Accuracy and clinical performance of a continuous intra-arterial blood- gas monitoring system during thoracoscopic surgery

Accuracy and performance of the only currently available intra-arterial blood-gas monitoring system (Paratrend 7, PT7) were assessed in 23 patients during thoracoscopic surgery using one-lung ventilation. Over a wide range of values for arterial PO2 (6.1-61.1 kPa), PCO2 (4.1-9.5 kPa) and pH (7.19-7.50), 138 arterial blood-gas values obtained by PT7 were compared with corresponding in vitro laboratory blood-gas measurements. We found good clinical performance with the PT7 and good agreement between PT7 values and in vitro measurements for arterial PO2 (bias (1.96 SD) = 0.38 (9.52) kPa), PCO2 (0.31 (0.76) kPa) and pH (- 0.017 (0.065)). Also, the bias for sequential changes between two, consecutive times was not significantly different from the ideal value of 0. We conclude that the PT7 is helpful in monitoring patients during thoracoscopy.      

Roving lateral eye movements in coma. A clinical-pathological study

Five patients in deep coma due to extensive supratentorial lesions presented roving lateral eye movements (ping-pong gaze), distinguished by the fact that the eyes, after moving to one extreme of gaze, returned to the midline instead of to the opposite extreme. The phenomenon was reported recently by Reynard et al.

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Sommario Gli autori descrivono l'osservazione di movimenti oculari laterali tipo vagante (roving movements; ping-pong gaze) eseguita su 5 pazienti in coma profondo. È particolare il fatto che tali movimenti, iniziando da un estremo laterale si arrestano alla linea mediana in luogo di raggiungere il canto controlaterale. Tale fenomeno ha solo una precedente segnalazione (Reynard et al).

     

YAP1-MAML2-Rearranged Poroid Squamous Cell Carcinoma (Squamoid Porocarcinoma) Presenting as a Primary Parotid Gland Tumor

Porocarcinoma (synonym: malignant eccrine poroma) is a rare aggressive carcinoma type with terminal sweat gland duct differentiation. The squamous variant of porocarcinoma is even less frequent and might be indistinguishable from conventional squamous cell carcinoma (SCC). We herein describe the first case of a carcinoma presenting as a primary parotid gland malignancy in a 24-year-old male without any other primary tumor. Total parotidectomy and neck dissection were performed followed by adjuvant chemoradiation. The patient remained alive and well 10 months after diagnosis. Histology showed keratinizing SCC infiltrating extensively the parotid gland with subtle poroid cell features. Oncogenic HPV infection was excluded by DNA-based testing. NGS analysis using the TruSight RNA fusion panel (Illumina) revealed a novel YAP1-MAML2 gene fusion. This gene fusion was reported recently in a subset of cutaneous porocarcinoma and poroma. This case of poroid SCC (or squamoid porocarcinoma) adds to the differential diagnosis of SCC presenting as parotid gland tumor and highlights the value of molecular testing in cases with unusual presentation.Electronic supplementary materialThe online version of this article (10.1007/s12105-020-01181-9) contains supplementary material, which is available to authorized users.     

Intermittent claudication due to ischaemia of the lumbosacral plexus

The distinct clinical syndrome of exercise induced ischaemia of the lumbosacral plexus is not a widely known cause for intermittent claudication. Eight patients with the mentioned syndrome were investigated clinically, neurophysiologically, and with imaging techniques. The clinical examination showed a typical exercise induced sequence of symptoms: pain, paraesthesia, and sensory and motor deficits. The underlying vascular conditions were high grade stenoses or occlusions of the arteries supplying the lumbosacral plexus. Spinal stenosis could be excluded in all cases. Five patients received successful interventional radiological therapy. The syndrome can be diagnosed clinically and successful therapy is possible by interventional radiology.     

CPCCOEt, a noncompetitive metabotropic glutamate receptor 1 antagonist, inhibits receptor signaling without affecting glutamate binding

Metabotropic glutamate receptors (mGluRs) are a family of G protein-coupled receptors characterized by a large, extracellular N-terminal domain comprising the glutamate-binding site. In the current study, we examined the pharmacological profile and site of action of the non-amino-acid antagonist 7-hydroxyiminocyclopropan[b]chromen-1a-carboxylic acid ethyl ester (CPCCOEt). CPCCOEt selectively inhibited glutamate-induced increases in intracellular calcium at human mGluR1b (hmGluR1b) with an apparent IC50 of 6.5 microM while having no agonist or antagonist activity at hmGluR2, -4a, -5a, -7b, and -8a up to 100 microM. Schild analysis indicated that CPCCOEt acts in a noncompetitive manner by decreasing the efficacy of glutamate-stimulated phosphoinositide hydrolysis without affecting the EC50 value or Hill coefficient of glutamate. Similarly, CPCCOEt did not displace [3H]glutamate binding to membranes prepared from mGluR1a-expressing cells. To elucidate the site of action, we systematically exchanged segments and single amino acids between hmGluR1b and the related subtype, hmGluR5a. Substitution of Thr815 and Ala818, located at the extracellular surface of transmembrane segment VII, with the homologous amino acids of hmGluR5a eliminated CPCCOEt inhibition of hmGluR1b. In contrast, introduction of Thr815 and Ala818 at the homologous positions of hmGluR5a conferred complete inhibition by CPCCOEt (IC50 = 6.6 microM), i.e., a gain of function. These data suggest that CPCCOEt represents a novel class of G protein-coupled receptor antagonists inhibiting receptor signaling without affecting ligand binding. We propose that the interaction of CPCCOEt with Thr815 and Ala818 of mGluR1 disrupts receptor activation by inhibiting an intramolecular interaction between the agonist-bound extracellular domain and the transmembrane domain.     

