Effect of oral nutritional supplementation on wound healing in diabetic foot ulcers: a prospective randomized controlled trial.

AIMS: Among people with diabetes, 10-25% will experience a foot ulcer. Research has shown that supplementation with arginine, glutamine and ß-hydroxy-ß-methylbutyrate may improve wound repair. This study tested whether such supplementation would improve healing of foot ulcers in persons with diabetes. METHODS: Along with standard of care, 270 subjects received, in a double-blinded fashion, (twice per day) either arginine, glutamine and ß-hydroxy-ß-methylbutyrate or a control drink for 16 weeks. The proportion of subjects with total wound closure and time to complete healing was assessed. In a post-hoc analysis, the interaction of serum albumin or limb perfusion, as measured by ankle-brachial index, and supplementation on healing was investigated. RESULTS: Overall, there were no group differences in wound closure or time to wound healing at week 16. However, in subjects with an albumin level of ≤ 40 g/l and/or an ankle-brachial index of < 1.0, a significantly greater proportion of subjects in the arginine, glutamine and ß-hydroxy-ß-methylbutyrate group healed at week 16 compared with control subjects (P = 0.03 and 0.008, respectively). Those with low albumin or decreased limb perfusion in the supplementation group were 1.70 (95% CI 1.04-2.79) and 1.66 (95% CI 1.15-2.38) times more likely to heal. CONCLUSIONS: While no differences in healing were identified with supplementation in non-ischaemic patients or those with normal albumin, addition of arginine, glutamine and ß-hydroxy-ß-methylbutyrate as an adjunct to standard of care may improve healing of diabetic foot ulcers in patients with risk of poor limb perfusion and/or low albumin levels. Further investigation involving arginine, glutamine and ß-hydroxy-ß-methylbutyrate in these high-risk subgroups might prove clinically valuable.

Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial.

AIM: N-3 fatty acids, especially eicosapentaenoic acid (EPA), may possess anticachectic properties. This trial compared a protein and energy dense supplement enriched with n-3 fatty acids and antioxidants (experimental: E) with an isocaloric isonitrogenous control supplement (C) for their effects on weight, lean body mass (LBM), dietary intake, and quality of life in cachectic patients with advanced pancreatic cancer. METHODS: A total of 200 patients (95 E; 105 C) were randomised to consume two cans/day of the E or C supplement (480 ml, 620 kcal, 32 g protein +/- 2.2 g EPA) for eight weeks in a multicentre, randomised, double blind trial. RESULTS: At enrolment, patients' mean rate of weight loss was 3.3 kg/month. Intake of the supplements (E or C) was below the recommended dose (2 cans/day) and averaged 1.4 cans/day. Over eight weeks, patients in both groups stopped losing weight (delta weight E: -0.25 kg/month versus C: -0.37 kg/month; p = 0.74) and LBM (Delta LBM E: +0.27 kg/month versus C: +0.12 kg/month; p = 0.88) to an equal degree (change from baseline E and C, p<0.001). In view of evident non-compliance in both E and C groups, correlation analyses were undertaken to examine for potential dose-response relationships. E patients demonstrated significant correlations between their supplement intake and weight gain (r = 0.50, p<0.001) and increase in LBM (r = 0.33, p = 0.036). Such correlations were not statistically significant in C patients. The relationship of supplement intake with change in LBM was significantly different between E and C patients (p = 0.043). Increased plasma EPA levels in the E group were associated with weight and LBM gain (r = 0.50, p<0.001; r = 0.51, p = 0.001). Weight gain was associated with improved quality of life (p<0.01) only in the E group. CONCLUSION: Intention to treat group comparisons indicated that at the mean dose taken, enrichment with n-3 fatty acids did not provide a therapeutic advantage and that both supplements were equally effective in arresting weight loss. Post hoc dose-response analysis suggests that if taken in sufficient quantity, only the n-3 fatty acid enriched energy and protein dense supplement results in net gain of weight, lean tissue, and improved quality of life. Further trials are required to examine the potential role of n-3 enriched supplements in the treatment of cancer cachexia.

The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer.

