Significance of immunohematologic testing in mother and newborn ABO incompatibility.

The aim of this study was to define risk factors for jaundice and anemia in newborns with a positive direct antiglobulin test (DAT) and/or with an incompatible crossmatch due to ABO incompatibility between mother and newborn. ABO incompatibility has become a more significant cause of hemolytic disease of the fetus and newborn since the introduction of effective anti-D prophylaxis. The condition is common and, if clinically significant at all, causes only mild jaundice, which can be treated with phototherapy (PT). However, rare and serious presentations, requiring transfusion therapy, have been noted. Clinical, laboratory, and immunohematologic data were collected retrospectively from medical records of ABO-incompatible newborns and their mothers over a 5-year period (2016-2020) from University Hospital Centre Zagreb. Two groups of newborns were compared: those who needed medical intervention because of hyperbilirubinemia or anemia and those who did not. Within the group of newborns requiring intervention, we also compared those with A and B blood groups. Over the 5-year period, 72 of 184 (39%) newborns required treatment. The treatment was PT in 71 (38%) newborns and erythrocyte transfusion in 2 (1%). In 112 (61%) newborns, ABO incompatibility was an accidental finding while performing blood group typing; these newborns did not require any therapy. In conclusion, we found a statistical, but not clinically significant, difference between the groups of treated and untreated newborns, related to the mode of delivery and DAT positivity within hours of delivery. There were no statistically significant differences in characteristics between the groups of treated newborns, except for two newborns with blood group A who received erythrocyte transfusions.

The anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents.

1. In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra) may involve modulation of inhibitory neurotransmission. 2. GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3. LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4. These minor direct effects contrasted with a potent ability of LEV (EC(50)=1 - 10 microM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5. Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6. LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7. The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV.

Pregabalin (Pfizer).

Pfizer is developing pregabalin, a follow-up compound to its GABA agonist gabapentin, for the potential treatment of several central nervous system (CNS) disorders including epilepsy, neuropathic pain, anxiety and social phobia [286425]. By December 2000, Pfizer anticipated filing an NDA for pregabalin for seven major indications (beginning with neuropathic pain and add-on epilepsy), with the FDA by the end of 2001. Filings for generalized anxiety disorder (GAD), social anxiety disorder and fibromyalgia are expected to take place in 2002, and filings for epilepsy monotherapy and panic disorders are expected to take place in early- and late-2003, respectively [336918], [393182], [399956]. By January 2001, pregabalin was in phase II development in Japan for the potential treatment of neuropathic pain, with an anticipated approval date of 2005 [394827]. However, following analysis by the FDA of a mouse study that showed incidence of a specific tumor type, Pfizer announced in February 2001, that it is restricting the use of pregablin in some clinical patients [398726] and it has frozen trials for neuropathic pain [398785]. In April 2001, Morgan Stanley Dean Witter predicted potential sales of $350 million in 2002, rising to $1750 million in 2006, with peak sales in excess of $2000 million [406923].

Demonstration of perycriptal fibroblasts in inflammatory-regenerative and dysplastic epithelial lesions of the flat colonic mucosa.

The aim of the paper is the definition of perycriptal fibroblasts (PCFs) distribution in inflammatory-regenerative and dysplastic epithelial lesions of flat bowel mucosa. The relationship between the presentation of PCFs and the grade of inflammatory-regenerative and dysplastic process in the flat colon mucosa is also examined. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions (108 mild, 58 moderate, and 30 severe dysplasia). The demonstration of PCFs in biopsy specimens was performed by immunohistochemistry using monoclonal antibody for alpha smooth muscle actin, muscle-specific actin (HHF-35), vimentin and desmin, in comparison with normal mucosa and adenocarcinoma. The PCFs were reduced in inflammatory-regenerative and dysplastic mucosa. The reduction was significantly related with the grade of epithelial dysplasia. The carcinomas tended to lack PCF network. During inflammatory-regenerative and dysplastic process in flat bowel mucosa, PCFs express alpha smooth muscle actin, muscle specific actin, vimentin and desmin, showing the phenotypical growing expression of potentially present smooth muscle differentation features of fibroblasts. These findings suggest that the reduction of PCFs in dysplastic epithelial lesions may relate to the development of dysplasia in flat bowel mucosa. Reduced number of PCFs in dysplastic mucosa may be a marker for the risk of preneoplastic and neoplastic progression in bowel mucosa.

