Mortality in major affective disorder: relationship to subtype of depression

A total of 219 inpatients with a DSM-III diagnosis of major depression, 150 women and 69 men, were followed prospectively for 3–10 years and mortality was recorded. The patients were previous participants in psychopharmacological multicenter trials, which were carried out for the purpose of comparing the antidepressant effect of newer 5-HT reuptake inhibitors with that of the tricyclic antidepressant drug, clomipramine. The study comprised patients with a total Hamilton Rating Scale for Depression score of ≥ 18 and/or a Hamilton subscale score of ≥ 9. Diagnostic classification according to the Newcastle I Scale in endogenous and nonendogenous depression was performed. The observed mortality was significantly greater than that expected. The increased mortality was essentially due to suicides and mainly found among women. Patients scored as nonendogenously depressed had a significantly higher suicide rate than endogenously depressed patients. The excess number of suicides in the nonendogenous group largely occurred within the first year of observation. No association was found between response to the antidepressant treatment in the trial and the suicide risk in the first 3 years of observation.     

Keratin immunohistochemistry in renal cell carcinoma subtypes and renal oncocytomas: a systematic analysis of 233 tumors

Keratin immunohistochemistry represents a widely applied differential diagnostic tool in surgical pathology. To investigate the value of keratin subtyping for the diagnosis among histological subtypes of renal cell carcinoma and oncocytomas, we performed a detailed immunohistochemical study, applying 22 different monoclonal keratin antibodies on a large series of 233 renal tumors [125 conventional, 22 chromophobe, and 20 papillary (12 type-1, 8 type-2 tumors) cancers and 66 oncocytomas] using a tissue microarray technique. Immunoreactivity for keratin 7, 8, 18, and 19 was present in all tumor entities, albeit in varying quantities. With antibodies directed against keratins 8 and 18, oncocytomas showed a distinct perinuclear and punctate dot-like pattern, which was not observed in renal cancer specimens. The only tumors showing immunoreactivity for keratin 20 were two type-2 papillary cancers. All other monospecific keratin antibodies yielded consistently negative results. Overall, in contrast to some recent publications, keratin subtyping generally appeared to be of additional value only for the differentiation of renal epithelial tumors. Hence, with respect to differential diagnostic value, Hales colloidal iron stain and vimentin immunostaining are still the most useful tools in renal tumor pathology.     

Genetic Variability of HIV-1 Protease from Nigeria and Correlation with Protease Inhibitors Drug Resistance

In Nigeria, the most populous country in Africa, the characterization of HIV-1 strains has been limited. In this study we evaluated the genetic diversity of the protease coding region, one of the anti-retroviral therapy target, and investigated the presence of mutations related to resistance to HIV protease inhibitors. We analyzed samples collected during 1996 and all patients were anti-retroviral drug na¨ves. Ten samples were evaluated by sequencing of the protease gene. The majority, 80%, were classified as subtype A and the two others were unclassified-divergent strains, something in between A and G subtypes. The gag region from these outliners were sequenced and the phylogenetic analysis classified them as subtype G. The protease amino acid consensus sequence of the Nigerian subtype A are in complete agreement with the consensus A differing from the USA subtype B consensus in 10 positions (L10V, I13V, K14R, I15V, K20I, M36I, R41K, P63L, H69K and L89M).The secondary substitutions associated with protease inhibitor resistance were observed in all Nigerian sequences at the positions L10V, M36I and L89M. The majority of sequence variation was concentrated in the interval between aminoacids 70–90 where the protease substrate binding region is located.     

HLA-A*02 allele frequencies and haplotypic associations in Koreans

We have investigated the frequencies of HLA-A*02 alleles and their haplotypic associations with HLA-B and -DRB1 loci in 439 healthy unrelated Koreans, including 214 parents from 107 families. All of the 227 samples (51.7%) typed as A2 by serology were analyzed for A*02 alleles using polymerase chain reaction (PCR)-low ionic strength-single-strand conformation polymorphism (LIS-SSCP) method. A total of six different A*02 alleles were detected (A*02 allele frequency 29.6%): A*0201/9 (16.6%), *0203 (0.5%), *0206 (9.3%), *0207 (3.0%), and one each case of *0210 and *02 undetermined type. Two characteristic haplotypes showing the strongest linkage disequilibrium were A*0203-B38-DRB]*1502 and A*0207-B46-DRB1*0803. Besides these strong associations, significant two-locus associations (P<0.001) were observed for A*0201 with B61, DRB1*0901 and DRB1*1401, and for A*0206 with B48 and B61. HLA haplotypes carrying HLA-A2 showed a variable distribution of A*02 alleles, and all of the eight most common A2-B-DR haplotypes occurring at frequencies of > or =1% were variably associated with two different A*02 alleles. These results demonstrate that substantial heterogeneity is present in the distribution of HLA-A*02 alleles and related haplotypes in Koreans.     

