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Biomedical subjects

M B Jensen

Publications and source records attributed to M B Jensen.

At least 37 records · Page 2Linked to original sources

Impact of axillary dissection on staging and regional control in breast tumors < or = 10 mm--the DBCG experience. The Danish Breast Cancer Cooperative Group (DBCG), Rigshisoutalet, Copenhagen, Denmark.

Data from 4771 patients with tumor diameters < or = 10 mm were analyzed. Results of surgery and pathoanatomical examinations indicated that nodal status was related to diameter, but not to number of nodes removed. More axillary metastases were found in group T1b tumors than in T1a. In 8% of tumors, at least 4 positive nodes were identified. Mean number of positive nodes was related to number of nodes removed, and when 10 or more nodes were removed a significantly lower axillary recurrence rate and better recurrence-free survival were demonstrated, confirming that axillary surgery has two goals: staging and regional disease control. Age, receptor status, grade and histological type, but not tumor location, were related to prognosis. In accordance with the classical prognostic factors, it was not possible to define a patient group where axillary surgery was superfluous. We conclude that proper staging and regional control renders a full axillary level I-II dissection necessary.

Adult↗

[Effect of specific physiotherapy on chronic pain, functional level and quality of life in osteoporosis. A prospective randomized single-blind placebo-controlled study].

Patients suffering from osteoporotic vertebral fractures are handicapped by pain and reduced quality of life. Our aim was to investigate the effect of a short training program for osteoporotic patients with regard to pain level, use of analgetics and quality of life. We performed a prospective randomized single-blinded placebo-controlled study. The training program included general training of balance and muscle strength and stabilization of the back. The participants were randomised to 10 weeks of ambulatory training. Controls and training participants were tested weekly by registration of pain level and analgetic intake. Questionnaires on daily level of function and quality of life were given at the start and after five and 10 weeks. After three months both groups filled out the questionnaires at home. The training group had a significant reduction in pain score and use of analgetics. The distribution of functional score improved during training. Quality of life score improved significantly throughout the study and after three months. In conclusion, this ambulatory training program is effective for training osteoporotic patients with moderately severe pain and the training should be continued.

Aged↗

Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial.

BACKGROUND: Postmastectomy radiotherapy is associated with a lower locoregional recurrence rate and improved disease-free and overall survival when combined with chemotherapy in premenopausal high-risk breast-cancer patients. However, whether the same benefits apply also in postmenopausal women treated with adjuvant tamoxifen for similar high-risk cancer is unclear. In a randomised trial among postmenopausal women who had undergone mastectomy, we compared adjuvant tamoxifen alone with tamoxifen plus postoperative radiotherapy. METHODS: Between 1982 and 1990, postmenopausal women with high-risk breast cancer (stage II or III) were randomly assigned adjuvant tamoxifen (30 mg daily for 1 year) alone (689) or with postoperative radiotherapy to the chest wall and regional lymph nodes (686). Median follow-up was 123 months. The endpoints were first site of recurrence (locoregional recurrence, distant metastases, or both), and disease-free and overall survival. FINDINGS: Locoregional recurrence occurred in 52 (8%) of the radiotherapy plus tamoxifen group and 242 (35%) of the tamoxifen only group (p<0.001). In total there were 321 (47%) and 411 (60%) recurrences, respectively. Disease-free survival was 36% in the radiotherapy plus tamoxifen group and 24% in the tamoxifen alone group (p<0.001). Overall survival was also higher in the radiotherapy group (385 vs 434 deaths; survival 45 vs 36% at 10 years, p=0.03). INTERPRETATION: Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection, with 1 year of adjuvant tamoxifen treatment. Improved survival in high-risk breast cancer can best be achieved by a strategy of both locoregional and systemic tumour control.

Antineoplastic Agents, Hormonal↗

Microglial reactivity correlates to the density and the myelination of the anterogradely degenerating axons and terminals following perforant path denervation of the mouse fascia dentata.

