Cutis Marmorata Telangiectatica Congenita Associated with a Double Aortic Arch

Abstract: We report a patient with cutis marmorata telangiectatica with the hitherto unreported anomaly of a double aortic arch. The presence of two major vascular anomalies in this patient may be secondary to a developmental defect of the mesoderm during embryogenesis.     

Phase I and pharmacologie study of liposomal daunorubicin (DaunoXome)

Summary We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial doseescalation steps from 10 to 60 mg/m². At 80 mg/m², two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m². Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m² in previously treated and 120 mg/m² of DaunoXome in previously untreated patients with solid tumors.EDW is supported in part by ACS award 92-14-1     

Simultaneous Pulmonary Leiomyosarcoma and Leiomyoma in Pediatric HIV Infection

The case of a 7-year-old girl with acquired immunodeficiency syndrome treated for 5 years with AZT and intravenous gamma globulin is reported. Shortly before her demise she developed a pulmonary leiomyosarcoma and leiomyoma. Does prolonged survival in pediatric acquired immune deficiency syndrome increase the incidence of secondary malignancies?     

A comprehensive survey for polymorphisms in the bovine IFN-gamma gene reveals a highly polymorphic intronic DNA sequence allowing improved genotyping of Bovinae.

This study aimed to identify interferon-gamma (IFN-gamma) gene variants in cattle for diagnostic purposes. Therefore, the entire bovine IFN-gamma gene (BoIFNG) and 2605 bp of its promoter DNA were sequenced. The BoIFNG DNA sequence conforms to the published part of Bo-IFN-gamma cDNA. Primer extension experiments show the presence of a 5' extension of exon 1 by 42 nucleotides (nt). One SINE element (Bov-A2) is located in the 5'-region, and two SINE elements (Bov-tA, Bov-B) are contained in the 3'-region of BoIFNG. The variants were detected by comparative sequence analysis of PCR amplicons from different bovine species. Four polymorphic mononucleotide repeats are situated in the promoter and in intron 1. Four distinct series of single nucleotide polymorphisms (SNP) were found in functionally important regions of BoIFNG. The region between the two intron 1 microsatellites contains the highest density of SNPs in Bos taurus breeds. One G-T transversion in the coding region of exon 1 causes a Gly(14) to Val(14) exchange in the BoIFNG signal peptide of different bovine species. A G-A transition in exon 2 encodes a Ser(19) to Asn(19) change in the mature protein of the Tibetan yak. Genotyping of randomly sampled Holstein Friesian cows at selected SNPs and of both intron 1 microsatellites revealed two dominant BoIFNG microhaplotypes. The detected SNPs improve the recently reported genotyping system of cattle.     

Testing for skin sensitization according to the notification procedure for new chemicals: the Magnusson and Kligman test

The notification procedure for new chemicals in the European Union (called the Chemicals Act in Germany) requires a skin sensitization test when the amount of a new chemical produced exceeds 100 kg/year. The preferred test is that of Magnusson and Kligman; more than 90% of the tests submitted are performed with it. Though the Magnusson and Kligman test is described in the literature, and in the test guidelines of the European Union and of the OECD, discrepancies do occur in the performance of the test between test laboratories. In this paper, recommendations are given for standardized performance of the Magnusson and Kligman test.     

Enduring effects of prenatal cocaine exposure on selective attention and reactivity to errors: evidence from an animal model

Adult Long-Evans rats, exposed prenatally to 1 of 4 doses of cocaine (0.0,0.5,1.0, or 3.0 mg/kg iv), were tested on a 3-choice visual attention task with an olfactory distractor presented unpredictably on one third of the trials. The performance of all 3 cocaine-exposed groups was significantly more disrupted than that of controls by the presentation of distractors. Results demonstrate that prenatal cocaine exposure increases susceptibility to distractors, using a task specifically designed to measure this function. In addition, the present study revealed that individuals exposed to cocaine in utero exhibit greater performance disruption after an error than controls, in certain types of tasks. Both areas of dysfunction, impaired selective attention and impaired arousal regulation, have important functional consequences in humans, possibly affecting the school performance and social development of cocaine-exposed children.     

