Effects of nicotine on bacterial toxins associated with cot death

Toxins produced by staphylococci and enterobacteria isolated from the nasopharynx of cases of sudden infant death syndrome (SIDS) have a lethal effect when injected into chick embryos. If the toxins are progressively diluted the lethal effect disappears, but certain combinations of toxins show synergy so that if sublethal doses are mixed a highly lethal effect is produced. In this paper it is shown that nicotine at very low concentrations (less than that produced in man by 0.05 cigarettes) potentiates the lethal action of certain SIDS associated bacterial toxins and markedly potentiates the lethal action of synergistic combinations of bacterial toxins. These results could explain, at least in part, why parental smoking increases the risk of SIDS. They also provide further support for the common bacterial toxin hypothesis of cot death.     

Iron homeostasis in beta-thalassemic mice

To explore the pathogenesis of nontransfusional iron overload in iron- loading anemia, we examined features of external iron exchange, internal iron kinetics, and tissue iron burden in adult mice with inherited gene-deletion beta-thalassemia. Mice homozygous for beta- thalassemia display moderate anemia, reticulocytosis, and shortened red cell survival, whereas heterozygous carriers appear hematologically normal. Quantitative iron determination revealed that iron content and concentration in liver, spleen, and kidney, but not heart, were far higher (P less than .01) in 15-to 35-week old homozygous thalassemic mice than in age-matched normal and heterozygous controls; of these tissues, iron content increased with age only in kidneys (P = .01) of homozygous affected mice. Although plasma iron levels were only minimally elevated in homozygotes, plasma iron turnover was threefold greater (P less than .001) than that seen in heterozygote controls. Nevertheless hyperabsorption of enteric radioiron, discernible among homozygous thalassemic mice as late as 6 to 8 weeks after birth, was not observed in older mice, additionally, thalassemic and control mice at 18 to 34 weeks showed comparable iron excretion after intravenous radioiron. We conclude that adult mice with beta-thalassemia regain balanced external iron exchange, despite substantial tissue iron excess and accelerated internal iron transit.     

EEG during masturbation and ejaculation

The occurrence of a distinctive EEG pattern specifically related to sexual arousal and orgasm would provide a reliable and convenient means of identifying such events in the laboratory and would also provide clues to cerebral structures involved in the processes.EEG-polygraph recordings were obtained under rigorously controlled conditions in four normal male subjects during masturbation and ejaculation. The EEG data were subjected to both impressionistic and quantitative analyses. They showed no remarkable changes during the sequence of relevant physiological responses. The sole effect was a slight depression of alpha activity, a well-known nonspecific effect associated with changes in attention and arousal. Examination of the literature shows little agreement among reported results of studies of EEG changes during orgasm. It is likely that at least some reported changes were artifactual. It is concluded that the case for the existence of EEG changes specifically related to sexual arousal and orgasm remains unproven.     

Primary effusion lymphoma: a distinct clinicopathologic entity associated with the Kaposi's sarcoma-associated herpes virus

We recently discovered the Kaposi's sarcoma-associated herpes virus (KSHV/HHV-8) in an uncommon and unusual subset of AIDS-related lymphomas that grow mainly in the body cavities as lymphomatous effusions without an identifiable contiguous tumor mass. The consistent presence of KSHV and certain other distinctive features of these body cavity-based lymphomas suggest that they represent a distinct entity. We tested this hypothesis by investigating 19 malignant lymphomatous effusions occurring in the absence of a contiguous tumor mass for their clinical, morphologic, immunophenotypic, viral, and molecular characteristics, KSHV was present in 15 of 19 lymphomas. All four KSHV- negative lymphomatous effusions exhibited Burkitt or Burkitt-like morphology and c-myc gene rearrangements and, therefore, appeared to be Burkitt-type lymphomas occurring in the body cavities. In contrast, all 15 KSHV-positive lymphomatous effusions exhibited a distinctive morphology bridging large-cell immunoblastic lymphoma and anaplastic large-cell lymphoma, and all 12 cases studied lacked c-myc gene rearrangements. In addition, these lymphomas occurred in men (15/15), frequently but not exclusively in association with HIV infection (13/15), in which homosexuality was a risk factor (13/13), presented initially as a lymphomatous effusion (14/15), remained localized to the body cavity of origin (13/15), expressed CD45 (15/15) and one or more activation-associated antigens (9/10) in the frequent absence of B-cell- associated antigens (11/15), exhibited clonal immunoglobulin gene rearrangements (13/13), contained Epstein-Barr virus (14/15), and lacked bcl-2, bcl-6, ras and p53 gene alterations (13/15). These findings strongly suggest that the KSHV-positive malignant lymphomatous effusions represent a distinct clinicopathologic and biologic entity and should be distinguished from other malignant lymphomas occurring in the body cavities. Therefore, we recommend that these malignant lymphomas be designated primary effusion lymphomas (PEL), rather than body cavity-based lymphomas, since this term describes them more accurately and avoids their confusion with other malignant lymphomas that occur in the body cavities. We further recommend that these PEL be considered for inclusion as a new entity in the Revised European- American Lymphoma Classification.     

