Safety and efficacy of first-in-man intrathecal injection of human astrocytes (AstroRx®) in ALS patients: phase I/IIa clinical trial results.

Background: Malfunction of astrocytes is implicated as one of the pathological factors of ALS. Thus, intrathecal injection of healthy astrocytes in ALS can potentially compensate for the diseased astrocytes. AstroRx® is an allogeneic cell-based product, composed of healthy and functional human astrocytes derived from embryonic stem cells.

Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19.

An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is growing due to the most severe complications of the current coronavirus disease-2019 (COVID-19) pandemic. The human astrocytes (AstroRx) have shown immunomodulatory properties in the central nervous system (CNS).

Different dose regimens of 5-fluorouracil and interferon-alpha in patients with metastatic colorectal carcinoma.

Three different 5-fluorouracil (5-FU)-interferon-alpha-2b (IFN)-containing regimens were designed for treatment of patients with advanced colorectal cancer. 87 patients with a Karnofsky index > or = 70 were included in three sequential non-randomised phase II trials. Regimen A consisted of 5-FU (750 mg/m2/day) given as a continuous infusion on days 1-5 followed by weekly 1-h intravenous infusions until week 8.

Ontogeny of a human polychlorinated biphenyl-binding protein. Level of expression in tracheal aspirates in bronchopulmonary dysplasia.

A human lung polychlorinated biphenyl binding protein (PCB-BP,M(r) 13 kd) has recently been purified from lavage fluid. Polyclonal monospecific antibodies against PCB-BP were produced and used for immunohistochemical staining in sections of human lung tissue. PCB-BP was found to localize preferentially to the nonciliated (Clara) cells of the lung, whereas the alveolar cells and ciliated cells of the larger airways were devoid of staining.

Muscle protein synthesis after operation: effects of intravenous nutrition.

Objective: To assess the effect of an elective abdominal surgical operation (open cholecystectomy) on the rate of protein synthesis in skeletal muscle in humans.

Design: Prospective random control trial.

Setting: University hospital.

Mechanisms for differences in lipolysis between human subcutaneous and omental fat cells.

Catecholamine-regulation of lipolysis and beta-adrenoceptor binding isoterms were studied in human sc and omental isolated fat cells from 24 subjects undergoing elective cholecystectomy. The lipolytic sensitivity of the nonselective beta-agonists epinephrine and isoprenaline as well as the selective agonists norepinephrine (beta 1) and terbutaline (beta 2) was significantly increased 5-10 times in omental fat cells. On the other hand, no regional difference in antilipolytic sensitivity was seen for the alpha 2 agonist clonidine.

Free amino acids in plasma and muscle during 24 hours post-operatively--a descriptive study.

Intracellular amino acids in skeletal muscle show a specific concentration pattern on the third post-operative day. The temporal development of these changes has not been clarified. Here the amino acid concentrations in skeletal muscle were studied during the first post-operative day in fourteen patients undergoing elective abdominal surgery.

Quantitative comparison of insulin-like growth factor mRNA levels in human and rat tissues analysed by a solution hybridization assay.

In this study a solution hybridization assay was evaluated for its application to the measurement of levels of specific mRNAs. The evaluation included parameters such as incubation time, hybridization stringency and probe concentration/structure. Both short (50 bases derived from synthetic oligonucleotides) and long (125-147 bases) RNA probes, derived from cloned sequences, could be used to obtain quantitative information on specific mRNA species.

Glucocorticoid receptor mRNA expression in pulmonary alveolar macrophages in sarcoidosis.

The presence of the glucocorticoid receptor was demonstrated by immunocytochemistry in pulmonary alveolar macrophages obtained by bronchoalveolar lavage. Also, GR mRNA content was determined by solution hybridization in PAM from 12 healthy volunteers and in 6 patients with sarcoidosis. No significant differences with regard to GR mRNA expression was detected between the two groups examined.

Decreased insulin-stimulated 3-0-methylglucose transport in in vitro incubated muscle strips from type II diabetic subjects.

Peripheral insulin resistance in type II diabetes mellitus has been attributed to alterations in skeletal muscle glucose metabolism. However the direct dose-response relationship between insulin and glucose transport has not yet been studied in human skeletal muscle. We investigated 3-0-methylglucose transport in in vitro incubated skeletal muscle strips from eight healthy controls (age 61 +/- 6 yrs) and six lean type II diabetic patients treated with oral antidiabetic medication (age 73 +/- 3 yrs).

Metformin increases insulin-stimulated glucose transport in insulin-resistant human skeletal muscle.

The effect of metformin (0.1 mM) on glucose transport was investigated in healthy control and in insulin-resistant human skeletal muscle. Muscle samples (200-400 mg) were obtained from the rectus abdominis muscle (abdominal surgery) or from the vastus lateralis portion of the quadriceps femoris muscle (open biopsy technique) from 8 healthy controls (age 38 +/- 4 yrs, BMI 23 +/- 1) and from 6 insulin-resistant subjects (age 53 +/- 5 yrs, BMI 30 +/- 2).

Vasoactive intestinal peptide and secretin: effects of combined and separate intravenous infusions on bile secretion in man.

The effects of intravenously administered vasoactive intestinal peptide (VIP) and secretin on bile secretion were studied in 12 patients with complete biliary fistulas. The two peptides were administered both simultaneously and separately. During VIP infusion bile volume increased by 60%, and during the combined VIP and secretin infusion bile volume increased by another 70%.