Previous studies have suggested that administration of oral eicosapentaenoic acid (EPA) will stabilize weight in patients with advanced pancreatic cancer. The aim of the present study was to determine if a combination of EPA with a conventional oral nutritional supplement could produce weight gain in these patients. Twenty patients with unresectable pancreatic adenocarcinoma were asked to consume two cans of a fish oil-enriched nutritional supplement per day in addition to their normal food intake. Each can contained 310 kcal, 16.1 g protein and 1.09 g EPA. Patients were assessed for weight, body composition, dietary intake, resting energy expenditure (REE) and performance status. Patients consumed a median of 1.9 cans day(-1). All patients were losing weight at baseline at a median rate of 2.9 kg month(-1). After administration of the fish oil-enriched supplement, patients had significant weight-gain at both 3 (median 1 kg, P= 0.024) and 7 weeks (median 2 kg, P = 0.033). Dietary intake increased significantly by almost 400 kcal day(-1) (P = 0.002). REE per kg body weight and per kg lean body mass fell significantly. Performance status and appetite were significantly improved at 3 weeks. In contrast to previous studies of oral conventional nutritional supplements in weight-losing cancer patients, this study suggests that an EPA-enriched supplement may reverse cachexia in advanced pancreatic cancer.

[Use of G-CSF (Neupogen) in multimodal treatment in radiotherapy]. / Einsatz von G-CSF (Neupogen) bei multimodalen Therapiekonzepten in der Strahlentherapie.

BACKGROUND: Therapy-induced leukopenias with corresponding consequences repeatedly occur in radiotherapy using combined modalities treatment. In radiotherapy, where G-CSF (granulocyte-colony-stimulating-factor) is not licensed, G-CSF has been used successfully under individual circumstances. These results were confirmed in several studies with small patient groups. The aim of this study was to check former results in a larger patient group, to verify postulated side effects and specially to define a cost-effective schedule in the treatment with G-CSF (Neupogen). PATIENTS AND METHODS: In this surveillance trial 50, partially previously treated patients with different malignant tumors were treated with G-CSF. According to the probability of a leucocytosis lower than 1000/mm3, G-CSF (Neuropogen) was already given at leukocyte values lower than 2500/mm3 (500/mm3 bis 2450/mm3). It administered subcutaneously every other day, based on body weight until reaching normal leucocyte levels. RESULTS: In 92% of the patients the increase of leucocytes occurred in the first 24 hours. On average G-CSF was given 4.9 times per patient. Patients without prior therapies or less complex therapies needed less G-CSF applications (3.5 to 5.8 applications). Due to individually varying leucocyte courses the G-CSF therapy was started with leucocyte values between 500/mm3 and 2450/mm3. Patients who were treated with up to 3 G-CSF applications had higher leucocyte levels than those with 4 or more applications (1620/mm3 to 1250/mm3). Leucopenia related infections, therapy interruptions or break-offs did not occur. Besides light "flu like" symptoms in 14% of the patients, no side effects were observed. CONCLUSIONS: When a decrease of leucocyte values lower than 1000/mm3 is expected, the most cost-effective treatment is given when starting the interventional G-CSF administration already at leucocyte values around 1600/mm3. Leucopenias can be treated effectively, with little side effects and in a cost-effective way when G-CSF is given on time.

Meals-on-wheels applicants are a population at risk for poor nutritional status.

OBJECTIVE: To identify older adults with poor nutritional status among the independent-living elderly applying for meals-on-wheels, and to compare how a self-assessment tool and more traditional criteria identify nutritional risk. DESIGN: Descriptive study. SUBJECTS/SETTING: Meals-on-wheels applicants (n = 230 between 60 and 90 years of age (mean age = 77.4 +/- 7 years) who were free from terminal illness. Nutrition assessment data were collected in the home of each participant. MAIN OUTCOME MEASURES: Risk assessment for poor nutritional status was determined using anthropometric, dietary, and laboratory data and with a Nutrition Screening Initiative (NSI) self-assessment tool-the "DETERMINE Your Nutritional Health" checklist. STATISTICAL ANALYSES: Differences were assessed using Student's t test for unpaired data. RESULTS: Seventy-four percent of study participants were found to be at risk for poor nutritional status according to the study criteria, and 98% were at risk for poor nutritional status according to the NSI self-assessment tool. CONCLUSIONS: The majority of the applicants for meals-on-wheels were at risk for poor nutritional status. Thus, many independent-living older adults may need additional nutrition assessment and intervention to remain independent and in good nutritional status.

Malnutrition and clinical outcomes: the case for medical nutrition therapy.