Cryptic structural lesions in refractory partial epilepsy: MR imaging and CT studies

Results of contrast material-enhanced computed tomography (CT) and T2-weighted spin-echo magnetic resonance (MR) imaging were correlated with pathologic findings in 25 patients treated surgically for refractory partial epilepsy. Of 12 lesions present, ten (83%) were detected by MR imaging and seven (58%) by CT scanning. Of nine low-grade gliomas, eight were detected by MR imaging and four by CT scanning. One posttraumatic scar and one case of temporal lobe atrophy were better demonstrated by MR imaging. A small, thrombosed arteriovenous malformation was the only lesion detected by CT scanning but not by MR imaging. No lesions were detected in 13 patients with mild gliosis and one patient with a 1.2-cm grade 1 astrocytoma. Although more sensitive than CT for detection of structural lesions in patients with refractory partial epilepsy, MR imaging resulted in a 25% false-negative diagnostic rate when a repetition time of 2,000 msec and echo time of 60 msec were used. Multi-echo imaging with at least one long echo time may be needed to increase the sensitivity of MR imaging in these patients.     

Encapsidated adenovirus mini-chromosome-mediated delivery of genes to the retina: application to the rescue of photoreceptor degeneration

First (DeltaE1/E3) and second (DeltaE1+DeltaE2/E3/E4) generation adenovirus (Ad) vectors have been shown previously to be of limited use in the treatment of human genetic diseases due to the induction of a host cytotoxic T-cell mediated immune response against virally expressed genes. In addition, a limited cloning capacity of approximately 8 kb does not cater for the incorporation of large upstream sequences essential for regulated tissue-specific expression or inclusion of multiple gene-expression cassettes. In this study we have exploited our recently developed Ad-based vector, the encapsidated adenovirus mini-chromosome (EAM) from which all of the viral genes have been deleted. EAMs contain only the inverted terminal repeats required for replication and five cis -acting Ad encapsidation signals necessary for packaging. We have shown previously that EAMs can efficiently transduce a variety of cell types in vitro. In this study we demonstrate that EAMs can transduce and rescue cells from the neurosensory retina in vivo. EAM-mediated delivery of the beta subunit of cyclic GMP phosphodiesterase (PDE) cDNA to mice affected with retinal degeneration (rd) allows prolonged transgene expression and rescue of rod photoreceptor cells. RT-PCR analysis from the injected retina indicates that transgene products are present for at least 18 weeks post-injection. Both the alpha and beta subunits of PDE could be detected up to 90 days postnatal in EAM-injected rd retina by western analysis. A maximal PDE activity of 150 nm/min/mg was detected at 33 days postnatal. Examination of outer nuclear thickness showed significant differences up to 12 weeks post-injection. These results demonstrate an improved level of rescue over first-generation adenoviral vectors and suggest the possibility of successful EAM- mediated treatment of some retinal diseases in humans.      

Changes in symptom scores as a potential clinical endpoint for studies of cystic fibrosis pulmonary exacerbation treatment

Introduction: Symptom improvement was assessed as changes in the Chronic Respiratory Infection Symptom Score (CRISS) during intravenous antimicrobial exacerbation treatments among subjects from study NCT02109822.Methods: Median daily CRISS reduction (i.e., improvement) and covariates associated with CRISS reduction by Day 14 were assessed by logistic regression.Results: Among 173 subjects, median baseline CRISS was 49 [IQR 41, 56]; 93.6% had a CRISS reduction of ≥11 (minimal clinically important difference); median time to –11 reduction was 2 days [95% CI 2, 3]. The greatest median CRISS difference from baseline, on Day 17, was –26 [–29, –23]. Odds of –26 CRISS change by Day 14 were greater in subjects with higher baseline CRISS (P=.006) and younger ages (P=.041).Conclusions: CRISS response has good dynamic range and may be a useful efficacy endpoint for PEx interventional trials. The optimal use of CRISS change as an endpoint remains uncharacterized.     

Increased plasma thyroid stimulating hormone in treated congenital hypothyroidism: relation to severity of hypothyroidism, plasma thyroid hormone status, and daily dose of thyroxine

Plasma thyroid stimulating hormone (TSH) concentrations obtained during the first four years of treatment in 418 children with congenital hypothyroidism, identified by neonatal screening, were examined in relation to paired measurements of plasma thyroxine (n = 1945), free thyroxine (n = 836), triiodothyronine (n = 480), and free triiodothyronine (n = 231), and estimated daily dose of thyroxine at the time of blood sampling. Overall, plasma TSH was above 7 mU/l in 1280 out of 2960 samples (43%); the percentage was not related to severity of hypothyroidism at diagnosis. Mean values for thyroxine and free thyroxine, and to a lesser extent free triiodothyronine, were consistently lower in samples with TSH concentrations over 7 mU/l and this was the case in patients with either severe or less severe hypothyroidism. Raised TSH concentrations were also associated with lower mean doses of thyroxine (micrograms/kg/day) but here the mean doses of thyroxine in children with severe hypothyroidism were higher than in the children with less severe hypothyroidism. The mean dose of thyroxine associated with low/normal TSH values was highest in the first 6 months and fell progressively. Thyroxine dose was significantly related to thyroxine and free thyroxine concentrations but not to triiodothyronine and free triiodothyronine and the latter appeared to be of limited value as measures of plasma thyroid hormone status during treatment.     

Sons of Alcoholics Report Greater Hangover Symptoms than Sons of Nonalcoholics: A Pilot Study

We investigated alcohol-induced hangovers among college men at high and low risk for alcoholism. Thirteen sons of alcoholics reported significantly (p less than 0.001) greater hangover symptoms in the past year than 25 sons of nonalcoholics. The two groups reported comparable quantity-frequency of recent drinking. To the extent that hangover represents an acute withdrawal syndrome to alcohol, this raises the question of whether sons of alcoholics are "dependence-prone."