitivity (the proportion of true positives) and specificity (the proportion of true negatives) are values obtained from a sample and thereby can be considered as the conditional agreement between gold standard and the new test. Kappa coefficients for sensitivity and specificity are useful tools for adjusting both indices. Sensitivity and specificity are non-poblational values, they are estimates of the true values of the study population and can be affected by random error and systematic errors (bias). Confidence intervals are useful for giving an indication of the precision of the point estimates of sensitivity and specificity. A suitable sound design is required to avoiding a biased estimate of sensitivity, likelihood ratio, and predictive values. Finally a list of potential biases is given with methods for minimising these.     

Acute life threatening catatonia--clinical significance and therapeutic possibilities

Malignant catatonia, associated with different somatic and psychiatric disorders, is a rare, life-threatening syndrome. Immediate recognition and adequate treatment are essential and may be life-saving. We describe a case of malignant catatonia and discuss the clinical implications. Additionally, we review the recent literature regarding epidemiology, nosology, current pathophysiological concepts, differential diagnosis, and treatment recommendations.     

Bone manifestations of multiple myeloma and therapeutic possibilities

In the text are summarized the results of studies dealing with supportive therapy of multiple myeloma bone disease. The similarities of primary osteoporosis and osteoporosis in multiple myeloma raised a hope that sodium fluoride will help to prevent or to slow down the osteoporotic process in multiple myeloma patients. The first studies in small groups of patients reported some advantage for the patients with sodium fluoride, later in randomized studies no benefit of sodium fluoride was confirmed. The effect of calcitonin was studied in small groups of patients. All studies confirmed analgetic effect and some of them proved positive effect on the amount of bone hydroxyapatite by a histomorphometric examination. The contribution of bisphosphonate to the therapy of myeloma patients was confirmed in extensive studies. With the exception of a Canadian study with ethidronate, all studies reported good analgetic effects and the inhibitory influence on bone destruction. The advantage of bisphosphonates in comparison to calcitonin is the possibility of p.o. administration or in i.v. periodical administration several times a year.     

Inflammation and bone metabolism in rheumatoid arthritis. Pathogenetic viewpoints and therapeutic possibilities

BACKGROUND: Systemic osteoporosis is a common and pathogenetically heterogenous complication in rheumatoid arthritis. Various factors such as disease activity, dosage and duration of glucocorticoid treatment and immobilization are involved in pathogenesis of osteoporosis in rheumatoid arthritis. INFLAMMATION AND BONE METABOLISM: Proinflammatory cytokines secreted by immunocompetent cells have a role in the regulation of the activity of osteoblasts and osteoclasts. The effects of these proinflammatory cytokines include the inhibition of bone formation and an increase in bone resorption. Interleukin-6 and nitric oxide induced in osteoblasts by proinflammatory cytokines are likely to be important mediators between these cytokines and the function of osteoblasts and osteoclasts. Furthermore, disease activity dependent changes in the secretion of glucocorticoids and in vitamin D metabolism may be involved in the pathogenesis of osteoporosis in this disease. Alteration of bone remodeling associated with immobilization is an important factor of systemic bone loss in rheumatoid arthritis. CONCLUSION: The inflammatory process in rheumatoid arthritis may cause penarticular and systemic bone loss by various cytokine and hormone mediated mechanisms. Concluding from these pathogenetic mechanisms, bisphosphonates and active vitamin D metabolites are likely to be effective therapeutic options in osteoporosis associated with rheumatoid arthritis.     

Thyroid cancer. Epidemiological, diagnostic and therapeutic features

This study presents a survey on the demand for out-patient neurological-neuropsychological rehabilitation. Neurologists working in acute care and in in-patient rehabilitation settings as well as neurologists and neuropsychologists with out-patient practice were asked to rate the demand for and the present means to realize out-patient neuropsychological rehabilitation. The results show a great demand for out-patient rehabilitation. The preferred concept and model of out-patient rehabilitation depends on the setting where the participants of the study work with a tendency to favour flexible programs close to patients' habitation.     

A new therapeutic model for integrating affect and cognition.

