Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Chyle leak following biliary pancreatitis.

Chylous ascites is a rare clinical entity that historically has been accompanied by high mortality due to the association with malignancy. Here we present a case of chylous ascites as a complication of mild pancreatitis in a young woman. We review the literature of similar cases, which revealed four similar cases with a range of outcomes. Treatment options vary from dietary restriction of medium chain fatty acids, total parental nutrition, radiological intervention and surgery.

Does sodium bicarbonate reduce painful voiding after flexible cystoscopy? A prospective, randomized, double-blind, controlled trial.

OBJECTIVE: • To determine if sodium bicarbonate (Ural) reduces painful voiding after flexible cystoscopy. PATIENTS AND METHODS: • 300 patients over 18 years old undergoing elective flexible cystoscopy were enrolled in a randomized, double-blinded, placebo-controlled trial. Patients with active urinary tract infections, indwelling urinary catheters and/or requiring additional procedures such as biopsy and dilatation were excluded. • Painful voiding was quantified using a pain analogue scale from 0 to 10. Pre-existing painful voiding, previous experience with Ural and flexible cystoscopy were recorded. • Flexible cystoscopy was performed to a standard protocol. Patients were randomised after recruitment to receive Ural or placebo (glucose) powder four times a day for two days after the procedure. Trial outcome was assessed by estimating the change in pain incidence and severity from before to two days after by post-procedural questionnaire. RESULTS: • Painful voiding was present in 84 of the 300 patients post flexible cystoscopy (45 of 160 patients receiving Ural; 39 of 140 receiving placebo), but overall mean pain scores were low (1.25; standard deviation 2.4; on a 0-10 scale). • Treatment with Ural compared to placebo was associated with a non-significant reduction in frequency of pain (28.9% vs 31.3%; incidence rate ratio 0.66; 95% CI 0.29-1.46; P = 0.30) and severity of pain (odds ratio 0.72; 95% CI 0.30-1.74; P = 0.47). CONCLUSION: •In the replicable context of low post-cystoscopy pain levels, we believe Ural does not reduce painful voiding after flexible cystoscopy.

Hirschsprung's disease: a regional experience.

BACKGROUND: Hirschsprung's disease (HD) is widely quoted to have an incidence of approximately 1 in 5000 live births. However, it is also known that regional variation in incidence can occur. The aim of this paper was to study the incidence of Hirschsprung's disease in Tasmania and to document a regional experience of HD. METHODS: A retrospective review of all patients with newly diagnosed HD between January 1998 and December 2005 was carried out. Data were extracted from medical records and reported. Tasmanian birth statistics from 1998 to 2005 were obtained from the Australian Bureau of Statistics website and the incidence was calculated. RESULTS: Over the 8-year study period, 14 new cases of HD were identified in Tasmania. The estimated incidence of HD in Tasmania based on this study is 1 in 3429. This incidence is higher than the widely quoted incidence of 1 in 5000, but the difference did not reach statistical significance. Between 2003 and 2005, there was a surge in the number of cases with 11 of 14 cases being derived from these 3 years. No obvious reasons were found to explain this surge in the number of cases. Abdominal distension and vomiting were most common modes of presentation (100 and 71%, respectively). There was delayed passage of meconium in 43%. CONCLUSION: The incidence of Hirschsprung's disease seems higher in Tasmania. The surge in the number of cases is also of interest, although the reasons behind this remain unknown. Delayed passage of meconium was also less common than previously cited.

Deuterium NMR spectroscopy of biosynthetically deuterated mammalian tissues.

The choline-containing phospholipids of mammalian membranes have been biosynthetically deuterated by raising rats on a diet supplemented with [HOCH2CH2N(CD3)3]+Cl- or [HOCD2CH2N(CH3)3]+Cl-. Deuterium NMR spectra have been obtained from excised deuterated brain, sciatic nerve, heart, and lung, from isolated brain myelin and brain microsomes, and from aqueous dispersions of lipid extracts. Measurements of residual quadrupole splittings for excised deuterated neural tissues demonstrate that the orientational order of the choline head group is similar to that observed in model membranes. The spin-lattice relaxation time of the choline head group in deuterated neural tissue is indistinguishable from that observed in model membranes. These results support the proposal that the conformation and motional dynamics of the choline head groups of the bulk choline-containing lipids of neural tissue are similar to those in model membranes. Spectra of biosynthetically deuterated brain myelin and brain microsomes exhibit similar quadrupole splittings. Since these membranes have significantly different protein contents, these results indicate that no strong polar interactions exist between membrane proteins and the choline head groups of choline-containing membrane lipids. Spectra of intact deuterated heart and lung exhibit broad lines and a range of quadrupole splittings. Due to the heterogeneous nature of these tissues, interpretation is difficult. However, no strong ordering of the lipid head group by protein is indicated.

Pharmacokinetics and metabolic fate of two nitroxides potentially useful as contrast agents for magnetic resonance imaging.

Paramagnetic nitroxyl-containing compounds have been useful as contrast agents in magnetic resonance imaging (MRI) experiments in animals. Preliminary information on the metabolic fate, pharmacokinetic behavior, stability in tissues, and chemical reduction of two prototypic nitroxides, PCA and TES, is presented. In the dog TES was eliminated more rapidly than PCA. More than 80 % of the dose of both nitroxides was recovered in urine within 6 hours. Nitroxides were reduced in vivo to their corresponding hydroxylamines. No other metabolite was observed. Measured reducing activity in tissue homogenates was greater in liver or kidney than in brain, lung or heart. In each tissue PCA was more stable than TES. PCA was also more resistant to reduction by ascorbic acid at physiologic pH. These preliminary results favor the use of PCA, a pyrrolidinyl nitroxide, over TES, a piperidinyl nitroxide, for MRI contrast enhancement.

Brain nuclear magnetic resonance imaging enhanced by a paramagnetic nitroxide contrast agent: preliminary report.

Contrast-enhancing agents for demonstrating abnormalities of the blood-brain barrier may extend the diagnostic utility of proton nuclear magnetic resonance (NMR) imaging. "TES," a nitroxide stable free radical derivative, was tested as a central nervous system contrast enhancer in dogs with experimentally induced unilateral cerebritis or radiation cerebral damage. After intravenous injection of TES, the normal brain showed no change in NMR appearance, but areas of disease demonstrated a dramatic increase (up to 45%) in spin-echo intensity and a decrease in T1 relaxation times. The areas of disease defined by TES enhancement were either not evident on the nonenhanced NMR images or were better defined after contrast administration. In-depth tests of toxicity, stability, and metabolism of this promising NMR contrast agent are now in progress.

Work in progress: nuclear magnetic resonance study of a paramagnetic nitroxide contrast agent for enhancement of renal structures in experimental animals.

A piperidinyl nitroxide stable free radical derivative, TES, was tested as an NMR contrast enhancer of renal structures in normal animals and animals with experimentally induced unilateral renal ischemia, renal vascular congestion, and hydronephrosis. Physiologic measurements indicated that TES is rapidly excreted in the urine with a clearance rate equal to the glomerular filtration rate. Because the compound is strongly paramagnetic, it increases the observable NMR intensity within the kidneys and urine in relatively low doses (0.04 to 0.9 g/kg). TES-enhanced spin echo renal images clearly demonstrated the presence of disease and functional abnormalities in diseased kidneys. These abnormalities were either not evident or only indirectly suggested on nonenhanced NMR images.