Induction of transient hyperglycaemia in cancer patients

Serum glucose levels up to 700 mg/dl were achieved and maintained for 3 h in patients with advanced metastatic cancer by infusion of concentrated glucose solutions. Even with infusions of large amounts of glucose, the maximum sustainable level of serum glucose did not exceed 700 mg/dl. The apparent ceiling of serum glucose level appeared to be due to a large and rapid loss of glucose from the kidneys. With adequate fluid volume replacement there was no rebound hypoglycaemia and there was no significant changes in haematocrit or electrolytes.     

Water content in human intervertebral discs. Part I. Measurement by magnetic resonance imaging

Tension-relaxation experiments were performed on human disc lamellae specimens. The water content was found to affect the viscoelastic behavior and a master relaxation curve was constructed from the experimental data. The water content of disc phantoms is measured by magnetic resonance imaging (MRI) techniques. MRI was used to compare the discs of patients of different ages. The possibility of obtaining cross-sectional water distribution in human intervertebral disc material using MRI techniques and its relation to the disc's mechanical properties was explored, with the goal of constructing a realistic mathematical model of the disc which takes into account the water content of the disc.     

Results of resection and proposed guidelines for patient selection in instances of non-colorectal hepatic metastases

Resection of hepatic metastases from carcinomas of the colon and rectum appears to extend the survival time in appropriately selected patients. Selection criteria have been widely published. Similar data for patients with hepatic metastases from primary sites other than the colon and rectum are lacking. To determine which, if any, patients in the latter category benefit from resections, we reviewed ten such instances treated at our institution plus 141 instances of resection for noncolorectal hepatic metastases previously reported. The over-all five year survival rate after resection of noncolorectal hepatic metastases is 20 per cent. When Wilms' tumor is excluded, the five year survival rate is 15 per cent. Approximately four of ten patients with metastases to the liver from Wilms' tumor or carcinoid survived five years after resection. Similar benefit is rarely obtained after resection of hepatic metastases of the breast, kidney, adrenal gland and carcinomas of the stomach; malignant melanoma, and leiomyosarcoma. No extension of survival is apparent for resection of hepatic metastases of gynecologic malignancies or carcinoma of the pancreas. Specific guidelines for selection are discussed in view of the limited prognosis when tumors other than carcinomas of the colon and rectum metastasize to the liver. Careful patient selection and minimization of complications are required.     

Mutant of Chinese hamster ovary cells with altered mannose 6-phosphate receptor activity is unable to synthesize mannosylphosphoryldolichol.

B4-2-1 is a Chinese hamster ovary cell mutant previously isolated and characterized as deficient in mannose 6-phosphate receptor activity. We show here that B4-2-1 is a pleiotropic mutant, defective in biosynthesis of asparagine-linked oligosaccharides, B4-2-1 is unable to synthesize mannosylphosphoryldolichol; the consequences of this defect on glycosylation are (i) biosynthesis of one major lipid-linked oligosaccharide, characterized by its resistance to endoglycosidase H and decreased size; this oligosaccharide is similar to a minor species of lipid-liked oligosaccharide found in parental cells; (ii) transfer of this oligosaccharide to newly synthesized proteins; and (iii) absence of normal "high-mannose" oligosaccharides on mature glycoproteins isolated from B4-2-1; glycoproteins from the mutant contain complex oligosaccharides as well as endoglycosidase H-resistant, alpha-mannosidase-sensitive species. While the glycosylation defect may alter adversely the function of several glycoproteins in the mutant, including that of the mannose 6-phosphate receptor, it appears to have no effect on the formation or function of the mannose 6-phosphate recognition marker on acid hydrolases of B4-2-1.     

Multiple antibodies targeting tumor-specific mutations redirect immune cells to inhibit tumor growth and increase survival in experimental animal models

T cell therapy for cancer involves genetic introduction of a target-binding feature into autologous T cells, ex vivo expansion and single large bolus admin     

Clinical pharmacology of imeglimin for the treatment of type 2 diabetes

ABSTRACT

Introduction

With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.     

Use of prokinetic agents in hospitalised adult patients: A scoping review

Background

Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinetic agents in hospitalised patients. We hypothesised, that the body of evidence would be limited and derive from heterogeneous populations.

Methods

We conducted this scoping review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews statement. We searched Medline, Embase, Epistemonikos and the Cochrane Library for studies assessing the use of prokinetic agents on any indication and outcome in adult hospitalised patients. We used a modified version of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to assess the certainty of evidence.

Results

We included 102 studies with a total of 8830 patients. Eighty-six studies were clinical trials (84%), and 52 (60%) of these were conducted in the intensive care unit, with feeding intolerance as the main indication. In the non-intensive care setting the indications were wider; most studies assessed use of prokinetic agents before gastroscopy to improve visualisation. The most studied prokinetic agent was metoclopramide (49% of studies) followed by erythromycin (31%). In total 147 outcomes were assessed with only 67% of the included studies assessing patient-centred outcomes, and with gastric emptying as the most frequently reported outcome. Overall, the data provided no firm evidence on the balance between the desirable and undesirable effects of prokinetic agents.

Conclusions

In this scoping review, we found that the studies addressing prokinetic agents in hospitalised adults had considerable variations in indications, drugs and outcomes assessed, and that the certainty of evidence was judged to be low to very low.