Transection of the entorhino-dentate perforant path is a well known model for lesion-induced axonal sprouting and glial reactions in the rat. In this study, we have characterized the microglial reaction in the dentate molecular layer of the SJL/J and C57Bl/6 mouse. The morphological transformation of the microglial cells and their densitometrically measured Mac-1 immunoreactivity were correlated with the density of silver-impregnated axonal and terminal degeneration and the myelination of the degenerating medial and lateral perforant pathways. Anterograde axonal and terminal degeneration leads to: (i) altered myelin basic protein immunoreactivity with the appearance of discrete myelin deposits preferentially in the denervated medial and significantly less so in the lateral perforant path zone from day 2 after lesioning; (ii) an increase in number and Mac-1 immunoreactivity of morphologically-changed microglial cells in the denervated perforant path zones with more pronounced morphological transformation of microglia in the medial than in the lateral perforant path zones at day 2 but not day 5 after lesioning; and (iii) a linear correlation between the density of microglial Mac-1 reactivity and axonal degeneration in the medial but not in the lateral perforant path zone at two days postlesion, and a linear correlation in both zones at five days postlesion. We propose that the differentiated microglial response is due to the different densities of axonal and terminal degeneration, as observed in the individual cases. The finding of a potentiated or accelerated microglial activation in the medial as compared to the lateral perforant path zone suggests different kinetics of microglial activation in areas with degenerating myelinated and unmyelinated fibers.

Animals↗

Tamoxifen in high-risk premenopausal women with primary breast cancer receiving adjuvant chemotherapy. Report from the Danish Breast Cancer co-operative Group DBCG 82B Trial.

Following modified radical mastectomy, pre- and perimenopausal (amenorrhoea for < 5 years) patients with stage II or III breast cancer received CMF (cyclophosphamide 600, methotrexate 40, 5-fluorouracil 600 mg/m2 intravenously (i.v.) every 4 weeks, 9 cycles). The effect on recurrence-free survival (RFS) and overall survival (OS) of the addition of adjuvant tamoxifen (TAM) to adjuvant chemotherapy was examined by randomisation either to no additional treatment (n = 314), or concurrently TAM 30 mg daily for 1 year (n = 320). 40% had positive, 12% negative and 48% unknown receptor status. One year after surgery 21% versus 35% (CMF + TAM versus CMF) were still menstruating (P < 0.01). With a median follow-up of 12.2 years there was no difference in RFS (10-year RFS 34% versus 35%, P = 0.81) or OS (45% versus 46%, P = 0.73). In a Cox proportional hazards model, tumour size, number of metastatic lymph nodes, frequency of metastatic nodes in relation to total number of nodes removed, degree of anaplasia, age, and menostasia within the first year after operation were significant independent prognostic factors for RFS, and the same factors except age for OS. No significant interactions with TAM were seen. Thus, in this group of pre- and perimenopausal high-risk early breast cancer patients with heterogeneous receptor status given CMF i.v., concurrent TAM for 1 year did not improve the outcome. These results do not exclude that receptor positive patients may benefit from adjuvant TAM for longer periods given sequentially to chemotherapy.

Adult↗

Perioperative growth hormone treatment and functional outcome after major abdominal surgery: a randomized, double-blind, controlled study.

OBJECTIVE: To evaluate short- and long-term effects of perioperative human growth hormone (hGH) treatment on physical performance and fatigue in younger patients undergoing a major abdominal operation in a normal postoperative regimen with oral nutrition. SUMMARY BACKGROUND DATA: Muscle wasting and functional impairment follow major abdominal surgery. METHODS: Twenty-four patients with ulcerative colitis undergoing ileoanal J-pouch surgery were randomized to hGH (12 IU/day) or placebo treatment from 2 days before to 7 days after surgery. Measurements were performed 2 days before and 10, 30, and 90 days after surgery. RESULTS: The total muscle strength of four limb muscle groups was reduced by 7.6% in the hGH group and by 17.1% in the placebo group at postoperative day 10 compared with baseline values. There was also a significant difference between treatment groups in total muscle strength at day 30, and at the 90-day follow-up total muscle strength was equal to baseline values in the hGH group, but still significantly 5.9% below in the placebo group. The work capacity decreased by approximately 20% at day 10 after surgery, with no significant difference between treatment groups. Both groups were equally fatigued at day 10 after surgery, but at day 30 and 90 the hGH patients were less fatigued than the placebo patients. During the treatment period, patients receiving hGH had reduced loss of limb lean tissue mass, and 3 months after surgery the hGH patients had regained more lean tissue mass than placebo patients. CONCLUSIONS: Perioperative hGH treatment of younger patients undergoing major abdominal surgery preserved limb lean tissue mass, increased postoperative muscular strength, and reduced long-term postoperative fatigue.

