Autoradiographic localization of kappa opiate receptors in CNS taste and feeding areas

Recent evidence suggests that kappa opiate receptors may play a key role in the regulation of appetite. Such evidence implies that kappa receptors might be localized within specific brain areas known to regulate ingestive behaviors. On the basis of this implication we employed an in vitro film autoradiographic technique using 3H-ethylketocyclazozine as ligand to identify putative kappa receptors within CNS "taste" nuclei and surrounding areas. Coronal cryostat sections of rat brain were incubated with ligand in the presence of D-Ala2, D-Leu5-enkephalin (DADLE) and morphine, apposed to LKB Ultrofilm for 60 days, processed and kappa receptor densities evaluated with the aid of a hand held photometer and video image analyzer. Highest kappa receptor densities were found within various gustatory and feeding sites including the rostral pole of the nucleus of the solitary tract, parabrachial nuclei, ventral posterior and medial portions of the thalamus, medial hypothalamus, medial nuclei of the amygdala and bed nucleus of the stria terminalis. Various other midline and medial limbic areas also showed significant kappa densities.     

Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II).

Primary genetic factors are etiologic in at least 5-10% of patients with colon cancer. The polyposis syndromes (FPC) are easily identified examples because of the spectacular number of polyps. The hereditary nonpolyposis syndromes (HNPCC), although five times more common than FPC, are usually not recognized because they do not have such a distinctive clinical, premonitory genetic marker. Colorectal cancer expression was surveyed in 10 extended, thoroughly documented HNPCC kindreds. One hundred sixteen patients were found to have 183 colorectal cancers. Despite the striking family history, less than 5% were correctly treated by subtotal colectomy. This provided a unique opportunity to study the natural history. Five findings differed significantly (p less than 0.05) from patients with sporadic colon cancer: (1) mean age of initial colon cancer diagnosed was 45.6 years; (2) 69.1% of first colon cancers were located proximal to the splenic flexure of the colon; (3) 18.1% had synchronous colon cancer; (4) 24.2% had metachronous colon cancer develop with life table analysis showing the risk for a metachronous lesion at 10 years to be 40%; and (5) only 23.3% of cancers were located in the sigmoid colon or rectum. Based on this data, it is recommended that the family history of all patients with a newly diagnosed colon cancer be evaluated for evidence of this syndrome. If an autosomal dominant inheritance pattern emerges, an in-depth genetic investigation is indicated. When HNPCC is confirmed, the following recommendations apply: a subtotal abdominal colectomy is indicated at the time of the initial colon cancer because of the risk of synchronous and metachronous lesions. The rectum should be spared in favor of careful lifetime surveillance because of the proclivity for proximal colon cancer involvement. As yet unaffected members of a newly diagnosed HNPCC kindred who are in the "direct genetic line" should be cautioned that they are at 50% risk and must begin an intensive surveillance program beginning in the third decade with careful attention to the right colon. Patients from newly diagnosed HNPCC families who have had a previous conventional colectomy for colon cancer should, at the very least, enter an intensive surveillance program; a prophylactic completion subtotal colectomy should be considered for patients who are less than totally compliant.     

Comparison of renal function after open radical cystectomy,extracorporeal robot assisted radical cystectomy,and intracorporeal robot assisted radical cystectomy

PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m². Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m². Renal function decline was defined as a ≥10 ml/min/1.73m² drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m², P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.     

Kidney transplant program waitlisting rate as a metric to assess transplant access

Kidney transplant program performance in the United States is commonly measured by posttransplant outcomes. Inclusion of pretransplant measures could provide a more comprehensive assessment of transplant program performance and necessary information for patient decision-making. In this study, we propose a new metric, the waitlisting rate, defined as the ratio of patients who are waitlisted in a center relative to the person-years referred for evaluation to a program. Furthermore, we standardize the waitlisting rate relative to the state average in Georgia, North Carolina, and South Carolina. The new metric was used as a proof-of-concept to assess transplant-program access compared to the existing transplant rate metric. The study cohorts were defined by linking 2017 United States Renal Data System (USRDS) data with transplant-program referral data from the Southeastern United States between January 1, 2012 and December 31, 2016. Waitlisting rate varied across the 9 Southeastern transplant programs, ranging from 10 to 22 events per 100 patient-years, whereas the program-specific waitlisting rate ratio ranged between 0.76 and 1.33. Program-specific waitlisting rate ratio was uncorrelated with the transplant rate ratio (r = −.15, 95% CI, −0.83 to 0.57). Findings warrant collection of national data on early transplant steps, such as referral, for a more comprehensive assessment of transplant program performance and pretransplant access.     