The Spectrum of Malnutrition/Cachexia/Sarcopenia in Oncology According to Different Cancer Types and Settings: A Narrative Review

Nutritional status in oncological patients may differ according to several modifiable and non-modifiable factors. Knowledge of the epidemiology of malnutrition/cachexia/sarcopenia may help to manage these complications early in the course of treatment, potentially impacting patient quality of life, treatment intensity, and disease outcome. Therefore, this narrative review aimed to critically evaluate the current evidence on the combined impact of tumor- and treatment-related factors on nutritional status and to draw some practical conclusions to support the multidisciplinary management of malnutrition in cancer patients. A comprehensive literature search was performed from January 2010 to December 2020 using different combinations of pertinent keywords and a critical evaluation of retrieved literature papers was conducted. The results show that the prevalence of weight loss and associated symptoms is quite heterogeneous and needs to be assessed with recognized criteria, thus allowing a clear classification and standardization of therapeutic interventions. There is a large range of variability influenced by age and social factors, comorbidities, and setting of cures (community-dwelling versus hospitalized patients). Tumor subsite is one of the major determinants of malnutrition, with pancreatic, esophageal, and other gastroenteric cancers, head and neck, and lung cancers having the highest prevalence. The advanced stage is also linked to a higher risk of developing malnutrition, as an expression of the relationship between tumor burden, inflammatory status, reduced caloric intake, and malabsorption. Finally, treatment type influences the risk of nutritional issues, both for locoregional approaches (surgery and radiotherapy) and for systemic treatment. Interestingly, personalized approaches based on the selection of the most predictive malnutrition definitions for postoperative complications according to cancer type and knowledge of specific nutritional problems associated with some new agents may positively impact disease course. Sharing common knowledge between oncologists and nutritionists may help to better address and treat malnutrition in this population.     

Subtype‐specific differences in transmission cluster dynamics of HIV‐1 B and CRF01_AE in New South Wales,Australia

IntroductionThe human immunodeficiency virus 1 (HIV‐1) pandemic is characterized by numerous distinct sub‐epidemics (clusters) that continually fuel local transmission. The aims of this study were to identify active growing clusters, to understand which factors most influence the transmission dynamics, how these vary between different subtypes and how this information might contribute to effective public health responses.MethodsWe used HIV‐1 genomic sequence data linked to demographic factors that accounted for approximately 70% of all new HIV‐1 notifications in New South Wales (NSW). We assessed differences in transmission cluster dynamics between subtype B and circulating recombinant form 01_AE (CRF01_AE). Separate phylogenetic trees were estimated using 2919 subtype B and 473 CRF01_AE sequences sampled between 2004 and 2018 in combination with global sequence data and NSW‐specific clades were classified as clusters, pairs or singletons. Significant differences in demographics between subtypes were assessed with Chi‐Square statistics.ResultsWe identified 104 subtype B and 11 CRF01_AE growing clusters containing a maximum of 29 and 11 sequences for subtype B and CRF01_AE respectively. We observed a > 2‐fold increase in the number of NSW‐specific CRF01_AE clades over time. Subtype B clusters were associated with individuals reporting men who have sex with men (MSM) as their transmission risk factor, being born in Australia, and being diagnosed during the early stage of infection (p < 0.01). CRF01_AE infections clusters were associated with infections among individuals diagnosed during the early stage of infection (p < 0.05) and CRF01_AE singletons were more likely to be from infections among individuals reporting heterosexual transmission (p < 0.05). We found six subtype B clusters with an above‐average growth rate (>1.5 sequences / 6‐months) and which consisted of a majority of infections among MSM. We also found four active growing CRF01_AE clusters containing only infections among MSM. Finally, we found 47 subtype B and seven CRF01_AE clusters that contained a large gap in time (>1 year) between infections and may be indicative of intermediate transmissions via undiagnosed individuals.ConclusionsThe large number of active and growing clusters among MSM are the driving force of the ongoing epidemic in NSW for subtype B and CRF01_AE.     