Adolescent↗

Positive effects of physiotherapy on chronic pain and performance in osteoporosis.

The aim of this placebo-controlled, randomized, single-masked study was to establish the effects of a 10-week ambulatory exercise programme for osteoporotic patients on pain, use of analgesics, functional status, quality of life, balance and muscle strength. Fifty-three ambulatory postmenopausal women with at least one spinal crush fracture and pains within the last 3 years were randomized for physiotherapeutic training twice a week for 10 weeks or no training. The training included general training of balance and muscle strength, with stabilization of the lumbar spine. The participants were tested at baseline, week 5 and week 10 with a balance test, muscle strength test and questionnaires on pain, use of analgesics, functional status and quality of life. Twelve weeks after the supervised training had finished (week 22) they answered the same questionnaires. The study groups were comparable at baseline. The training group had a significant reduction in use of analgesics (p = 0.02) and pain level (p = 0.01) during the training period. Distribution of functional score improved; the improvement was reduced at week 22. Quality of life score improved significantly throughout the study (p = 0.0008), even after week 22. Balance improved non-significantly (p = 0.08). Quadriceps muscle strength improved significantly after 5 weeks (p = 0.04). Back extensor muscle strength improved almost significantly (p = 0.09). In conclusion, this training programme for osteoporotic patients improved balance and level of daily function and decreased experience of pain and use of analgesics. Quality of life was improved even beyond the active training period.

Aged↗

The importance of surgery and accurate axillary staging for survival in breast cancer.

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.

Adult↗

EMLA patch for spinal puncture. A comparison of EMLA patch with lignocaine infiltration and placebo patch.

We have prospectively assessed pain and anxiety of spinal puncture in 180 adult patients randomly allocated to one of three equal groups. On the morning of surgery group 1 had an EMLA patch, whereas group 2 and 3 had placebo patches. Group 2 also had infiltration analgesia with 2 ml lignocaine 2% with adrenaline, immediately before the block. Spinal anaesthesia was performed with 25 gauge sharp needles without introducer or 25,27 gauge blunt needles with 20,22 gauge introducers. Patients assessed the spinal puncture pain on a 10-cm visual analogue scale immediately after removal of the needle. Pain scores were significantly lower in group 1 (EMLA), median 0.75, than in group 2 (placebo, infiltration analgesia), median 1.75, and group 3 (placebo), median 1.80, p < 0.0001. Pain intensity was less than expected in more patients in the EMLA group than in the other two groups, p = 0.034. However, the decision to accept/reject spinal anaesthesia in the future was not influenced by the pain of lumbar puncture. We conclude that application of an EMLA patch is a simple and effective method to provide adequate analgesia for spinal puncture, which also helps to allay patients' fears of spinal anaesthesia.

Administration, Cutaneous↗

Growth hormone treatment improves body fluid distribution in patients undergoing elective abdominal surgery.

OBJECTIVE: To investigate the possible beneficial effects of growth hormone (GH) in catabolic patients we examined the impact of GH on body fluid distribution in patients with ulcerative colitis undergoing elective abdominal surgery. DESIGN AND MEASUREMENTS: Twenty-four patients (14 female, 10 male) aged 19-47 years were in a double-blinded study randomly assigned to receive either placebo (n = 12) or GH (n = 12) 6 i.u. s.c. twice daily from 2 days before until 7 days after ileo-anal J pouch surgery. Extracellular and plasma volume (ECV, PV) were determined using 82Br and 125I albumin dilution at day -2 and at day 7, and body composition was estimated by dual X-ray absorptiometry and bioimpedance. Changes in body weight and fluid balance were recorded and hence intracellular volume was assessed. RESULTS: During placebo treatment body weight decreased 4.3 +/- 0.6 kg; during GH treatment body weight was constant (P < 0.01). There was a positive fluid balance in the GH-treated patients compared to the placebo group (GH: 3.6 +/- 0.7 l; plc: -0.7 +/- 1.2 l, P < 0.01). ECV increased 2.12 +/- 0.70 l during GH and was unaffected during placebo (P = 0.02). PV was unchanged by GH and decreased 0.39 +/- 0.08 l during placebo administration (P = 0.03). Intracellular volume (ICV) decreased less during GH than during placebo (GH: -1.42 +/- 0.45; plc: -3.70 +/- 0.76; P = 0.02). Bioimpedance remained constant during GH administration and increased 60 +/- 9 ohm in the placebo-treated group (P < 0.05). Plasma renin and aldosterone remained unchanged in both study groups. CONCLUSION: Body weight, plasma volume and intracellular volume is preserved during GH treatment in catabolic patients and ECV is increased. From a therapeutic point of view these effects may be desirable under conditions of surgical stress.

