Effects of Insulin-like Growth Factor-I and its Analogue,Long-R 3 -IGF-I,on Intestinal Absorption of 3- O -methyl- d -glucose are Less Pronounced than Gut Mucosal Growth Responses

The relationship between insulin-like growth factor-I (IGF-I) peptide-induced increases in bowel mass and functional improvement is unclear. We utilised three independent methods to investigate the effects of IGF-I peptides on intestinal absorption of the glucose analogue, 3- O -methyl- d -glucose (3MG) in rats. Rats received vehicle, IGF-I or the more potent analogue, long-R 3 -IGF-I via subcutaneously implanted mini-pump, for 7 days, at which time intestinal absorption was assessed by: (1) plasma 3MG appearance following oral gavage, (2) single-pass- or (3) recirculating-perfusion of a jejunal segment. 3MG (320 or 800 &#117 mg) was gavaged on day 7 to rats treated with vehicle, IGR-I or long-R 3 -IGF-I. With the lower 3MG dose, only long-R 3 -IGF-I increased (40%) the initial rate of 3MG appearance in plasma. IGF-I had no significant effect, whilst at the higher 3MG dose neither peptide was effective. Utilising perfusion techniques, long-R 3 -IGF-I, but not IGF-I, significantly increased 3MG uptake per cm of jejunum by up to 69%, although significance was lost when expressed as a function of tissue weight. Long-R 3 -IGF-I, but not native IGF-I, enhanced 3MG absorption from the intestinal lumen, presumably reflecting an increased mucosal mass rather than an up-regulation of specific epithelial glucose transporters.     

Musculoskeletal pain in older adults at the end-of-life: a systematic search and critical review of the literature with priorities for future research

Background

Pain is an important issue in end of life care. Although musculoskeletal pain is common in older adults, it is rarely associated with the cause of death and may be overlooked as death approaches. Hence a major target for improving quality of life may be being missed.

Methods

The aim of this study was to systematically search and critically review the literature on musculoskeletal pain at the end of life. Amed, Cinahl, Internurse, Medline, Psych Info, Web of Knowledge and Cochrane review databases were searched for relevant research up to September 2012. The search strategy combined key words expanding the terms ‘palliative’ for population, ‘musculoskeletal’ for exposure, and ‘pain’ for outcome. Predefined inclusion and exclusion criteria were applied.

Results

Five relevant papers and one letter to the editor were found, including case studies and epidemiological research. Current evidence suggests musculoskeletal pain is common in older adults at the end of life and that it can have a substantial impact on individual experience. No information about community based treatment of musculoskeletal pain at the end of life was found.

Conclusion

Priorities for future research include high quality epidemiological studies to establish the prevalence, natural history, impact, assessment, patient priorities and outcomes associated with musculoskeletal pain in the end of life period, and intervention research that provides an evidence base for treatment.

     

Interferon gamma release assay in the diagnosis of tuberculous mastitis

Tuberculous mastitis is rare, especially in Western countries. We describe a case where the interferon gamma release assay blood test led to diagnosis and successful treatment of the disease.     

Regulation of erythropoietin production in a human hepatoblastoma cell line

Production of immuno and biologically active erythropoietin was documented to occur in the human hepatoblastoma cell line HepG-2. The expression of the erythropoietin gene was further verified by Northern blot analysis using a single stranded RNA probe. In vitro studies showed that erythropoietin production by these cells was not stimulated by hypoxia or cobalt chloride, but was related to the proliferative activity of the cells in culture. In addition it was found that the secretion of erythropoietin was almost completely abrogated by tunicamycin, an inhibitor of N-linked glycosylation. This effect of tunicamycin was also observed in a permanently transfected cell line that secretes erythropoietin in large quantities.     

Effect of stool size and consistency on defecation.

The ability of subjects to expel from the rectum objects simulating stools of different characteristics was assessed in paired studies carried out in a total of 58 normal subjects and 25 young women with severe constipation. Our results showed that a lower percentage of normal subjects and a lower percentage of constipated patients were able to pass a 1.8 cm incompressible sphere compared with a 50 ml deformable balloon, although constipated patients found it more difficult than normal subjects to expel both types of simulated stool. It was also more difficult for normal subjects to pass a soft compressible silicon rubber simulated stool than a stool made up of a similar volume of incompressible 1 cm wooden spheres contained in a cylindrical latex envelope, but both objects were much easier to pass than the same number of 1 cm spheres placed loose within the rectum. When normal subjects were instructed to expel single incompressible spheres of different sizes placed in the rectal ampulla, the intrarectal pressure and the time needed to pass these objects varied inversely with their diameter. These results suggest that more effort is required to expel stools from the rectum if they are small and hard than if they are large and soft.     

