Prenatal haloperidol treatment decreases nerve growth factor receptor and mRNA in neonate rat forebrain.

Pregnant rats were treated daily with haloperidol (2 mg/kg) for 11 days until 1 day before birth. The levels of nerve growth factor (NGF), its receptor (NGFR) and NGFR-mRNA were measured in forebrain of 2-day old postnatal rats. Using Northern blot analysis, we observed a decrease in NGFR-mRNA. Furthermore, in binding studies, Kd and Bmax of treated rats were lower than in controls, but only in the low affinity binding sites. However NGF and its mRNA did not change after haloperidol treatment. In conclusion, our results suggest that prenatal haloperidol treatment can modify the development of forebrain cells, by changing NGFR expression.     

Evolution of MHC-G in humans and primates based on three new 3'UT polymorphisms

MHC-G is a class Ib (non-classical) major histocompatibility complex (MHC) whose functional and evolutionary characteristics are still under scrutiny. The study of noncoding sequences in the MHC genes may provide important phylogenetic information. In this work we have sequenced the MHC-G exon 8, which encodes for the 3'UT region, in different species of primates. It has been shown that: (1) a previously described 14 base pair (bp) deletion polymorphism is human-specific and the HLA-G alleles may be classified according to its absence or presence; (2) another newly described 3 bp deletion/insertion polymorphism is also human-specific; and (3) another newly described 51 bp deletion polymorphism is common to Pongidae and humans, but is not found in other primates belonging to the Cercopithecinae family. A hypothesis on the evolutionary pathway of this gene is put forward in the light of these findings.     

Shashi XLMR syndrome: report of a second family

This report describes a family with mental retardation in two brothers. The pedigree is consistent with either X-linked mental retardation or autosomal recessive inheritance. The clinical features consist of coarse face, prominent lower lip, large testes, and obesity. This same constellation of findings was observed in a family with X-linked mental retardation (XLMR) reported by Shashi et al. [2000: Am J Hum Genet 66:469-479]. Furthermore, haplotype analysis was consistent with localization of the Shashi XLMR syndrome in Xq26-q27. Thus, the family likely represents a second occurrence of the Shashi XLMR syndrome.     

Limb preference after unilateral pyramidotomy in adult and neonatal rats

As previously reported, unilateral pyramidotomy in newborn rats results in the development of an aberrant ipsilateral corticospinal tract that originates from the intact side. In the present study, limb preference after unilateral pyramidotomy in adult and neonatal rats was examined in search of differences that might correlate with this aberrant tract. However, no significant differences were observed between the two groups. Postoperatively, adult animals preferred the limb corresponding to the intact corticospinal tract in spite of a pre- and postoperative testing bias toward the opposite limb. Similarly, the animals that sustained neonatal lesion followed by testing at maturity also preferred the limb corresponding to the normal crossed corticospinal tract.     

Social–Emotional Profiles of PTSD,Complex PTSD,and Borderline Personality Disorder Among Racially and Ethnically Diverse Young Adults: A Latent Class Analysis

The debate around the construct validity of complex posttraumatic stress disorder (CPTSD) has begun to examine whether CPTSD diverges from posttraumatic stress disorder (PTSD) when it co‐occurs with the diagnosis of borderline personality disorder (BPD). The present study (a) examined the construct validity of CPTSD through a latent class analysis of a non–treatment‐seeking sample of young trauma‐exposed adults and (b) characterized each class in terms of trauma characteristics, social emotions (e.g., shame, guilt, blame), and interpersonal functioning. A total of 23 dichotomized survey items were chosen to represent the symptoms of PTSD, CPTSD, and BPD and administered to 197 trauma‐exposed participants. Fit statistics compared models with 2–4 latent classes. The four‐class model showed the best fit statistics and clinical interpretability. Classes included a “high PTSD+CPTSD+BPD” class, characterized by high‐level endorsement of all symptoms for the three diagnoses; a “moderate PTSD+CPTSD+BPD” class, characterized by endorsement of some symptoms across all three diagnoses; a “PTSD” class, characterized by endorsement of the ICD‐11 PTSD criteria; and a “healthy” class, characterized by low symptom endorsement overall. Pairwise comparisons showed individuals in the high PTSD+CPTSD+BPD class to have the highest levels of psychological distress, traumatic event history, adverse childhood experiences, and PTSD symptoms. Shame was the only social emotion to significantly differ between the classes, p = .002, η² = .16. The findings diverge from the literature, indicating an overlap of PTSD, CPTSD, and BPD symptoms in a non–treatment‐seeking community sample. Further, shame may be a central emotion that differentiates between presentation severities following trauma exposure.     

