Reduced serotonin synthesis during early embryogeny changes effect of subsequent prenatal stress on persistent pain in the formalin test in adult male and female rats

The considerable evidence supporting a role for serotonin (5-HT) in the embryonic formation of CNS, mediation of prenatal stress, and pain processing is reviewed. Long-term influences of prenatal 5-HT depletion as well as its combination with prenatal stress effects on tonic nociceptive system in 90-day-old Wistar rats were studied in the formalin test. Pregnant dams were injected with para-chlorophenylalanine (pCPA, 400 mg/kg/2 ml, ip), producing 5-HT depletion during the early period of fetal serotonergic system development. The adult offspring from pCPA-treated dams revealed changes in behavioral indices of persistent pain (flexing + shaking and licking) in the formalin test (2.5%, 50 microl) that were accompanied by irreversible morphological alterations in the dorsal raphe nuclei. In the other series of experiments, the role of 5-HT in the mediation of prenatal stress on the behavioral indices of persistent pain was investigated in the adult offspring from dams with 5-HT depletion followed by restraint stress. Stress during the last embryonic week caused much more increase in flexing + shaking and licking in the second tonic phase of the response to formalin in offspring from pCPA- than saline-treated (control) dams. The former was characterized by alterations in the durations of the interphase, the second phase, and the whole behavioral response too. In offspring from pCPA-treated dams, sex dimorphism was revealed in tonic pain evaluated by licking. Together with our previous results in juvenile rats demonstrating the necessity of definite level of prenatal 5-HT for normal development of tonic nociceptive system, the present pioneering findings obtained in adult rats indicate that prenatal 5-HT depletion causes long-term morphological abnormalities in the dorsal raphe nuclei accompanied by alterations in behavioral indices of tonic pain. Early prenatal 5-HT depletion increases vulnerability of tonic nociceptive circuits to the following prenatal stress.     

Brooke-Spiegler syndrome: report of a case with combined lesions containing cylindromatous, spiradenomatous, trichoblastomatous, and sebaceous differentiation

Brooke-Spiegler syndrome is an autosomal dominantly inherited disease with predisposition to cutaneous adnexal neoplasms, most commonly cylindromas and trichoepitheliomas. We report a patient in whom 11 lesions were removed from the scalp and face for various reasons over a period of 3 years. The histopathological survey revealed a plethora of benign adnexal neoplasms showing apocrine, follicular, and sebaceous differentiation occurring independently and conjointly. The histopathological spectrum in our patient included cylindromas, spiradenomas, trichoepitheliomas, small nodular trichoblastomas, and lymphadenomas. Many lesions had hybrid features of two or more neoplasms. By far the most common composite tumor was spiradenocylindroma. Some spiradenocylindromas demonstrated prominent sebaceous or trichoblastomatous differentiation or both. We suggest the terms "sebaceous spiradenocylindroma" and "trichospiradenocylindroma" for these lesions. The occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas is a further proof that spiradenoma and cylindroma are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit.     

Sensorimotor recovery following spaceflight may be due to frequent square-wave saccadic intrusions

Square-wave jerks (SWJs) are small, involuntary saccades that disrupt steady fixation. We report the case of an astronaut (approximately 140 d on orbit) who showed frequent SWJs, especially postflight, but who showed no impairment of vision or decrement of postflight performance. These data support the view that SWJs do not impair vision because they are paired movements, consisting of a small saccade away from the fixation position followed, within 200 ms, by a corrective saccade that brings the eye back on target. Since many returning astronauts show a decrement of dynamic visual function during postflight locomotion, it seems possible that frequent SWJs improved this astronaut's visual function by providing postsaccadic enhancement of visual fixation, which aided postflight performance. Certainly, frequent SWJs did not impair performance in this astronaut, who had no other neurological disorder.     

Pitfalls of the lactating breast on computed tomography

Breasts are usually only incidentally included in computed tomography (CT) scans of the abdomen and chest in spite of the fact that pathologic findings are not rare. Because postpartum women are normally healthy, they rarely require examination; therefore, the presentation of lactating breasts on a CT scan is poorly known. The most common postpartum breast feature is engorgement, which is characterized by painful swelling associated with a sudden increase in milk volume, lymphatic and vascular congestion, and interstitial edema. Its appearance on a CT scan does not seem to have been described in the literature to date. The CT picture of a lactating breast shows the enlarged gland with bilateral cord- and mass-like hyperattenuated tissue. After abrupt cessation of breast-feeding, the edema component supervenes and breast tissue may become hypoattenuated. In such cases, further ultrasound evaluation is needed. We present 3 cases of postpartum breast engorgement as seen on CT.     

Rupture of papillary renal cell carcinoma

OBJECTIVE: Typical signs of papillary renal cell carcinoma (PRCC) are extensive necroses of the tumorous mass, which can modify the clinical appearance of PRCC. These necroses can imitate cysts on radiological examinations (ultrasonography and CT). The tumours are fragile and vulnerable to spontaneous rupture or rupture following minimal trauma (i.e. they act as a locus minoris resistentiae). MATERIAL AND METHODS: A total of 650 patients with a total of 671 renal tumours were surgically treated at our hospital between January 1991 and December 2003. RESULTS: In 16 cases bilateral tumours were found (in all cases RCC) and in five cases two types of tumour were identified in one kidney [all were a combination of conventional RCC (CRCC) and PRCC]. Altogether, 621 tumours (92.5%) were diagnosed as RCCs. Of these, CRCC was found in 563 cases (90.7%), PRCC in 36 (5.8%), chromophobe RCC in 14 (2.3%) and unclassified RCC in 7 (1.1%). All cases of ruptured PRCC were included in our study. Interestingly, only PRCCs ruptured in this series. Rupture was described in three cases of PRCC (8.3%): it was spontaneous in two cases and resulted from a traffic accident in the third. CONCLUSIONS: The extensive necrosis regularly found in PRCC can cause rupture of the tumour followed by retroperitoneal bleeding. Rupture affected <10% of our cases of PRCC. CT findings are usually not characteristic and can mimic a simple haematoma of unknown origin. Similarly, the perioperative finding is unclear in most cases. The final correct diagnosis of the renal tumour is frequently established only by the pathologist.     