Carcinoembryonic antigen (CEA) in colonic inflammatory-regenerative and dysplastic epithelial lesions.

AIM: Immunohistochemical study of carcinoembryonic antigen (CEA) distribution in inflammatory-regenerative and dysplastic changes of bowel mucosa. The relationship between the presentation of CEA and the intensity of inflammatory-regenerative and dysplastic processes in the flat colon mucosa was also examined. METHODS: Biopsy specimens from 105 patients were examined: 45 classified as inflammatory-regenerative and 60 as dysplastic (21 mild, 23 moderate, and 16 severe dysplasia). The expression of CEA was assessed on the basis of location, quantity, and intensity of CEA immunostaining, by counting antigen-positive cells, and the presence of antigen in the lumen of crypts and glycocalyx on the surface of the mucosa. Using a semiquantitative method, antigen staining intensity was defined as weak, moderate, and intense. RESULTS: The quantity of CEA in columnar, goblet mucous, and undifferentiated cells, as well as in the glycocalyx on the surface of the mucosa and in the crypts' content increased proportionally with the intensity of epithelial dysplasia. In inflammatory-regenerative lesions, CEA was located in the apical and supranuclear part of the cytoplasm, and in the dysplastic mucosa, in lateral and basal parts of the cells. CONCLUSION: The quantity of immunohistochemically demonstrable CEA and its intracellular distribution changed in the colon mucosa during the transition from regenerative to dysplastic epithelial lesions. The intensity of CEA expression was closely related to the intensity of dysplastic lesion.

[Multiple neoplasms]. / Multiple neoplazme.

This paper describes observation on multiple carcinomas, with emphasis on double carcinomas of the lungs and other organs. The paper presents four cases of multiple neoplasmas and goes on to discuss eventual etiopathogenesis of multiple malignancies. Of the four cases presented in this paper, three cover double carcinoma of the throat and lungs, and in the fourth, double carcinoma of the lung and bladder. Three of the cases covered relate to metachronous carcinoma and the fourth case to synchronous carcinoma.

[Diagnostic and prognostic contribution of somatosensory evoked potentials by truncular and dermatomal stimulation in lumbosacral radiculopathy. Apropos of 120 cases surgically-treated]. / L'apport diagnostique et pronostique des potentiels évoqués somesthésiques par stimulation tronculaire et dermatomale dans les conflits disco-radiculaires lombaires. A propos de 120 cas opérés.

Lower-limb somatosensory evoked potentials (SEPs) of nerve-trunk (peroneal nerve, posterior tibial nerve) and dermatomal (L5 and S1) stimulation were recorded in 120 patients suffering from lumbosacral disk disease. Recordings were performed before surgery and on Days 4 and 50 after surgery. Electromyography was also performed before surgery. Dermatomal SEPs were shown to be sensitive (70%) and specific in both terms of their lateralizing value and their ability to identify the L5 or S1 level. Moreover, combining SEPs and EMG significantly increased the sensitivity of the electrophysiological testing when compared with each method alone. There was no relationship between SEPs performed before surgery and surgical outcome. Inversely, we demonstrated the prognostic value of SEPs performed on Day 4, SEP normalization at Day 4 was associated with a good outcome at Day 50 in 91.8% of examined cases, while the persistence of pathological SEPs at Day 4 was associated with poor outcome at Day 50 in 56% of the cases.

[Acute hemorrhagic ulcer in a 3-month-old child]. / Akutni krvareci ulkus kod tromjesecnog djeteta.

A case of the acute haemorrhaging ulcus in a three-months old infant with lethal outcome is presented in this paper. The unclear proximal gastrointestinal haemorrhage didn't indicate the possibility of the presence of ulcer, due to the absence of frequent etiologic factors of the inception at this age.