Long-lasting effect of early handling on the peripheral benzodiazepine receptor

The present study determined the impact of early handling (EH) in rats on behavioral response to environmental stress and on peripheral benzodiazepine receptor (PBR) binding characteristics (Bmax and Kd) in various organs. The behavioral consequences of EH in rats were expressed as increased exploratory activity in an open-field paradigm, when compared with nonhandled control rats. These findings are interpreted in terms of decreased emotionality. The biochemical consequences of EH, in both male and female rats, were expressed as the upregulation of PBR in the adrenal and kidney and the downregulation of gonadal (testis and ovary) PBR. It is possible that the long-lasting adrenal and renal changes in PBR expression in EH rats may enable better regulation of the hypothalamic-pituitary-adrenal axis, renin-angiotensin system, and autonomic nervous system responses to stress in adulthood. The significance of the EH-induced reduction in gonadal PBR for gonadal activity in adulthood is as yet unclear.     

Molecular heterogeneity of sporadic adult Burkitt-type leukemia/lymphoma as revealed by PCR and cytogenetics: correlation with morphology, immunology and clinical features.

Chromosomal translocations involving the MYC oncogene are a hallmark of Burkitt lymphoma but they are only found in a varying frequency in mature Burkitt-type acute lymphoblastic leukemia (B-ALL). We have investigated samples of 56 sporadic Burkitt leukemia/lymphoma patients for the translocations t(8;14)(q24;q32), t(2;8)(p11;q24) and t(8;22)(q24;q11). Long PCR was used for detecting the immunoglobulin heavy chain (IgH) translocation and cytogenetics and/or fluorescence in situ hybridization for detecting the 'variant' MYC translocations. A total of 29 samples (51.8%) were t(8;14)-positive by long PCR. Approximately one-third had a chromosomal breakpoint in the IgH joining region while the others had breakpoints in the IgH switch regions. Among them were two cases with a previously unreported MYC translocation into the IgE switch region. Long PCR was more reliable compared to conventional cytogenetics for detecting the t(8;14). Epstein-Barr virus was detected in high copy number in two (3.6%) t(8;14)-positive cases by real-time quantitative PCR. Human herpesvirus 8 was not detected in any case by nested PCR. A typical L3 or L3-compatible cytomorphology was highly predictive (>80%) but not specific of a MYC translocation. A total of 34 patients were treated according to the GMALL B-ALL therapy protocols and there was no significant difference in overall survival between patients with or without t(8;14).     

Foscarnet and ganciclovir combination therapy for CMV disease in HIV-infected patients

Summary An open prospective trial of combined ganciclovir and foscarnet therapy for 3 weeks was initiated in 14 episodes of severe CMV-disease in 13 HIV-infected patients (all CDC class IV, age 30–42, median 34 years, CD4+ cell count 0–80, median 10/µl). In seven episodes of gastrointestinal disease (five colitis, two esophagitis) remission of symptoms and mucosal changes was achieved in five. In seven episodes of retinitis, scarring was achieved in six. Renal toxicity was seen in two patients, moderate hematologic toxicity in eight patients. Overall efficacy was comparable to monotherapy; no new toxicities were seen with the combination of these two drugs.

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Kombinationstherapie mit Ganciclovir und Foscarnet bei schwerer CMV-Erkrankung bei HIV-infizierten Patienten

Zusammenfassung In 14 Episoden einer CMV-Erkrankung bei 13 HIV-infizierten Patienten wurde eine Kombinationstherapie mit Ganciclovir und Foscarnet in einer offenen, prospektiven, nicht randomisierten Studie durchgeführt. Alle Patienten (n=13, Alter 30–42, Median 34 Jahre; CD4+Lymphozyten 0–80, Median 10/µl; alle Stadium IV CDC) wurden über 3 Wochen mit 2 × 5 mg/kg/d Ganciclovir und 2 × 90 mg/kg/d Foscarnet behandelt. In sieben Episoden einer gastrointestinalen CMV-Erkrankung (Colitis fünf, Ösophagitis zwei) wurde eine Remission in fünf Episoden erzielt, bei CMV-Retinitis in sechs von sieben Fällen. Nephrotoxizität trat bei zwei Patienten auf, mäßige Hämatotoxizität bei acht Patienten, sämtlich reversibel. Die Wirksamkeit der Therapie ist ähnlich der Monotherapie, die Nebenwirkungen sind additiv.