Adult↗

Perioperative growth hormone treatment increases nitrogen and fluid balance and results in short-term and long-term conservation of lean tissue mass.

The surgical procedure for forming an ileoanal anastomosis with a J pouch (IAA) usually involves a temporary ileostomy; patients undergoing IAA surgery thus need to recover quickly because they return for ileostomy closure 3 mo later. We evaluated the effects of perioperative biosynthetic growth hormone (GH) treatment on short- and long-term changes in body composition and on nutritional intake. Patients with ulcerative colitis undergoing IAA surgery were randomly assigned to double-blind treatment with placebo (n=12) or 6 IU GH twice daily (n=12) from 2 d before to 7 d after the operation. Examinations were from 2 d before to 9 d after the operation and on days 30 and 90. Body composition was assessed with a dual-energy X-ray absorptiometry scanner. The 2 groups had similar nutritional intakes. On postoperative day 7, placebo-treated patients had lost 4.2 kg (95% CI: 3.0, 5.4) total tissue mass, 3.6 kg (2.1, 5.1) lean tissue mass, and 0.5 kg (-0.1, 1.2) fat mass. These reductions persisted 3 mo later. Compared with placebo, GH improved nitrogen balance, changes in lean tissue mass [gain of 4.0 kg (1.9, 6.0), P=0.001], and changes in total tissue mass [gain of 3.2 kg (1.6, 4.9), P=0.001], but increased the loss of fat mass [loss of 0.7 kg (0.0, 1.5), P=0.049] on postoperative day 7. Three months later, the placebo-treated patients had lost 2.4 kg (0.7, 4.2) more lean tissue mass than GH-treated patients (P=0.009), whereas changes in total tissue and fat mass were not significantly different. Hence, GH treatment enhanced the long-term regain of lean tissue mass.

Absorptiometry, Photon↗

Differential changes in free and total insulin-like growth factor I after major, elective abdominal surgery: the possible role of insulin-like growth factor-binding protein-3 proteolysis.

Major surgery is accompanied by extensive proteolysis of insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3). Proteolysis of IGFBP-3 is generally believed to increase IGF bioavailability due to a diminished affinity of the IGFBP-3 fragments for IGFs. We have investigated 18 patients undergoing elective ileo-anal J-pouch surgery. Patients were randomized to treatment with GH (12 IU/day; n = 9) or placebo (n = 9) from 2 days before to 7 days after operation. Free IGF-I and IGF-II were measured by ultrafiltration of serum, and IGFBP-3 proteolytic activity was determined by a [125I]recombinant human IGFBP-3 degradation assay. In the GH-treated group, total IGF-I increased preoperatively by 99%. Postoperatively, total IGF-I decreased by 48% (placebo) and 52% (GH). Immunoassayable IGFBP-3 decreased by 27% (placebo) and 26% (GH). In the placebo-treated group, free IGF-I was unchanged throughout the study. In the GH-treated group, free IGF-I increased by 277% preoperatively and remained elevated after operation. IGFBP-3 proteolytic activity increased by 63-73% after operation. The relative elevations of free IGF-I levels despite decreased total IGF-I levels could thus relate to augmented IGFBP-3 proteolysis.

Adult↗

Continuous infusion of recombinant activated factor VII: stability in infusion pump systems.