Adaptation of hydrogen analysis to measure stomach to caecum transit time in the rat

Excreted hydrogen analysis was used to measure stomach to caecum transit time of the head of a test meal in 120 rats fed by gavage. Results were compared with the distribution of a labelled test meal in the gastrointestinal tract of rats killed at different time intervals after gavage. Values for stomach to caecum transit were compatible with the distribution of labelled meals in 91% of animals, although in the remainder the hydrogen concentration had not risen even though food residues were in the caecum when the animals were killed. The technique gave reproducible results; the coefficients of variation for four studies carried out in each of six animals varied between 4 and 14%. A meal consisting of homogenised baked beans had a significantly shorter stomach to caecum transit time (88.1 +/- 4.5 min; mean +/- SE; n = 21; p less than 0.001) than an equivalent volume of Complan/lactulose (180.9 +/- 8.7 min; n = 13). This technique was used to investigate the effect of ileal infusion of a fat emulsion (20% Intralipid) via a chronically implanted intestinal cannula on the stomach to caecum transit time of a bean meal, in a series of paired studies carried out in six rats. Stomach to caecum transit time was significantly delayed during ileal infusion of 20% Intralipid compared with the control infusion of an isotonic saline solution (218.3 +/- 21 min v 106.7 +/- 33 min Intralipid v saline; n = 6; p less than 0.001).     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

Use of anorectal manometry during rectal infusion of saline to investigate sphincter function in incontinent patients

Anal and rectal pressures and external sphincter electromyogram were recorded continuously during rectal infusion of 1.5 L saline in 18 normal subjects and 37 patients who complained of diarrhea and fecal incontinence. All subjects exhibited a pattern of regular fluctuations in anorectal pressure and electromyogram. All except 1 of the normal subjects were able to retain 1500 ml saline without leakage, and their pressure record comprised simultaneous rectal contractions, internal sphincter relaxations, and external sphincter contractions. None of the incontinent patients were able to retain 1500 ml saline without leakages, and leakages always coincided with the peaks of rectal pressure. Two manometric patterns were observed. Fifty-nine percent of incontinent patients exhibited a pattern of contractions of similar profile occurring throughout the anorectum. This finding was associated with low basal sphincter pressures, an easily inhibited anal sphincter tone, an obtuse anorectal angle, and a funnel-shaped configuration to the anal canal. These results suggested that, in this group, the internal sphincter was weak and easily inhibited so that the whole anorectum behaved as one fluid-filled compartment recording contractions of the external sphincter. The remaining 41% of incontinent patients exhibited a normal pattern of anorectal pressure fluctuations and had normal maximum basal pressures, although maximum squeeze pressures, rectoanal inhibitory reflex, and anorectal angles were abnormal. Peak rectal pressures were abnormally high in this group during saline infusion, suggesting that abnormally strong rectal contractions may play a role in the incontinence in this group.     

Sentinel-Lymph-Node-Mapping beim Adenokarzinom des Kolons verbessert nicht die Genauigkeit des Tumorstagings