[Morphologic changes in the pulp and surrounding structures of the teeth in irradiated animals]. / Morfoloske promjene pulpe i okolnih struktura zuba kod ozracenih zivotinja.

Several animals of the same breed (11 swine-white Landrace) were used in the research. Irradiation was made by radiation from the linear accelerator with lethal doses (3,68-4, 48 Gy). The changes on incisors and molars in the perished animals were observed as well as the changes on the surrounding structures of teeth. In the examined histological incisions of the dental pulp, paradontium, alveolar part of the bone and gingival part of the mucose of the oral cavity in the animals were found extensive confluent bleeding, dilatation of blood vessels with expressive edema of blood vessels intima. The endothelium showed the signs of edema, prominence toward the lumen or desquamation in the lumen. There were shallow defects in the gingival mucosa due to the necrosis and desquamation top-cover epithelium. The described changes fit into the findings of a large number of researches who accent hemorrhagic diathesis with petechial ecchymotic and confluent bleedings in many organs and tissues.

[Dental pulp in carious teeth]. / Zubna pulpa kariozno oboljelih zuba.

Various etiologic causes lead to dental pulp changes ranging from inflammation to necrosis. The most frequent changes, however, are caused by bacterial activity and toxins from carious process. According to the opinion of various authors and on the basis of our investigations the conclusion can be made that all the forms of dental pulp changes can be developed as the sequela of the disease of supporting apparatus. Pathohistologic examination of dental pulp of cariously damaged teeth showed that the occurred changes are mostly the sequela of inflammation and regressive and progressive changes are found as well.

[Malignant melanoma arising from a cystic dermoid teratoma of the ovary]. / Maligni melanom porijeklom iz cisticnog dermoidnog teratoma ovarija.

The primary malignant melanoma of the ovary is a rare kind of neoplasm. This one is in the world literature the eleventh well-documented case having developed in the ovary of a 66-year-old woman. A unilateral ovarian teratoma was removed, within which a malignant melanoma was found. The junctional activity of melanocytes was demonstrated in the epidermis within the teratoma. An extraovarian primary melanoma was not observed. The patient was treated with a bilateral adnexectomy and hysterectomy.

[Neurological involvement as manifestation of Behçet's disease. 4 clinical case reports]. / Atteintes neurologiques révélatrices d'une maladie de Behçet. Quatre observations cliniques.

We report four patients with Behçet's disease characterized by initial and predominant neurological signs and symptoms. In three cases, a clinical picture of relapsing meningoencephalitis preceded the appearance of the classical signs of the disease for several months or years; in the fourth case, an acute febrile aseptic meningitis coincided with the development of bipolar aphthosis and uveitis. Disease activity was linked to a blood inflammatory syndrome and neutrophilic leucocytosis. Acute phases were associated with CSF mixed pleocytosis and high protein content. Brain CT scans and MRI were very effective to detect lesions which are mainly located in the brain stem and basal ganglia. High-dose corticosteroids and, in cases of relapses, immunosuppressive drugs were required to treat these severe forms of Behçet's disease.

[Isolation of viruses from autopsy material during the Coxsackie virus epidemic in Sarajevo in 1985]. / Izolacija virusa iz obdukcionog materijala za vrijeme epidemije coxsackie viroza, u Sarajevu 1985. god.

In this paper were presented results of isolation of vira from some organs of the dead newborn infants during the epidemy Coxsackie B virosis in Sarajevo in 1985. 12 newborn died. Obduction was done in seven newborn. From the seven obducated, in six were isolated Coxsackie B-3 vira from heart, lungs, brain, liquor, blood, heart blood but the attempts of isolation of the vira from intestine and from pericardial liquor did not succeed.

Plasminogen activators in developing peripheral nervous system, cellular origin and mitogenic effect.