Malnutrition is not a new or a rare problem. In studies involving more than 1,327 hospitalized adult patients, 40% to 55% were found to be either malnourished or at risk for malnutrition, and up to 12% were severely malnourished. Surgical patients with likelihood of malnutrition are two to three times more likely to have minor and major complications as well as increased mortality; and their length of stay can be extended by 90% compared with the stay of well-nourished patients. Hospital charges are reported to be from 35% to 75% higher for malnourished patients than for well-nourished patients. Obtaining data to assess the nutritional status of patients is essential to optimal patient care, especially for patients at high risk for malnutrition. Nutrition assessment can be done with readily available and relatively inexpensive methods. But it is not enough to assess and identify malnutrition. Outcomes are improved and costs are saved only when appropriate intervention follows. This article identifies many well-conducted, published studies that support the findings that health outcomes of malnourished patients can be improved and that overall use of resources can be reduced by nutrition counseling, oral diet and oral supplements, enteral formula delivered via tube, and parenteral nutrition support via central or peripheral line. Early nutrition assessment and appropriate nutrition intervention must be accepted as essential for the delivery of quality health care. Appropriately selected nutrition support can address the problem of malnutrition, improve clinical outcomes, and help reduce the costs of health care.

[Therapy trends in the prevention of radiation-induced diarrhea after pelvic and abdominal irradiation. Results of a tricenter study]. / Therapieansätze zur Prophylaxe der strahleninduzierten Diarrhoe nach Becken- und Abdominalbestrahlung. Ergebnisse einer trizentrischen Untersuchung.

PURPOSE: Radiotherapy induced diarrhea and convulsive pain are severe side-effects of irradiation of the pelvis and the abdomen leading often to an interruption of the treatment. Up to now these side-effects were only treated symptomatically, prophylactic therapies are not known. PATIENTS AND METHODS: During the years 1992 and 1993 174 patients who obtained radiotherapy in the pelvis or the abdomen because of different malignancies were observed referring to the diarrhea-prophylactic effect of Smectite (= Skilpin). 80 patients received Smectite at the beginning of radiotherapy, 94 patients of the control group were treated with motility modifying drugs when diarrhea appeared. The following parameters were compared: Frequency, consistence and incontinence of stool, tenesmus and the onset of diarrhea. RESULTS: 67.0% (n = 63) of the patients in the control group developed diarrhea, whereas in the pretreated Smectite-group only 37.5% of the cases (n = 30) developed diarrhea. The first appearance of diarrhea was at day 17 in the pretreated group and averagely at day 11 in the control group. 44% of the patients in the control group suffered from tenesmus versus 25% in the Smectite-group. CONCLUSION: In comparison to the symptomatic treatment of radiation enteritis the prophylactic application of Smectite is able to reduce the diarrhea from the beginning of radiotherapy or at least to reduce the pathological frequency of stool and therefore to increase the quality of life.

Regulation of the metabolism of linoleic acid to arachidonic acid in rat hepatocytes.

When 5 X 10(6) hepatocytes were incubated for 40 min with from 0.15 to 0.60 mM [1-14C]linoleic acid, [1-14C]6,9,12-octadecatrienoic acid, or [1-14C]8,11,14-eicosatrienoic acid, there was a concentration-dependent acylation of radioactive metabolites into both triglycerides and phospholipids. When the concentration of either [1-14C]linoleic acid or [1-14C]8,11,14-eicosatrienoic acid exceeded 0.3 mM, there was no further increase in the metabolism of either fatty acid to other (n-6) metabolites. When the concentration of [1-14C]6,9,12-octadecatrienoic acid exceeded 0.15 mM, there was an apparent substrate-induced inhibition in its metabolism to 8,11,14-eicosatrienoic acid. With all three substrates (0.3 mM), there was time-dependent metabolism to other (n-6) acids. Cells then were incubated simultaneously with 0.3 mM [1-14C]linoleic acid along with 0.15 to 0.45 mM 6,9,12-octadecatrienoic acid or 8,11,14-eicosatrienoic acid. These exogenous nonradioactive (n-6) acids suppressed but did not abolish the conversion of [1-14C]linoleate to radioactive arachidonate. These findings suggest that some linoleate is converted to arachidonate without intracellular mixing of 6,8,12-octadecatrienoic or 8,11,14-eicosatrienoic acids. This hypothesis is supported by the finding that exogenous linoleate did not markedly affect the metabolism of [1-14C]6,9,12-octadecatrienoic or [1-14C]8,11,14-eicosatrienoic acid by microsomal chain elongating or desaturating enzymes.

Metabolism of 6,9,12-octadecatrienoic acid and 6,9,12,15-octadecatetraenoic acid by rat hepatocytes.