ZusammenfassungZiel: In dieser Studie sollten die Wirksamkeit von Sentinel-Lymph-Node-Mapping bei Patienten mit intraperitonealem Kolonkarzinom bestimmt und ein Algorithmus zur Vorhersage eines möglichen Überlebensvorteils unter Verwendung Sentinel-Node-Mapping und Lymphknoten-Ultrauntersuchungstechniken favorisierender Best-Case-Einschätzungen entwickelt werden.Methodik: 41 Patienten mit intraperitonealem Kolonkarzinom, die sich einer Kolektomie mit kurativer Zielsetzung unterzogen, wurden prospektiv untersucht. Nach Mobilisation von Kolon und Mesenterium wurden 1–2 ml des Farbstoffs Isosulfanblau subserös um den Tumor herum injiziert. Die ersten blaugefärbten Lymphknoten wurden als Sentinel Nodes (Wächterknoten) identifiziert. Weitere Knoten wurden vom Pathologen routinemäßig durch manuelle Präparation des Mesenteriums erkannt. Alle Knoten wurden routinemäßig durch histologische Untersuchung mittels Hämatoxylin-Eosin-Färbung aufgearbeitet. Um einen Algorithmus zur Vorhersage des möglichen Überlebensvorteils durch Sentinel-Node-Mapping und Lymphknoten-Ultrauntersuchungstechniken zu entwickeln, wurden Annahmen auf der Basis von Literaturdaten postuliert. Jede Tendenz war auf den Erfolg der Techniken gerichtet.Ergebnisse: Drei von 41 Patienten (7%) wurde keine Farbe injiziert, und sie wurden von der weiteren Analyse ausgeschlossen. Das Krankheitsstadium der übrigen 38 Patienten verteilte sich wie folgt: Stadium I: n = 10 (26%); Stadium II: n = 15 (39%); Stadium III: n = 11 (29%); Stadium IV: n = 2 (5%). Mindestens ein Sentinel Node wurde bei 30 von 38 Patienten (79%) identifiziert. Die mittlere Anzahl erkannter Wächterknoten lag bei zwei (Streuung ein bis drei). Die mittlere insgesamt gewonnene Anzahl an Lymphknoten betrug 14 (Streuung sieben bis 45). Bei 26 von 38 Patienten (68%) waren alle Knoten negativ. Sentinel Nodes und Nonsentinel Nodes waren bei zwei von 38 Patienten (5%) positiv. Bei einem von 38 Patienten (3%) waren Sentinel Nodes die einzigen positiven Lymphknoten. Bei neun von 38 Patienten (24%) waren Sentinel Nodes negativ und Nonsentinel Nodes positiv. Folglich wäre Sentinel-Node-Mapping nur für 3% möglicherweise von Nutzen gewesen, versagte aber in 24% der Patienten unserer Untersuchung bei der genauen Erkennung von Lymphknotenmetastasen. Um einen Algorithmus zur Berechnung des Überlebensvorteils zu entwickeln, trafen wir folgende Annahmen: Kombination des Krankheitsstadiums I und II (0,5); Anteil des Materials, bei dem durch Anwendung histologischer Untersuchung mittels Hämatoxylin-Eosin-Färbung das Stadium zu niedrig eingestuft worden war und das bei differenzierterer Analyse verborgene positive Knoten enthalten könnte (0,15); Anteil von okkulten positiven Knoten, die durch Sentinel-Node-Mapping entdeckt wurden (0,9); sowie Überlebensvorteil durch Chemotherapie (0,33). Somit läge der Anteil der Patienten, die von Sentinel-Lymph-Node-Mapping und Lymphknoten-Ultrauntersuchungstechniken profitierten, bei 0,02 (2%).Schlussfolgerungen: Sentinel-Node-Mapping mit Isosulfanblau-Färbung und Routineaufarbeitung entnommener Knoten verbessert die Genauigkeit des Stagings bei Patienten mit intraperitonealem Kolonkarzinom nicht. Sogar bei Anwendung von Best-Case-Annahmen ist der Prozentsatz von Patienten, die möglicherweise vom Sentinel-Lymph-Node-Mapping profitieren könnten, klein.Übersetzter Nachdruck aus Diseases of the Colon & Rectum 2005;48:80–5. DOI 10.1007/s10350-0795-5     

Influence of acid-pepsin secretion on gastric emptying of solids in humans: studies with cimetidine.

The commonly accepted model for gastric emptying suggests that the 'antral mill' is responsible for the triturition and subsequent emptying of solid food from the stomach. Little is known about the contribution to solid emptying made by other digestive mechanisms such as acid-pepsin secretion. We have investigated the effect of inhibiting gastic secretion on the rate at which a solid test meal emptied from the stomach. Using a radiolabelled beefburger, we performed paired gammacamera studies on consecutive days in 10 fasted, healthy volunteers to compare gastric emptying of the test meal with and without oral cimetidine (400 mg 1 hour before the test, 800 mg at the start of the meal). Inhibition of acid-pepsin secretion by cimetidine was associated with an appreciable delay in the rate of emptying of the burger from the stomach (T50 cimetidine 187 (16) min (mean (SEM); T50 no cimetidine 146 (15) min; p less than 0.01, paired t test). This delay was related to a change in the slope of the emptying profile and was not associated with a prolonged lag phase. These results may be explained by the relative achlorhydria and reduced pepsin activity induced by cimetidine impairing the breakdown of solid food into particles small enough to leave the stomach.