Assessment of ventricular function by radionuclide angiography in patients receiving 4′-epidoxorubicin and mitoxantrone

Summary Serial assessment of ventricular function by means of radionuclide angiography was performed in 50 patients with malignant neoplasms who received either 4-epidoxorubicin or mitoxantrone for longer than 3 months.In 9 of 30 patients give 4-epidoxorubicin, a decrease of 10% in the left ventricular ejection fraction (LVEF) was documented at doses of 143–1200 mg/m². Two patients developed clinical signs of cardiotoxicity at a dose of >1000 mg/m².In 6 of 20 patients given mitoxantrone a decrease of 10% in the LVEF occurred at doses of 26–98 mg/m².This study was supported in part by a grant from the National Cancer Association of South Africa     

Anatomical disassociation of amphetamine's rewarding and aversive effects: An intracranial microinjection study

Amphetamine has rewarding properties in some behavioral paradigms, such as self-administration and conditioned place preference (CPP), but an aversive component is also apparent when the drug is tested with the conditioned taste aversion (CTA) paradigm. The persent study was an attempt to determine the neuroanatomical substrates of the drug's rewarding and aversive effects. Previous evidence suggested that amphetamine's stimulation of activity in dopaminergic synapses is critical for both effects. Amphetamine was therefore micro-injected bilaterally (10 g/0.5 l per side) into six different dopaminergic sites, each in a different group of animals: the medial prefrontal cortex, nucleus accumbens, anteromedial caudate nucleus, lateroventral caudate nucleus, amygdala, and the region subjacent to the area postrema (AP region). The effects of these injections in both the taste and place conditioning paradigms were examined in separate experiments. Of the six sites, a significant CPP was observed only with accumbens injections and a significant CTA was observed only with AP region injections. It was concluded that the accumbens plays a primary role in mediating the rewarding effects of amphetamine and that the AP region plays a primary role in mediating the CTA. This constitutes an anatomical disassociation of amphetamine's rewarding and aversive effects. The differential associative bias of place-reward and taste-aversion learning apparent in the results is discussed. Offprint requests to: N.M. White     

The relationship between stereotypy and memory improvement produced by amphetamine

This study examined the possibility that amphetamine-induced stereotypy and facilitation of memory consolidation are both mediated by amphetamine's stimulation of dopaminergic activity in the caudate nucleus. In the first experiment, rats were given pairings of a tone and a shock followed by SC amphetamine (2 mg/kg). The amount of stereotypy and increased locomotor activity produced by the injection were measured immediately. Retention of the tone-shock association was evaluated 48 h later by observing the ability of the tone to suppress drinking. The degree of retention was significantly correlated with the amount of stereotypy but not with the amount of locomotion previously measured. In the second experiment, amphetamine was microinjected into the caudate nucleus (10 g/l) and its ability to produce the same three behavioral effects was examined. These injections produced increased stereotypy and improved retention, but no increase in locomotion. The correlation of memory facilitation with stereotypy and the fact that both were produced by intracaudate amphetamine suggest that they may be mediated by the same neuropharmacological substrate, namely amphetamine-induced release of dopamine in the caudate.     

Alcoholic and Non-Alcoholic Beer Modulate Plasma and Macrophage microRNAs Differently in a Pilot Intervention in Humans with Cardiovascular Risk