When 5.10(6) hepatocytes were incubated for 40 min with 0.015-0.3 mM (1-14C)-labeled 6,9,12-octadecatrienoic acid or (1-14C)-labeled 6,9,12,15-octadecatetraenoic acid there was a concentration-dependent acylation of radioactive metabolites into both phospholipids and triacylglycerol. However, when the concentration of either substrate exceeded 60-150 microM there was no further increase in the metabolism of either substrate to longer-chain (n-6) and (n-3) acids. When cells were then incubated for various periods of time with 60 microM substrate there was initial rapid removal of the substrate which was accompanied by its acylation into lipids. Over time, the amount of both substrates in lipids declined without an overall drop in specific activity. This decline was accompanied by an increase in long-chain (n-6) and (n-3) fatty acids. Similar results were obtained when the time-dependent metabolism of the two substrates was examined in individual hepatocyte phospholipids. Collectively, these findings suggest that when these two 18-carbon acids are produced by desaturation of dietary linoleate and linolenate that they are in part initially acylated into a labile phospholipid pool. Rapid release and subsequent further metabolism to longer-chain (n-6) and (n-3) acids may explain why these products of the 6-desaturase do not accumulate in membrane lipids.

[Percutaneous radiotherapy in thyroid malignancies--curative and palliative viewpoints]. / Perkutane Strahlentherapie bei Schilddrüsenmalignomen--kurative und palliative Gesichtspunkte.

The treatment results of percutaneous radiotherapy of 85 patients with thyroid malignomas treated between 1972 and 1979 are presented in a retrospective study. 49 patients were treated for curative purposes, 36 patients suffering from metastases were submitted to palliative therapy. Primary radiotherapy was performed as pendulum or oblique-field irradiation up to 60 Gy, and patients with metastases or local recurrences were submitted to stationary-field or contralateral irradiation up to 40 (-50) Gy depending on the tumor site. In both groups, prognosis and survival time depend much more on the histologic differentiation than on the tumor dimension and the age of the patient. If the thyroid malignomas were well differentiated, we observed survival times of several years, even in case of extended, eventually filiarized tumors. On the other hand, the average survival time of patients with dedifferentiated thyroid tumors was only four months, with even worse results in case of only subtotally operable or completely inoperable anaplastic tumors. In these cases we should like to avoid an indication for percutaneous radiotherapy and to recommend, if possible, palliative surgical measures the effect of which will be seen more rapidly.

[Comparison of the therapeutic results in treating chronic myelosis with splenic irradiation or busulfan]. / Vergleich der Therapieergebnisse bei der Behandlung der chronischen Myelose mit Milzbestrahlung oder Busulfan.

In a retrospective study the survival of 111 patients with chronic myeloid leukemia was analyzed. There was a slight superiority of the patients primarily treated with busulfan over those first getting splenic irradiation and busulfan subsequently. This difference was statistically not significant. If spleen size prior to treatment was less than 10 cm below left costal margin, there was also a tendency in favor of primary busulfan therapy. In patients having bigger spleens, neither form of treatment had any advantage.

[Combined chemo- and radiotherapy of small cell bronchial carcinoma with high dosages of radiation]. / Kombinierte Chemo- und Radiotherapie des kleinzelligen Bronchial-karzinoms mit Anwendung hoher Strahlendosen.

35 patients with small cell carcinoma of the lung were treated with adriamycin, cyclophosphamide and vincristine according to the ACO-protocol. Between the third and fourth course of chemotherapy the primary tumor region was irradiated with a dose of 50 to 60 Gy. In addition, the cranium and the parts of the mediastinum, which were not yet invaded by the tumor received irradiation with 30 Gy. The complete remission rate was 71% (10 out of 14 patients) in limited disease and 29% (6 out of 21 patients) in extensive disease. The median survival time was 13 months in LD and 7 in ED. The relapses occurred mainly outside the fields of the radiation. Only 3 of the 16 patients who achieved a complete remission relapsed in the irradiated field. In contrast to the results obtained with combined chemo- and radiotherapy with doses of only 30-40 Gy to the primary area, there was better local control of the tumor but without a better remission rate or survival time. The toxicity was not increased by the high dose irradiation.

[Combination treatment of small cell bronchial carcinoma]. / Zur kombinierten Behandlung des kleinzelligen Bronchialkarzinoms.

35 cases with micro-cellular bronchial carcinoma are described. The patients are treated with a combination of a modified ACO scheme and fractionated irradiations with 50 to 60 Gy to the primary tumor and 30 Gy to the encephalic skull. Among 14 patients with local disease, ten had a complete remission and three a partial remission. Among 21 patients with advanced disease, six had a complete remission and eight a partial remission. The side effects were not important, and they were not reinforced by the higher dose of the primary irradiation. The local recurrence rate was decreased, but the average survival times were not prolonged, because these are still dependent upon the hematogenic formation of metastases.