Influence of Various Immunomodulators on the Induction of Experimental Autoimmune Encephalomyelitis in Lewis Rats

The effect of various immunomodulators on the induction of experimental autoimmune encephalomyelitis (EAE) is evaluated in the Lewis rat. Bordetella pertussis (BP) is the optimal inductor of EAE in this rat strain. Treatment of the animals with BP either before or after or simultaneously with guinea-pig spinal cord preparation (GpSC) resulted in an EAE about two weeks thereafter. Additional injection of living BCG, of CFA, IFA (incomplete Freund's adjuvant) or Vibrio cholerae neuraminidase (VCN) did not augment or mitigate the effect induced by BP or GpSC. Living BCG, IFA, VCN or Corynebacterium parvum (CP) did not induce EAE when given in combination with GpSC but without BP. CFA combined with GpSC only occasionally induced EAE. However, EAE could be induced by the combination of CFA and GpSC or IFA and GpSC in a part of the animals tested if they had been pretreated or simultaneously been injected with living BCG by intravenous route. EAE could not be enhanced by the additional injection of VCN. Surprisingly, most of the animals peracutely died after injection of CFA and BP in combination with GpSC when they had been pretreated with CP. This effect was most pronounced when pretreatment was done on day -4. No acute effect could be seen when CP was given simultaneously to CFA, BP and GpSC. Animals which did not peracutely succumb developed EAE similarly as those in the positive control groups. CP treatment simultaneously with BP but without CFA resulted in a reduction of the EAE specific mortality. This reduction could not be seen if treatment with CP was done after injection of GpSC and BP.     

Duodenal ulcer

In 1958 the Yale freshman class gave blood samples as part of a study intended to determine the predictive value of plasma pepsinogen (PP) for the subsequent development of duodenal ulcer (DU). We report a long-term follow-up of this cohort. A selfadministered questionnaire designed to ascertain information about the development of peptic ulcers, and the presence of risk factors was mailed to 861 subjects with active addresses. A second questionnaire was mailed to each respondent's physician(s) to verify the diagnosis of DU. Completed questionnaires were returned, after three mailings, by 604 (70%) of the subjects. They reported 18 documented DUs, 15 since 1958, for an incidence of 1.1/1000 person years. Only smoking (P<0.05) and undergraduate physical inactivity (P<0.01) were identified as risk factors for DU. Family history; blood type; blood antigen secretor status; ingestion of coffee, alcohol, milk, salicylates, soda, or tea; and COPD were not identified as risk factors for DU. Patients with DU had higher mean PP values than those who did not (391.6±99.6 vs 346.6±106.7, mean ±sd) but this was not statistically significant (P>0.05). The predictive value of an elevated PP(>450) for the development of DU was 7.9%, but a low or normal PP predicted the absence of a DU in 97.5% of subjects over a 22-year span. We conclude that in a selected population followed for 22 years there is a low incidence of DU, supporting the general belief that duodenal ulcer is declining, that smoking and undergraduate physical inactivity are risk factors for duodenal ulcer, and that a low or normal PP may be useful as a predictor for a low susceptibility to duodenal ulcer disease.Dr. J. Chuong acknowledges the support of the Robert Wood Johnson Clinical Scholar Program, and the Daland Fellowship in Clinical Medicine of the American Philosophical Society.     

The effects of a 5-HT1 receptor ligand isapirone (TVX Q 7821) on 5-HT synthesis and the behavioural effects of 5-HT agonists in mice and rats

The effects of 2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)-butyl)-1,2-benzoisothiazol-3(2H)one-1,1-dioxide hydrochloride (isapirone, TVX Q 7821), a putative 5-HT₁ receptor antagonist, has been studied on various models of 5-HT receptor sub-type function. In mice TVX Q 7821 produced a dose-dependent inhibition of the hypothermia induced by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) with an ED₅₀ of 5.3 mg/kg suggesting that TVX Q 7821 was an antagonist of the presynaptic (possibly somato-dendritic) 5-HT_1A receptor. TVX Q 7821 did not alter the locomotor response to the suggested 5-HT_1B agonist RU 24969. The rate of mouse brain 5-HT synthesis was accelerated by TVX Q 7821 (10 mg/kg). 5-HT₂ receptor-mediated head twitch behaviour induced by precursor loading with 5-HTP was unaffected by TVX Q 7821 (10 mg/kg) pretreatment 75 min earlier, but the head-twitch induced by the agonist 5-methoxy-N,N-dimethyltryptamine was enhanced by prior treatment with TVX Q 7821.In rats the hypothermia induced by 8-OH-DPAT was partially antagonised by TVX Q 7821 while the behavioural serotonin syndrome induced by 8-OH-DPAT (a possible post-synaptic 5-HT_1B-mediated effect) was unaffected by TVX Q 7821 as was the locomotion induced by RU 24969.The data suggest that TVX Q 7821 is a good presynaptic 5-HT_1A antagonist in mice, as indicated by the 8-OH-DPAT-induced hypothermia and 5-HT synthesis rate studies. It did not antagonise 5-HT_1B-mediated behaviour in mice or rats and appeared to have an antagonist action at pre- but not post-synaptic 5-HT_1A receptors in rats. Offprint requests to: G.M. Goodwin