Beer is a popular beverage and some beneficial effects have been attributed to its moderate consumption. We carried out a pilot study to test if beer and non-alcoholic beer consumption modify the levels of a panel of 53 cardiometabolic microRNAs in plasma and macrophages. Seven non-smoker men aged 30–65 with high cardiovascular risk were recruited for a non-randomised cross-over intervention consisting of the ingestion of 500 mL/day of beer or non-alcoholic beer for 14 days with a 7-day washout period between interventions. Plasma and urine isoxanthohumol were measured to assess compliance with interventions. Monocytes were isolated and differentiated into macrophages, and plasma and macrophage microRNAs were analysed by quantitative real-time PCR. Anthropometric, biochemistry and dietary parameters were also measured. We found an increase in plasma miR-155-5p, miR-328-3p, and miR-92a-3p after beer and a decrease after non-alcoholic beer consumption. Plasma miR-320a-3p levels decreased with both beers. Circulating miR-320a-3p levels correlated with LDL-cholesterol. We found that miR-17-5p, miR-20a-5p, miR-145-5p, miR-26b-5p, and miR-223-3p macrophage levels increased after beer and decreased after non-alcoholic beer consumption. Functional analyses suggested that modulated microRNAs were involved in catabolism, nutrient sensing, Toll-like receptors signalling and inflammation. We concluded that beer and non-alcoholic beer intake modulated differentially plasma and macrophage microRNAs. Specifically, microRNAs related to inflammation increased after beer consumption and decreased after non-alcoholic beer consumption.     

Comparison of benign and malignant insulinoma

BackgroundHow malignant insulinomas present relative to benign insulinomas is unknown.MethodsA single-institution retrospective study identified patients with insulinoma. Malignancy was defined by distant metastases, positive lymph node(s), T stage of 4, direct invasion into surrounding peripancreatic tissue, or presence of lymphovascular invasion. Wilcoxon Rank Sum tests and Kaplan-Meier analysis were used.ResultsA total of 311 patients were identified: 51 malignant and 260 benign. Patients with malignant insulinoma presented with higher levels of insulin, proinsulin, and c-peptide. Malignant lesions were larger: 4.2 ± 3.2 vs 1.8 ± 0.8 cm in benign lesions, p < 0.01. Overall survival at 5 years was 66.8% vs 95.4% for malignant and benign insulinoma respectively, p < 0.01.ConclusionsLarger size of insulinoma and increased serum β-cell polypeptide concentrations were associated with malignancy. Malignant insulinoma has poorer survival. Further work-up to rule out malignancy may be indicated for larger pancreatic lesions and for patients with higher pre-operative insulin and pro-insulin.     

Lessons learned from lower urinary tract complications of anorectoplasty for imperforate anus with rectourethral/rectovesical fistula: Laparoscopy-assisted versus posterior sagittal approaches

PurposeTo report the sequelae of and preventive strategies for selected lower urinary tract (LUT) complications, i.e., posterior urethral diverticulum (PUD), intraoperative LUT injuries, postoperative dysuria, and fistula recurrence in male imperforate anus (IA) with rectourethral/rectovesical (RU/RV) fistula after laparoscopy-assisted anorectoplasty (LAARP) or posterior sagittal anorectoplasty (PSARP).Methods153 boys with IA and RU/RV fistula treated 1986–2019 by LAARP (n = 56) or PSARP (n = 97) at two unrelated institutes were studied retrospectively.ResultsAfter mean follow-up of 17.0 years (range: 36.5 days-32.0 years), the overall incidences of LUT complications were: LAARP (6/56; 10.7%); PSARP (7/97; 7.2%); p = 0.55, comprising PUD: LAARP (n = 5), PSARP (n = 0); p = 0.006; injuries: LAARP (n = 0), PSARP (n = 5); p = 0.16; dysuria: LAARP (n = 1), PSARP (n = 1); p>0.999; and recurrence: LAARP (n = 0), PSARP (n = 1); p>0.999. Mean onset of PUD was 5.1 years (range: 1.0–15.1 years). Treatment: PUD: surgery (n = 2/5), conservative (n = 3/5); injuries: intraoperative repair (n = 5/5); dysuria: conservative (n = 2/2), and recurrence: redo PSARP (n = 1/1).ConclusionsStrategies devised to improve dissection accuracy resolved the specific technical issues causing LUT complications (remnant RU fistula dissection in LAARP and blind posterior access in PSARP). Currently, the incidence of new cases of PUD and LUT injuries is zero.Level of Evidence: Level III