Primary aspergillosis of the sphenoid sinus with pituitary invasion – a rare differential diagnosis of sellar lesions

Summary Aspergillosis belongs to the group of mycotic diseases of paranasal sinuses. The invasive forms, and particularly the fulminant forms, are potentially fatal. Isolated aspergillosis of the sphenoid sinus or the clivus is a difficult diagnosis, since the often misleading clinical manifestations of this rare disease develop late. These patients become apparent by neurological signs such as cavernous sinus syndrome, pseudotumor of the pituitary or the orbit. Diagnosis is often made intra-operatively or on histological examination. We report a case of invasive aspergillosis uniquely involving the sellar area revealed by clinical features suggesting a pseudotumor of the pituitary. Although such lesions are almost always seen in immune suppressed subjects, in our case, the patient was immune competent and had no past history of sinusitis. The question of whether, and when to perform limited or extensive surgery remains an issue for discussion, owing to the rarity of this disease honed by lack of experience. It depends on several factors: the kind of disease, the immunity, the subtype of invasive fungal sinusitis and the degree of tissue invasion.     

Synthesis and antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil hydrobromide and its liposomal medicinal form

The antitumor activity of 5-(5′,6′-benzocoumaro-3′-yl)methylaminouracil (BCMU) and its liposomal medicinal form was studied in comparison to 5-fluorouracil (5-FU), a well-known antitumor drug widely used in oncological practice. The half-lethal dose of BCMU is 14.8 ± 4.2 mg/kg, while the optimum effective dose of the drug is 6 mg/kg. In this dose, BCMU combines low toxicity with significant antitumor activity, which is manifested by increased tumor growth inhibition (TGI) at a 19% increase in the lifetime (LT) of experimental animals. The antitumor activity of the liposomal form of BCMU is quantitatively and qualitatively superior to that of the nonmodified compound and 5-FU, which is manifested by the most pronounced TGI value and by a significant LT increase. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 40, No. 6, pp. 6–7, June, 2006.     

Expression of measles virus nucleocapsid protein in osteoclasts induces Paget's disease-like bone lesions in mice.

We targeted the MVNP gene to the OCL lineage in transgenic mice. These mice developed abnormal OCLs and bone lesions similar to those found in Paget's patients. These results show that persistent expression of MVNP in OCLs can induce pagetic-like bone lesions in vivo. INTRODUCTION: Paget's disease (PD) of bone is the second most common bone disease. Both genetic and viral factors have been implicated in its pathogenesis, but their exact roles in vivo are unclear. We previously reported that transfection of normal human osteoclast (OCL) precursors with the measles virus nucleocapsid (MVNP) or measles virus (MV) infection of bone marrow cells from transgenic mice expressing a MV receptor results in formation of pagetic-like OCLs. MATERIALS AND METHODS: Based on these in vitro studies, we determined if the MVNP gene from either an Edmonston-related strain of MV or a MVNP gene sequence derived from a patient with PD (P-MVNP), when targeted to cells in the OCL lineage of transgenic mice with the TRACP promoter (TRACP/MVNP mice), induced changes in bone similar to those found in PD. RESULTS: Bone marrow culture studies and histomorphometric analysis of bones from these mice showed that their OCLs displayed many of the features of pagetic OCLs and that they developed bone lesions that were similar to those in patients with PD. Furthermore, IL-6 seemed to be required for the development of the pagetic phenotype in OCLs from TRACP/MVNP mice. CONCLUSIONS: These results show that persistent expression of the MVNP gene in cells of the OCL lineage can induce pagetic-like bone lesions in vivo.     

Central metabotropic glutamate receptors differentially participate in interleukin-1beta-induced mechanical allodynia in the orofacial area of conscious rats.

The present study investigated the role of central metabotropic glutamate receptors (mGluRs) in interleukin-1beta (IL-1beta)-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Experiments were carried out on male Sprague-Dawley rats weighing 230 to 280 g. After administration of 0.01, 0.1, 1, or 10 pg of IL-1beta into a subcutaneous area of the vibrissa pad, we examined the withdrawal behavioral responses produced by 10 successive trials of an air-puff ramp pressure applied ipsilaterally or contralaterally to the IL-1beta injection site. Subcutaneous injection of IL-1beta produced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Intracisternal administration of CPCCOEt, a mGluR1 antagonist, or MPEP, a mGluR5 antagonist, reduced IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. Intracisternal administration of APDC, a group II mGluR agonist, or L-AP4, a group III mGluR agonist, reduced both IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia. The antiallodynic effect, induced by APDC or L-AP4, was blocked by intracisternal pretreatment with LY341495, a group II mGluR antagonist, or CPPG, a group III mGluR antagonist. These results suggest that groups I, II, and III mGluRs differentially modulated IL-1beta-induced mechanical allodynia, as well as mirror-image mechanical allodynia, in the orofacial area. PERSPECTIVE: Central group I mGluR antagonists and groups II and III mGluR agonists modulate IL-1beta-induced mechanical allodynia and mirror-image mechanical allodynia in the orofacial area. Therefore, the central application of group I mGluR antagonists or groups II and III mGluR agonists might be of therapeutic value in treating pain disorder.     