Rokitansky and his first description of polyarteritis nodosa

Karl Rokitansky, Professor of Pathology at the University of Vienna described polyarteritis nodosa in 1852 in a 23 year old man with a 5-day history of fever and diarrhoea.     

Enterovirus uveitis

Enterovirus uveitis (EU) is a new infant eye disease that was first observed in 1980. Three distinct subtypes of human echoviruses, EV19/K, EV11/A and EV11/B, caused five hospital outbreaks of EU in different Siberian cities in 1980-1989, affecting approximately 750 children, predominantly below 1 year of age. Sporadic EU cases were also retrospectively diagnosed in other regions of Russia and in different countries of the Former Soviet Union. The illness was characterised by rapid iris destruction and severe complications, including cataract and glaucoma. The disease has been a subject of intensive studies and was reproduced in lower primates after intraocular inoculation of isolated enterovirus strains. Importantly, prototype EV11 and EV19 strains did not induce notable disease in experimental monkeys. Some of the EU-causing strains were shown to be similar phylogenetically and in their pathogenetic properties to the enterovirus strains associated with multisystem hemorrhagic disease of newborns. In this review we present a summary of the vast epidemiological, virological, clinical and experimental data on this new form of ophthalmic infection.     

Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases

Commensal microflora (normal microflora, indigenous microbiota) consists of those micro-organisms, which are present on body surfaces covered by epithelial cells and are exposed to the external environment (gastrointestinal and respiratory tract, vagina, skin, etc.). The number of bacteria colonising mucosal and skin surfaces exceeds the number of cells forming human body. Commensal bacteria co-evolved with their hosts, however, under specific conditions they are able to overcome protective host responses and exert pathologic effects. Resident bacteria form complex ecosystems, whose diversity is enormous. The most abundant microflora is present in the distal parts of the gut; the majority of the intestinal bacteria are Gram-negative anaerobes. More than 50% of intestinal bacteria cannot be cultured by conventional microbiological techniques. Molecular biological methods help in analysing the structural and functional complexity of the microflora and in identifying its components. Resident microflora contains a number of components able to activate innate and adaptive immunity. Unlimited immune activation in response to signals from commensal bacteria could pose the risk of inflammation; immune responses to mucosal microbiota therefore require a precise regulatory control. The mucosal immune system has developed specialised regulatory, anti-inflammatory mechanisms for eliminating or tolerating non-dangerous, food and airborne antigens and commensal micro-organisms (oral, mucosal tolerance). However, at the same time the mucosal immune system must provide local defense mechanisms against environmental threats (e.g. invading pathogens). This important requirement is fulfilled by several mechanisms of mucosal immunity: strongly developed innate defense mechanisms ensuring appropriate function of the mucosal barrier, existence of unique types of lymphocytes and their products, transport of polymeric immunoglobulins through epithelial cells into secretions (sIgA) and migration and homing of cells originating from the mucosal organised tissues in mucosae and exocrine glands. The important role of commensal bacteria in development of optimally functioning mucosal immune system was demonstrated in germ-free animals (using gnotobiological techniques). Involvement of commensal microflora and its components with strong immunoactivating properties (e.g. LPS, peptidoglycans, superantigens, bacterial DNA, Hsp) in etiopathogenetic mechanism of various complex, multifactorial and multigenic diseases, including inflammatory bowel diseases, periodontal disease, rheumatoid arthritis, atherosclerosis, allergy, multiorgan failure, colon cancer has been recently suggested. Animal models of human diseases reared in defined gnotobiotic conditions are helping to elucidate the aetiology of these frequent disorders. An improved understanding of commensal bacteria-host interactions employing germ-free animal models with selective colonisation strategies combined with modern molecular techniques could bring new insights into the mechanisms of mucosal immunity and also into pathogenetic mechanisms of several infectious, inflammatory, autoimmune and neoplastic diseases. Regulation of microflora composition (e.g. by probiotics and prebiotics) offers the possibility to influence the development of mucosal and systemic immunity but it can play a role also in prevention and treatment of some diseases.     

Down-regulation of regulatory subunit type 1A of protein kinase A leads to endocrine and other tumors

Mutations of the human type Ialpha regulatory subunit (RIalpha) of cyclic AMP-dependent protein kinase (PKA; PRKAR1A) lead to altered kinase activity, primary pigmented nodular adrenocortical disease, and tumors of the thyroid and other tissues. To bypass the early embryonic lethality of Prkar1a(-/-) mice, we established transgenic mice carrying an antisense transgene for Prkar1a exon 2 (X2AS) under the control of a tetracycline-responsive promoter. Down-regulation of Prkar1a by up to 70% was achieved in transgenic mouse tissues and embryonic fibroblasts, with concomitant changes in kinase activity and increased cell proliferation, respectively. Mice developed thyroid follicular hyperplasia and adenomas, adrenocortical hyperplasia, and other features reminiscent of primary pigmented nodular adrenocortical disease, histiocytic and epithelial hyperplasias, lymphomas, and other mesenchymal tumors. These were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIbeta protein levels. This mouse provides a novel, useful tool for the investigation of cyclic AMP, RIalpha, and PKA functions and confirms the critical role of Prkar1a in tumorigenesis in endocrine and other tissues.