Pentylenetetrazole induced changes in zebrafish behavior, neural activity and c-fos expression

Rodent seizure models have significantly contributed to our basic understanding of epilepsy. However, medically intractable forms of epilepsy persist and the fundamental mechanisms underlying this disease remain unclear. Here we show that seizures can be elicited in a simple vertebrate system e.g. zebrafish larvae (Danio rerio). Exposure to a common convulsant agent (pentylenetetrazole, PTZ) induced a stereotyped and concentration-dependent sequence of behavioral changes culminating in clonus-like convulsions. Extracellular recordings from fish optic tectum revealed ictal and interictal-like electrographic discharges after application of PTZ, which could be blocked by tetrodotoxin or glutamate receptor antagonists. Epileptiform discharges were suppressed by commonly used antiepileptic drugs, valproate and diazepam, in a concentration-dependent manner. Up-regulation of c-fos expression was also observed in CNS structures of zebrafish exposed to PTZ. Taken together, these results demonstrate that chemically-induced seizures in zebrafish exhibit behavioral, electrographic, and molecular changes that would be expected from a rodent seizure model. Therefore, zebrafish larvae represent a powerful new system to study the underlying basis of seizure generation, epilepsy and epileptogenesis.     

Minimally invasive palliative tumor therapy guided by imaging techniques: the UCLA experience

Imaging-guided palliative therapy of recurrent and/or inaccessible head and neck tumors may soon become clinically practical since sensitive and noninvasive monitoring techniques of energy deposition in tissues are now available. Interstitial tumor therapy (ITT) is a technique whereby a source of energy (laser, radiofrequency, ultrasonic, cryoenergy, etc.) is directly applied into tumors at various depths. Recent studies have demonstrated the efficiency of ultrasound (UTZ) and magnetic resonance imaging (MRI) for real and/or "near" real time tumor and vessel identification as well as monitoring and quantifying energy-induced tissue damage. We now report our initial clinical experience with patients in which UTZ and/or MRI-guided ITT techniques were successfully applied for the treatment of recurrent, nonresectable, local, and/or metastatic head and neck carcinomas. Patients were treated on an outpatient basis either in the operating room or in an upgraded specially equipped SIGNA 1.5T MR suite. Most patients tolerated these procedures well and were successfully palliated for periods ranging from 3 months to 5 years posttreatment. The upgrades introduced in a standard MRI suite, the clinical experience, and future perspectives will be reviewed.     

Acute attacks in the extremities of persons living in an area endemic for bancroftian filariasis: differentiation of two syndromes

The natural history of lymphatic disease in human filariasis remains unclear, but recurrent episodes of acute lymphangitis are believed to constitute a major risk factor for the development of chronic lymphoedema and elephantiasis. Prospective analysis of 600 patients referred to the filariasis clinic of the Centro de Pesquisas Aggeu Magalh?es/FIOCRUZ in Recife, Brazil, indicated that 2 distinct acute syndromes accompanied by lymphangitis occur in residents of this filariasis-endemic area. One syndrome, which we call acute filarial lymphangitis (AFL), is caused by the death of adult worms. It is relatively uncommon in untreated persons, usually is asymptomatic or has a mild clinical course, and rarely causes residual lymphoedema. The second syndrome, of acute dermatolymphangioadenitis (ADLA), is not caused by filarial worms per se, but probably results from secondary bacterial infections. ADLA is a common cause of chronic lymphoedema and elephantiasis in Recife as well as in other areas of Brazil where lymphatic filariasis is not present. The syndromes of AFL and ADLA can be readily distinguished from each other by simple clinical criteria.     

Association of HLA-DR11 with the anaphylactoid reaction caused by nonsteroidal anti-inflammatory drugs

BACKGROUND: Several HLA alleles have been associated with asthma induced by nonsteroidal anti-inflammatory drugs (NSAIDs). The existence of HLA markers linked to other NSAID-induced reactions, such as cutaneous and anaphylactoid reactions, has not been established. OBJECTIVE: The purpose of our work was to study the HLA-DRB1 and HLA-DQB1 alleles in patients with cutaneous and anaphylactoid reactions caused by NSAIDs. METHODS: We have analyzed 114 HLA DRB1 and 26 HLA-DQB1 alleles in 21 patients with anaphylactoid reactions caused by NSAIDs, 47 patients who had exclusively cutaneous reactions during single-blind, placebo-controlled oral challenges with NSAIDs, and 167 tolerant control subjects (29 of whom had also had an IgE-mediated anaphylaxis to different agents). HLA-DRB1 and HLA-DQB1 alleles were typed by the polymerase chain reaction sequence-specific primers method with genomic DNA. RESULTS: The frequency of HLA-DR11 alleles was 58.8% in the anaphylactoid reaction group, compared with 15.9% in the NSAID-tolerant healthy control subjects (OR, 7:3; 95% confidence interval, 2.8-19.0; P <.02) and 6.3% in the group of the patients with a tolerance for NSAIDs and with IgE-mediated anaphylaxis (OR, 18.75; 95% confidence interval, 4.3-81.1; P <.004). No differences were observed among HLA-DR11 alleles analyzed. There were no significant HLA-DQB1 associations with NSAID-induced anaphylactoid reactions. Patients with cutaneous reactions had HLA frequencies that did not differ significantly from the tolerant control subjects. CONCLUSION: The HLA-DRB1*11 alleles showed a positive association with NSAID-induced anaphylactoid reactions.