Neonatal 6-hydroxydopa, but not DSP-4, elevates brainstem monoamines and impairs inhibitory avoidance learning in developing rats

The involvement of brain monoamines in learning and memory in developing rats was studied by comparing the effects of 3 different noradrenergic neurotoxin treatments. Two experimental groups of male Sprague-Dawley rat pups were injected systemically with 50 micrograms/g of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) either on the day of birth or on postnatal days 17-18. Rats in the third experimental group were injected systemically with 60 micrograms/g of 6-hydroxydopa (6-OHDOPA) on postnatal days 0 and 2. Control littermates received vehicle. The animals were trained on an inhibitory avoidance task on postnatal days 27-29 and tested for retention 24 h later. The drug treatments produced comparable depletion of norepinephrine in the hippocampus and frontal cortex. 6-OHDOPA, but neither DSP-4 treatment, significantly elevated brainstem concentrations of norepinephrine and serotonin. In addition, 6-OHDOPA, but not DSP-4, significantly impaired retention of the inhibitory avoidance task. The impairment did not reflect insensitivity to the footshock used in training: both neonatal drug treatments tended to lower, not raise, footshock thresholds, as measured by a flinch test. High affinity choline uptake was not affected by either neonatal drug treatment in any of the brain areas examined. Thus, the 6-OHDOPA-induced behavioral deficit did not involve altered acetylcholine function. The results implicate brainstem monoamines in the modulation of learning and memory during development.     

Recent trends in early outcome of adult patients after heart transplantation: a single-institution review of 251 transplants using standard donor organs.

Older age, prior transplantation, pulmonary hypertension, and mechanical support are commonly seen in current potential cardiac transplant recipients. Transplants in 436 consecutive adult patients from 1994 to 1999 were reviewed. There were 251 using standard donors in 243 patients (age range 18-69 years). To emphasize recipient risk, 185 patients who received a nonstandard donor were excluded from analysis. The indications for transplant were ischemic heart disease (n = 123, 47%), dilated cardiomyopathy (n = 82, 32%), and others (n=56, 21%). One hundred and forty-nine (57%) recipients were listed as status I; 5 and 6% were supported with an intra-aortic balloon and an assist device, respectively. The 30-d survival and survival to discharge were 94.7 and 92.7%, respectively; 1-year survival was 89.1%. Causes of early death were graft failure (n = 6), infection (n = 4), stroke (n = 4), multiorgan failure (n = 3) and rejection (n = 2). Predictors were balloon pump use alone (OR= 11.4, p =0.002), pulmonary vascular resistance > 4 Wood units (OR = 5.7, p = 0.007), pretransplant creatinine > 2.0 mg/dL (OR = 6.9, p = 0.004) and female donor (OR = 8.3, p = 0.002). Recipient age and previous surgery did not affect short-term survival. Heart transplantation in the current era consistently offers excellent early and 1-year survival for well-selected recipients receiving standard donors. Early mortality tends to reflect graft failure while hospital mortality may be more indicative of recipient selection.     

Early experience with minimally invasive esophagectomy in head and neck surgical patients

BACKGROUND: Minimally invasive esophagectomy (MIE) via thoracoscopy and laparoscopy have reduced the morbidity and mortality of total esophagectomy at experienced centers. MIE has not been evaluated in combination with major head and neck surgery, or in the otolaryngology literature. METHODS: Case series of 11 consecutive patients undergoing either open or MIE with an ablative neck procedure. RESULTS: Comparing 4 MIEs and 7 open operations, similar operative time, blood loss, and ICU and hospital length of stay were observed. There was one mortality in the open group. A 100% rate of major complications was observed in the MIE group. CONCLUSION: Our multidisciplinary team was unable to achieve improved outcomes in a series of head and neck surgical patients undergoing MIE. This result may represent an early stage of the learning curve for MIE, but may also be attributed to the escalated surgical requirements of head and neck patients.     

Biocompatibility of Hemoglobin Solutions. I. Reactions of Vascular Endothelial Cells to Pure and Impure Hemoglobins

Hemoglobin (Hb) solutions can cause vasoconstriction and activation of intravascular coagulation. Because the endothelium plays a major role in the regulation of vascular tone and hemostasis, a study was conducted of human umbilical vein endothelial cells (EC) incubated with various Hbs. Cell injury was evaluated by electron microscopy and the release of lactic dehydrogenase, H2O2, and procoagulant "tissue factor." Cell reaction was assessed by the measurement of 6-keto-prostaglandin F (PGF)1 alpha (metabolite of prostacyclin) and thromboxane B2 (metabolite of thromboxane A2). Incubation with unmodified bovine hemoglobin for 24 h caused no cell injury and a reaction characterized by 48.4 +/- 8.2% increase in 6-keto-PGF1 alpha production, accompanied by 40.2 +/- 9.4% reduction in thromboxane (Tx)B2 (compared with a control group of EC incubated with saline solution). Incubation with a nonpure Hb solution (Hb plus red blood cell membrane aminophospholipids; a-PLs) caused cell injury with significant release of tissue factor, plus a reaction characterized by 97.5 +/- 12.5% increase in TxB2 production accompanied by 25.3 +/- 3% reduction in 6-keto-PGF1 alpha. A second nonpure Hb [Hb plus bacterial environmental endotoxin (E)] caused cell injury, the release of tissue factor, and increased production of both prostaglandins, with greater release of TxB2 (197 +/- 17%) than of 6-keto-PGF1 alpha (112 +/- 8.3%). These data indicate that the endothelium reacts differently to pure and nonpure hemoglobins. The biocompatibility of Hb solutions, with regard to vasoconstriction and activation of intravascular coagulation, depends on the absence of stromal a-PLs and bacterial E.     