Reviews a model developed from social psychological research by I. Roseman et al (1990) that links appraisals and emotions, and discusses the model's therapeutic implications. The Roseman et al's model links the way in which individuals appraise a situation and their emotional reactions. The model can be easily used by therapists to intervene with clients to help them to understand how their emotions and their appraisals are interrelated. A 4-stage model for utilizing this appraisal model to work with individuals and couples on understanding and changing their appraisal patterns and their emotions is provided. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rhabdomyosarcoma in the area of the head-neck. A synopsis of some cases, therapeutic possibilities and prognoses

BACKGROUND: Soft tissue sarcoma represent approximately 7% of all neoplasms in children up to 14 years. The most common type (approx. 50%) among them is the rhabdomyosarcoma (RMS). Within the head and neck, which accounts for approx. 35% of all RMS, the tumor can be found ubiquitiously. Preferred localizations are the orbita, the paranasal sinuses, and the soft tissue of cheek and neck. The prognosis of RMS was formerly poor but has markedly improved since defined multimodal therapy was established in the Seventies (for example the Intergroup Rhabdomyosarcoma Study, IRS, in 1972; the International Society of Paediatric Oncology, SIOP, in 1975, or the German "Cooperative Weichteil-Sarkom-Studien", CWS, in 1981). The therapy of choice for RMS, according to the CWS, is chemotherapy because very often a good remission of the tumor is achieved. The main role of surgery is first to obtain biopsy specimens for histological diagnosis, and second aim is the complete resection of the primary and resectable metastases, for example by a neck dissection. Severe mutilation by radical surgery, especially in childhood, should be avoided in favor of multidrug chemotherapy and radiation in the interest of patient well-being. PATIENTS: Our retrospective study shows the treatment and results of 11 patients with a rhabdomyosarcoma of the head and neck within 25 years (1972-1997). RESULTS: Five of the 11 patients, who were treated in the years 1972-77, died (average 13 months, range 3-72 months). Five of the six patients, who were treated since 1991, have survived to date, one had a relapse of the tumor. Four special cases of patients are discussed in greater detail. CONCLUSION: Although the achieved mean survival time is encouraging nowadays (a 5-year survival rate of approx. 70% for all RMS is described) fatal cases are typical for this malignancy. Early diagnosis, localization, histological subtype, and prompt initiation of adequate treatment is decisive for a successful outcome.     

Pre-syncope and syncope at the operating table--diagnostic and therapeutic possibilities

OBJECTIVES: The aim of this study is to compare the initial experience at two different urologic centers of the 20 first laparoscopic nephrectomies performed either by transperitoneal laparoscopy (10 cases) in one center or by retroperitoneal laparoscopy (lumboscopy, 10 cases) in the other center. METHODS: 5 males and 15 females with a mean age of 36 years (range 3-74) were operated on the right side in 8 cases and on the left side in 12 cases. Nephrectomies were indicated in 18 cases for benign renal disease, and in 2 cases for ureteric tumor (1 patient in each group). The techniques of these two approaches are described. RESULTS: The mean operating time was shorter with lumboscopy (173 min) than with laparoscopy (210 min), probably due to the direct approach to the renal compartment without intraperitoneal dissection with lumboscopy. There were no severe intraoperative or postoperative complications, but one hematoma of the renal area in the laparoscopic group. The mean postoperative hospital stay was identical following lumboscopy and laparoscopy (4.3 and 4.2 days, respectively). CONCLUSION: These two approaches can be used to perform nephrectomy. In this initial experience, the results appear to be equivalent in terms of morbidity and postoperative hospital stay, but the operating time appears to be shorter with lumboscopy. Larger studies comparing respective nephrectomy conversion rates would provide other arguments in favor of one or other of these techniques.     

Quantitative-topographic and temporal characterization of myoelectrical activation patterns: new diagnostic possibilities in neurology, physiotherapy and orthopaedics

We previously reported that Chinese hamster ovary (CHO) cell lines overexpressing mutated human insulin receptors (hIRs) in which the tyrosine residues 1162 and 1163 were replaced by phenylalanines (CHO-Y2) exhibited a marked defect in hormone-induced receptor internalization as compared to CHO transfectants overexpressing wild-type hIRs (CHO-R). These two cell lines are now used to compare the role of tyrosines 1162-1163 in basal and ligand-stimulated receptor internalization as well as in receptor turnover. We show here that (1) in CHO-Y2 cells, basal endocytosis, like insulin-induced internalization, was markedly altered despite normal receptor turnover and (2) in both CHO-R and CHO-Y2 cells, basal receptor endocytosis was altered by tunicamycin, an inhibitor of protein N-glycosylation, whereas insulin-induced internalization was not. These results support a role for tyrosines 1162-1163 of the IR beta-subunit major autophosphorylation domain in both basal and ligand-stimulated receptor endocytosis and provide evidence that the two processes follow distinct pathways.