Recombinant activated factor VII (rFVIIa; NovoSeven, Novo Nordisk, Bagsvaerd, Denmark) has a half life of 2.8 h in vivo, necessitating frequent dosing to maintain haemostasis where administration is by bolus injection. Continuous infusion would avoid this frequent dosing and potentially reduce the amount of rFVIIa used and the cost of treatment. We investigated the stability of reconstituted rFVIIa solutions alone and with the addition of heparin, low-molecular-weight heparin (LMWH, enoxaparin) and saline solution. Recombinant FVIIa was stable in the infusion pump for several days at room temperature and for 24 h at body temperature. Addition of heparin at pH 7 and LMWH and saline did not significantly affect the activity of rFVIIa for periods of 2 h, 72 h and 30 min, respectively. Recombinant FVIIa continuous infusion systems prepared under strict aseptic conditions remained free from significant microbiological contamination for 24 h.

Anticoagulants↗

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗

Should women be advised against pregnancy after breast-cancer treatment?

BACKGROUND: Oestrogen is an established growth factor in breast cancer. There has, therefore, been much discussion about whether women should be advised against becoming pregnant after breast-cancer treatment because of a possible negative prognostic effect from the high oestrogen concentrations associated with pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information on these women was obtained from the Danish Breast Cancer Cooperative Group. Since 1977 this group has collected population-based data on tumour characteristics, treatment regimens, and follow-up status of Danish women with breast cancer. Details of reproductive history were obtained from The Danish Civil Registration System, the National Birth Registry, and the National induced Abortion registry. We estimated the relative risk of death among women who became pregnant after breast-cancer treatment compared with women who had not become pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of younger at the time of diagnosis were followed up for 35,067 patient-years. Among these, 173 women became pregnant after treatment of breast cancer. Women who had a full-term pregnancy after breast-cancer treatment had a non-significantly reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women who had had no full-term pregnancy after adjustment for age at diagnosis, stage of disease (tumour size, axillary nodal status, and histological grading), and reproductive history before diagnosis. The effect was also not significantly modified by age at diagnosis, tumour size, nodal status, or reproductive history before diagnosis of breast cancer. Neither miscarriages nor induced abortions after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found no evidence that a pregnancy after breast-cancer treatment increased the risk of a poor outcome.

Abortion, Induced↗

[Treatment of cancer pain in Denmark. A questionnaire survey].

A questionnaire survey was carried out with the aim of evaluating knowledge about and practice of cancer pain treatment in Denmark. A questionnaire was sent to a 10% random sample of Danish physicians. Of these 1411 physicians, 1068 (76%) returned the questionnaires and after the exclusion of those doctors who never treated cancer patients, 577 (54%) were analyzed. Their knowledge of the principles and practice of cancer pain treatment was evaluated by means of 14 multiple-choice and open questions. Their ability to apply their knowledge in practice was evaluated by analyzing their suggested treatment of three simulated patient cases. Ninety-seven percent of the physicians recognized difficulties in cancer pain treatment, the most frequent being side effects of drugs and inadequate pain relief. It appeared from the proposals for pain treatment of the patient cases that the majority of the physicians could treat both pain from bone metastasis (75%) and visceral pain (78%) satisfactorily, while very few suggested coanalgesics for neuropathic pain (20%). Older physicians performed less satisfactorily than did their younger colleagues. Basic pain treatment skills have been acquired by the Danish physicians. However, in the future emphasis should be placed on the treatment of neuropathic pain with coanalgesics and the management of opioid side-effects.

Analgesia↗

[The significance of nutrition for muscular function after surgery].

Major surgery is accompanied by weight loss and reduced muscular strength; the weight loss can be lessened by giving protein- and energy-rich supplements during the postoperative period. Large weight losses always reduce muscular function, but when can it be expected that a weight loss has importance for the muscular function of surgical patients? This review argues that for patients undergoing gastro-intestinal surgery weight losses of more than 10% can be expected to impair muscular function; the impact of weight losses below 10% has not been studied much. It is dubious whether a small weight loss would be of importance for muscular function, however, the muscular function of very old patients may be particularly vulnerable to weight loss due to the reduction in skeletal muscle mass in old age.

Dietary Carbohydrates↗