Ipsilateral Aymand’s and Richter’s hernia, complicated by necrosing fascitis

This study presents the case of a patient with necrobiosis or necrosing fascitis of the inguinal region, secondary to a complicated Amyand’s hernia with a concomitant ipsilateral Richter’s hernia. The patient was treated with open trans-abdominal surgery and hernia repair through the pre-peritoneal approach, plus anti-microbians, and thrice-daily wound cleansing and dressings to the inguinal region. Evolution was satisfactory. There are no reports in the literature of a case such as this.     

Neuronal plasticity in memory and learning abilities: Theoretical position and selective review

Neural plasticity of modality-nonspecific and modality-specific memory and learning abilities pertains to fluid intelligence and crystallized intelligence, respectively. The limbic system with the novelty neurons of the hippocampus interacts with the prefrontal cortex optimization of the orienting reflex and voluntary attention. Brain-derived neurotrophic factor produced by novelty neurons of the hippocampus contributes to long-term memory formation and improves learning abilities in a wide range of disciplines. Synergistic combination of stimulation with “analytical-specific visual perceptual patterns” and “optimally high” physiological activation of the bilateral electrodermal system optimizes the limbic system and prefrontal cortex activity as demonstrated by enhanced prefrontal N450 ERPs to a memory workload paradigm. This is accompanied by improvements in auditory retention tasks, word memorization, higher school achievement and marks, and an amelioration of “analytical-specific perceptual skills” as measured by the Mangina-Test. Intracerebral ERPs to a memory workload paradigm contributed to the elucidation of limbic structures and neocortical sites involved in memory workload processes. The progressive degeneration of these same structures causes the gradual decline of memory functions observed in early Alzheimer's disease. Research findings indicate that ERPs elicited by a memory workload paradigm are sensitive markers for diagnosis, treatment and clinical follow-up of early Alzheimer's patients. In addition, ERPs provide objective measurement of cholinergic medication effects on cerebral functions involved in memory processes through neuropsychophysiological parameters.     

Design of Case-controls Studies with Unscreened Controls

Traditionally in genetic case‐control studies controls have been screened to exclude subjects with a personal history of illness. This control group has the advantage of optimal power to detect loci involved in illness, but requires more work and may incur substantial cost in recruitment. An alternative approach to screening is to use unscreened controls sampled from the general population. Such controls are generally plentiful and inexpensive, but in general there is a risk that some may have the same disease as the cases, which will reduce power to detect associations. We have quantified the extent of this power loss, and produced mathematical formulae for the number of unscreened controls necessary to achieve the same power as a fixed sample of screened controls. The effect of using unscreened controls will also depend on the ratio of the number of screened controls to cases specified in the original study design, and this is also investigated. We have also investigated the cost‐benefits of the screened and unscreened approaches, according to variation in the relative costs of sampling screened and unscreened controls, together with genotyping costs. We have, thus, identified the range of situations in which using unscreened controls is a cost‐effective alternative to the screened control method and could be considered when designing a study. In many of the typical, real‐world situations in complex genetics, the use of unscreened controls is potentially cost‐effective and can, in general, be considered for disorders with population prevalence K_p < 0.2. With the steady reduction in genotyping costs and the availability of common sets of “population controls” this design is likely to become increasingly cost effective.     

A case of drug-induced hematotoxicity: from in vivo to in vitro assessment

As part of the early preclinical development of a new antipsychotic compound, Wistar rats of both sexes were dosed orally for upto 7 days. At high doses, expected changes in appearance and behavior, decreases in bodyweight gain and feed intake but also a fluid and pale bone marrow (BM) were observed. Blood cell counts were normal as were clinical chemical values. BM sections showed a red cell hypoplasia. Circulating reticulocytes and erythroblasts on BM smears were decreased suggesting that the compound might have a selective toxicity for the erythroid lineage. In a mechanistic experiment, rats were dosed for 9 days and phlebotomized after 7 days of exposure to stimulate erythroid regeneration. Red-blood cell mass, reticulocytes and erythropoietin (EPO) levels were monitored before and upto 48 h after bleeding. Results showed that an EPO-mediated pathogenesis could be excluded. The effect of the drug on the formation of Colony-forming units (CFU)-E and CFU-GM was then quantitatively measured in vitro after direct exposure to the compound. In two successive assays, rat or human BM cells were incubated with the drug dissolved in the collection medium at final concentrations of 0.3×10^–7 –3×10^–5 M. In the presence of adequate growth factors, CFU-E and CFU-GM were cultured and cell proliferation was compared between treated and control groups. Our results showed an expected inhibition by the drug of the growth of erythroid progenitors associated to a similar effect on myeloid progenitors. The CFU-E and CFU-GM of both human and rat sources were totally inhibited from the concentration of 3×10^–5 M. The IC₅₀ values were consistent with rat peak plasma levels reached in vivo by the drug. Therefore, the short-term cloning assays performed on rat BM cells were sensitive indicators of the hematotoxicity of the compound and were considered as predictive for human toxicity.