Public discourse and policy change: Absence of harm from increased oversight and transparency in OPO performance

The Centers for Medicare and Medicaid Services announced changes to the Final Rule for organ procurement organizations (OPOs) in November 2020, after a 23-month period of public debate. One concern among transplant stakeholders was that public focus on OPO underperformance would harm deceased donation. Using CDC-WONDER data, we studied whether donation performance dropped during the era of public debate about OPO reform (December 2018–February 2020). Overall OPO performance as measured relative to cause, age, and location-consistent deaths rose by 12.3% in 2019, compared to a median annual change of 2.5% 2009–2019. Organ recoveries exceeded seasonally adjusted forecasts by 4.2% in the first half of 2019, by 8.1% following the Executive Order issuing a mandate for OPO metric reform, and by 14.1% between the Notice of Public Rule Making and the onset of COVID-19-related systemic disruptions. We describe changes in donor phenotype in the period of increased performance; improvement was greatest for older and donation after cardiac death (DCD) donors, and among decedents who did not have a drug-related mechanism of death. In summary, performance during an era of intense public debate and proposed regulatory changes yielded 692 additional donors over expectations, and no detriment to organ donation was observed.     

肢端型系统性硬皮病误诊1例

1　病例报告　女 ,45岁 ,因吞咽困难 16 mo伴发热 15 d,于1999- 0 7- 12入院 .于 16 mo前与人争吵后出现吞咽困难 ,以进食馒头、面条为著 ,剑突下有时出现梗噎感 ,随即呕吐 ,呕出所进食物及粘液 ,情绪波动可诱发症状加重 ,伴食欲减退、返酸 .15 d前无诱因出现不规则发热 ,T38～ 39℃ ,上腹痛加重 ,全身酸困不适 ,乏力、头晕、消瘦 .追问病史 ,患者 5 a前双手、足疼痛麻木 ,尤以受凉、精神刺激后明显 ,手指初发白 ,继而发紫 ,变红 ,且麻木疼痛加重 ,手足小关节渐僵硬、畸形 .曾到多家医院就诊 ,诊断 :“雷诺病、类风湿性关节炎”.2 a前出现…     

Triplications of chromosome 1p36.3, including the genes GABRD and SKI,are associated with a developmental disorder and a facial gestalt

Triplication of chromosomal region 1p36.3 is a rare genomic rearrangement. In this report, we delineate the phenotypic spectrum associated with 1p36.3 triplications. We describe four patients with microtriplications of variable size, but with a strong phenotypic overlap, and compare them to previously described patients with an isolated triplication or duplication of this region. The 1p36.3 triplication syndrome is associated with a distinct phenotype, characterized by global developmental delay, moderate intellectual disability, seizures, behavioral problems, and specific facial dysmorphic features, including ptosis, hypertelorism, and arched eyebrows. The de novo occurrence of these microtriplications demonstrates the reduced reproductive fitness associated with this genotype, in contrast to 1p36.3 duplications which are mostly inherited and can be associated with similar facial features but with a less severe developmental phenotype. The shared triplicated region encompasses four disease-related genes of which GABRD and SKI are most likely to contribute to the phenotype.     

The Low-Grade Lymphomas

The lymphomas comprise a spectrum of diseases with vast variation in histologic appearance, presentation and natural history, and response to therapy. At one end of the spectrum are the low-grade lymphomas (LGLs), indolent malignancies characterized by paradox. Despite an exceedingly low growth fraction, the LGLs are usually extensive at presentation, and yet they rarely involve privileged sites, such as cortical bone or central nervous system, and rarely destroy adjacent tissue. They are exquisitely responsive to many different therapeutic interventions, but responses to most agents are transient and similar. Finally, although survival of most LGL patients is measured in years, the course of the disease is punctuated by both transient and long-term responses to treatment, and also by spontaneous regression and transformation to more aggressive lymphomas in the absence of therapy, rendering the evaluation of the true impact of treatment quite difficult. The focus of this review is on the management of the LGLs, in particular the role of radiotherapy.