Beta-adrenoreceptor subtype expression in human liver.

The pharmacological and gene expressions of beta 1- and beta 2-adrenoceptor subtypes (BAR1 and BAR2) were investigated in human liver by radioligand binding assays, adenylate cyclase experiments, and RNA excess solution hybridization. [125I]Cyanopinodolol, nonlabeled adrenergic agents, and BAR1/BAR2 cRNA were used as probes. The relationship between binding sites for BAR1 and BAR2 was markedly different from that between the basal mRNA expression for the two receptor subtypes.

Inhibition of lipolysis by agents acting via adenylate cyclase in fat cells from infants and adults.

The in vitro lipolytic effect of catecholamines is poor during infancy because of enhanced alpha 2-adrenoceptor activity. The mechanisms behind this were investigated in isolated fat cells obtained from 1- to 4-mo-old infants and from adults. The cells were incubated with agents that inhibit lipolysis through distinct receptors coupled to adenylate cyclase via the inhibitory GTP binding coupling protein, Gi.

Evidence that vasoactive intestinal peptide induces ductular secretion of bile in humans.

The effect of intravenously administered vasoactive intestinal polypeptide on bile secretion was studied in 11 patients with complete biliary drainage. After infusion of vasoactive intestinal polypeptide, bile volume increased by 65%. In the 2 patients investigated, the output of bicarbonate increased by approximately 250% and the concentration by 50%-70%.

Characterization of insulin resistance after surgery.

The effects of insulin on glucose utilization were investigated in seven nonobese patients before and 24 hours after elective cholecystectomy. Surgery was followed by a significant increase in the circulating levels of glucose and insulin. The hypoglycemic action of insulin was reduced by one third (p less than 0.

Changes in catecholamine-induced lipolysis in isolated human fat cells during the first year of life.

Catecholamine-induced lipolysis in isolated human adipocytes during the first year of life was investigated. During this period fat cell size increased markedly. Basal and catecholamine-induced glycerol release were positively correlated with age when lipolysis was expressed per cell.

Endoscopic fluorescein flowmetry in the evaluation of gastric and duodenal mucosal blood flow.

Fluorescein flowmetry (FF) implies the measurement of a relative capillary blood flow, expressed as an index--that is, the ratio between the maximum fluorescence, obtained during the first circulatory passage of sodium fluorescein (Na-F), and the rise time, defined as the time interval between 10% and 90% of the maximum fluorescence. The aim of this study was to develop FF to be used during endoscopy for the evaluation of ventricular and duodenal mucosal blood flow. FF was applied during gastroduodenoscopy in 38 patients with normal mucosa, as verified by histopathologic examination.

The transcapillary exchange of sodium fluorescein in ischaemic limbs measured by fluorescein flowmetry.

The transcapillary exchange of sodium fluorescein in the skin of 36 extremities (19 patients) with arterial occlusive disease was measured using two different ways of analysing the tissue fluorescence, fluorescein flowmetry (FF) and dynamic fluorescein angiography (FA). 7 mg sodium fluorescein/kg body weight was given intravenously. With FF, the transcapillary exchange of sodium fluorescein is expressed in arbitrary units as a fluorescence index.

Role of alpha-adrenoceptors for adipocyte size in man.

Catecholamines have dual effects on lipid mobilization in man. Lipolysis is stimulated via beta-adrenoceptors and inhibited via alpha 2-adrenoceptors. The relationship between fat-cell size and catecholamine-induced lipolysis (expressed per cell surface area) was investigated in vitro in subcutaneous adipocytes of thirty-five non-obese subjects between 1 month and 45 years of age.

Nonresectable malignant bile duct obstruction. Surgical bypass or endoprosthesis?

Forty-one patients with malignant obstructive jaundice, not amenable to radical surgery, had biliary decompression by either surgical bypass or endoscopically introduced endoprosthesis. The two treatment groups were statistically comparable with reservation for age, which was significantly lower in the operated group. Judged by the effect on bilirubin and alkaline phosphatase levels the two methods were equally efficient.

Peritoneovenous shunts for malignant ascites.

The intractable malignant ascites of 27 patients was treated by insertion of a peritoneovenous shunt. Eight had a Le Veen shunt, 17 a Denver shunt, one patient had a Denver shunt subsequently replaced by a Le Veen shunt and one a Denver shunt which was replaced by another Denver shunt. The operations were safely performed under local anesthesia.

Angiodysplasia of the colon requiring emergency surgery.

Three patients with massive bleeding from colonic angiodysplasia, all requiring emergency surgery, are presented. Prior to operation, the bleeding source was localized by angiography and colonoscopy. By this means the resection could be limited to the right colon.

Emergency oesophageal transection for uncontrolled variceal bleeding.

Nine patients with bleeding oesophageal varices, who had not responded to aggressive conservative treatment, underwent emergency transabdominal oesophageal transection and reanastomosis using a mechanical stapling instrument. According to the classification of Child, 2 were graded as Class A, 4 as Class B, and 3 as Class C. Successful control of haemorrhage was achieved in all patients.

Metastatic breast carcinoma causing intestinal obstruction.

Two cases of metastasis from breast carcinoma to the small intestine are discussed. The literature is reviewed and the macroscopic view of the tumours is discussed.