High prevalence of hepatitis B virus pre-s mutant in countries where it is endemic and its relationship with genotype and chronicity

It has been reported that hepatitis B virus (HBV) mutants carrying mutations in the pre-S region can be found in infected patients. In this study, we investigated the prevalence of the HBV variant with the pre-S mutant in different geographic regions, including countries with low and high levels of endemic HBV infection, and analyzed the correlation with clinical findings. We examined 387 HBV DNA-positive serum samples from individuals among 12 countries, consisting of Vietnam, Myanmar, Thailand, China, Korea, Nepal, Japan, Russia, Spain, United States, Bolivia, and Ghana. HBV pre-S mutants were detected in 71 (18.3%) of 387 serum samples tested. This mutant was the most prevalent in Vietnam (36%), followed by Nepal (27.3%), Myanmar (23.3%), China (22.4%), Korea (14.3%), Thailand (10.5%), Japan (7.7%), and Ghana (4.3%). In contrast, no case with this mutation was found in Russia, Spain, United States, and Bolivia. Among the HBV deletion mutations, 15.5% (11 of 71) occurred in the pre-S1 and 46.5% (33 of 71) in the pre-S2 regions. Eight (11.3%) cases had a mutation in both the pre-S1 and pre-S2 regions. In addition, a point mutation at the pre-S2 starting codon was observed in 19 (26.7%) cases. The detection rate of the HBV mutant in patients with hepatocellular carcinoma was significantly higher than in other patients (P < 0.05). Furthermore, these mutants were found more frequently in genotype B (25%) and genotype C (24.5%) than in the other genotypes (P < 0.05). Our results indicated that there was a high prevalence of HBV pre-S mutation in regions of endemic HBV infection in Asia. Furthermore, the pre-S mutation appeared to be correlated with hepatocellular carcinoma and HBV genotypes.     

Complete Sequence of a 93.4-kb Contig from Chromosome 3 of Trypanosoma cruzi Containing a Strand-Switch Region

We have initiated large-scale sequencing of the third smallest chromosome of the CL Brener strain of Trypanosoma cruzi and we report here the complete sequence of a contig consisting of three cosmids. This contig covers 93.4 kb and has been found to contain 20–30 novel genes and several repeat elements, including a novel chromosome 3-specific 400-bp repeat sequence. The intergenic sequences were found to be rich in di- and trinucleotide repeats of varying lengths and also contained several known T. cruzi repeat elements. The sequence contains 29 open reading frames (ORFs) longer than 700 bp, the longest being 5157 bp, and a large number of shorter ORFs. Of the long ORFs, seven show homology to known genes in parasites and other organisms, whereas four ORFs were confirmed by sequencing of cDNA clones. Two shorter ORFs were confirmed by a database homology and a cDNA clone, respectively, and one RNA gene was identified. The identified genes include two copies of the gene for alanine-aminotransferase as well as genes for glucose-6-phosphate isomerase, protein kinases and phosphatases, and an ATP synthase subunit. An interesting feature of the sequence was that the genes appear to be organized in two long clusters containing multiple genes on the same strand. The two clusters are transcribed in opposite directions and they are separated by an ~20-kb long, relatively GC-rich sequence, that contains two large repetitive elements as well as a pseudogene for cruzipain and a gene for U2snRNA. It is likely that this strand switch region contains one or more regulatory and promoter regions. The reported sequence provides the first insight into the genome organization of T. cruzi and shows the potential of this approach for rapid identification of novel genes.     

LARP7 variants and further delineation of the Alazami syndrome phenotypic spectrum among primordial dwarfisms: 2 sisters

Alazami syndrome (AS) (MIM# 615071) is an autosomal recessive microcephalic primordial dwarfism (PD) with recognizable facial features and severe intellectual disability due to depletion or loss of function variants in LARP7. To date, 15 patients with AS have been reported. Here we describe two consanguineous Algerian sisters with Alazami PD due to LARP7 homozygous pathogenic variants detected by whole exome sequencing. By comparing these two additional cases with those previously reported, we strengthen the key features of AS: severe growth restriction, severe intellectual disability and some distinguishing facial features such as broad nose, malar hypoplasia, wide mouth, full lips and abnormally set teeth. We also report significant new findings enabling further delineation of this syndrome: disproportionately mild microcephaly, stereotypic hand wringing and severe anxiety, thickened skin over the hands and feet, and skeletal, eye and heart malformations. From previous reviews, we summarize the main etiologies of PD according to the involved mechanisms and cellular pathways, highlighting their clinical core features.