Newborn rat dorsal root ganglia release two different plasminogen activators (PAs): the urokinase (UK) and the tissue (tPA) type. The former is secreted by neurons while the latter is secreted by Schwann cells. tPA release by Schwann cells is modulated by choleratoxin, a known mitogen for these cells. UK but not tPA stimulates in a dose-dependent fashion the proliferation of Schwann cells. This effect is observed in the absence of plasminogen, suggesting that the substrate for PAs in the developing nervous system is not plasminogen. Since UK is secreted by neurons, our data suggest a new mechanism for neuronal control of Schwann cell proliferation.

Potassium-induced release of neuronotoxic activity by astrocytes.

Medium conditioned by newborn rat cerebral cortex microexplants contains neuronotoxic activity for cerebellar granule cells and hippocampal neurons. The neuronotoxic activity is associated with low-molecular weight molecule(s) (less than 1000 Da) and resists to heating and to freezing and thawing. Using nearly homogenous cultures of neurons or astrocytes, we show that the neuronotoxic activity is released by the latter cell type. This release is enhanced by increasing extracellular K+-concentration. Astrocytes also secrete neuronotrophic activity whose release is not affected by external K+. Neurons can be desensitized against the neuronotoxic activity.

Central nervous system-directed neuronotrophic activity present in red blood cells.

A new neuronotrophic factor has been identified in extracts of vertebrate red blood cells. The factor supports the survival in culture of neurons from vertebrate central nervous systems, and does not support the survival of several peripheral ganglionic neurons. The active molecule appears to be a slightly acidic protein of 30,000-100,000 daltons.

Plasminogen activator is a mitogen for astrocytes in developing cerebellum.

Newborn rat cerebellum microexplants cultured in Minimal Essential Medium with glucose and insulin released plasminogen activator (PA), which was detected in living cultures by a substrate overlay assay. Gel electrophoresis of cerebellum-conditioned medium followed by zymography resolved PA activity in two separate bands of 48,000 and 75,000 daltons apparent mol. wt. Using specific antisera, these bands were shown to be respectively urokinase and tissue-type PA. Cerebellum conditioned medium as well as purified human urokinase induced the proliferation and outgrowth of glial fibrillary acid protein-positive cells from newborn cerebellar microexplants. The effect was suppressed by the serine protease inhibitor phenyl methanesulfonylfluoride. Since PAs are most likely of neuronal origin, we suggest that at least one of these proteases acts as a neuronoglial mitogenic signal during development.

Laminin promotes cerebellar granule cells migration in vitro and is synthesized by cultured astrocytes.

Newborn rat cerebellum microexplants have been used as a model to study neuronal migration. Laminin in a substrate-bound form modifies extensively the migratory behavior of the neurones, an effect which is blocked if antilaminin antibodies are present during the assay. 35S methionine incorporation followed by SDS-PAGE electrophoresis, fluorography and immunoprecipitation with antilaminin antibodies allowed to demonstrate that laminin is synthesized and secreted by cultured newborn rat cerebellum as well as by cultured newborn rat cerebral cortex astrocytes.

Pyruvate participation in the low molecular weight trophic activity for central nervous system neurons in glia-conditioned media.

Conditioned media from glial cell cultures contain low molecular weight agents which can support survival of CNS neurons in the absence of recognized protein neuronotrophic factors. A similar support is provided to CNS neurons by selected basal media, and pyruvate is the critical medium constituent responsible for their trophic competence. Eagle's basal medium, which contains no pyruvate, acquires pyruvate when conditioned over astroglial cell cultures. Enzymatic degradation of the pyruvate in the astroglia-conditioned medium leads to corresponding losses in its low molecular weight trophic activity for CNS neurons. Quantitative correlations between pyruvate content and CNS trophic activity demonstrate that pyruvate is the main trophic ingredient of the glia-conditioned medium, and other low molecular weight substances, acquired during conditioning, reduce the pyruvate concentration required for its trophic effect. The "pyruvate-sparing" substances, as yet unidentified, are not the serine and Fe3+ which have pyruvate-sparing competence for peripheral, ciliary ganglionic neurons. These findings, together with previous observations, propose that prenatal neurons fail to generate or retain endogenous pyruvate at the levels for their survival-sustaining activities.