胆道结石术后继发急性胆管炎病原菌及sCD14-ST和IL-8的诊断价值

目的探讨胆道结石术后继发急性胆管炎病原菌及可溶性CD14亚型(sCD14-ST)、白细胞介素-8(IL-8)的诊断价值。方法选择海南医学院第一附属医院2017年1月-2019年6月收治的胆道结石术后继发急性胆管炎患者62例作为研究对象,纳入研究组,选择同期医院收治的胆道结石术后未继发急性胆管炎的患者60例设为对照组;对研究组患者病原菌进行统计;比较不同急性胆管炎程度、不同预后结局患者血清sCD14-ST、IL-8水平;采用受试者工作特征曲线评估血清sCD14-ST、IL-8水平对于患者不良预后的诊断价值。结果 62例患者共培养分离病原菌67株,其中革兰阴性菌43株占64.18%,革兰阳性菌21株占31.34%,真菌3株占4.48%,以大肠埃希菌为主;重度急性胆管炎患者血清sCD14-ST、IL-8分别为(91.38±25.67)pg/ml、(45.28±13.61)pg/ml高于中度患者分别为(74.34±19.65)pg/ml、(32.06±10.44)pg/ml及轻度患者(P均<0.001),中度患者血清sCD14-ST、IL-8水平高于轻度患者(P均<0.001);预后不良患者急性胆管炎血清sCD14-ST、IL-8分别为(89.84±25.09)pg/ml、(41.94±12.28)pg/ml高于预后良好患者(P<0.05);sCD14-ST、IL-8对胆道结石术后急性胆管炎患者预后的截断值分别为65.65、29.31 pg/ml,其曲线下面积分别为0.841、0.768。结论胆道结石术后继发急性胆管炎病原以革兰阴性菌为主;运用血清sCD14-ST、IL-8可较好区分疾病严重程度,且对患者预后具有一定预测价值。     

病毒性肝炎患者血清IL-6和T细胞亚群的关系

采用ＭＴＴ比色法和抗体致敏的红细胞花环试验（间接法）　检测了９１例病毒性肝炎患者血清ＩＬ－６和Ｔ细胞亚群。　结果显示，病毒性肝炎患者血清ＩＬ－６活性均明显高于正常对照组（Ｐ＜０．０１），以重型肝炎为最高；且与肝细胞损害程度呈正比（Ｐ＜０．０１）；ＣＤ４~＋细胞、ＣＤ４＋／ＣＤ８~＋均明显降低，与血清ＩＬ－６呈负相关；ＣＯ８~＋细胞明显增高，与血清ＩＬ－６呈正相关（Ｐ＜０．０１）。表明，血清ＩＬ－６与机体细胞免疫功能密切相关，二者互为因果，共同参与病毒性肝炎的免疫病理损害，可作为判断病情和预后及免疫调节治疗的监测指标。     

Identification of α1-adrenoceptor subtypes in the dog prostate

Summary The ₁-adrenoceptor subtypes of dog prostate were characterized in binding and functional experiments. In saturation experiments, [³H]prazosin bound to ₁-adrenoceptors with high affinity. In the displacement experiments, unlabelled prazosin and WB4101 biphasically inhibited the binding of 400 pM [³H]prazosin, suggesting the presence of at least two distinct affinity sites for prazosin or WB4101. The proportion of high-affinity sites was approximately 10%. HV723 also recognized two distinct affinity sites but the proportion of high-affinity sites was approximately 20%. From these results the presence of three distinct ₁-adrenoceptor subtypes was suggested: presumably subtypes _1A (high affinity for prazosin and WB4101), _1N (high affinity for only HV723) and _1L (low affinity for the three antagonists) according to the recently proposed ₁-adrenoceptor subclassification. The density of subtype _1L was much higher than that of subtypes _1A and _1N subtypes. In the functional experiments, prazosin, WB4101 and HV723 competitively antagonized the contractile response to noradrenaline with low affinities close to those estimated for the _1L subtypes. These results suggest that the contractile response to noradrenaline in the dog prostate is mediated predominantly through _1L subtype -adrenoceptors.