Psychological distress and health-related quality of life among stable patients with bronchiectasis.

BACKGROUND: Bronchiectasis is characterized by chronic symptoms and impaired physical activity. Anxiety and depression usually complicate chronic illness. Thus, underdiagnosis of psychological distress in bronchiectasis may lead to increased morbidity and mortality. AIMS: The aim of this study is to evaluate the impact of physical illness on psychological distress and its association with health-related quality of life (HRQOL). SUBJECTS AND METHODS: This is a cross-sectional study of adults with bronchiectasis. Patients completed a study questionnaire, the hospital anxiety and depression scale and the World Health Organization quality of life brief (WHOQOL-BREF) questionnaire. Physical examination was conducted on all participants. RESULTS: 103 patients were recruited for this study: 54 males (52.4%) and 49 females (47.6%). The average age of the patients was 49.12 ± 14.37 years. The most common predisposing factor for bronchiectasis amongst the patients was previous pulmonary tuberculosis (51 patients, 49.5%). Chronic productive cough, which was reported by 98 of the subjects (95.15%), was the most common symptom. 89 subjects (86.41%) reported episodes of shortness of breath, 82 (79.61%) reported at least one episode of exacerbation, while 52 subjects (50.49%) were hospitalized for bronchiectasis in the previous 12 months. 23 subjects (22.3%) had anxiety and 32 (31.1%) had depression. Anxiety and depression were significantly associated with indicators of severe disease. The subjects recorded low HRQOL scores across all domains. Psychological distress displayed a significant negative association with all the quality-of-life domains except between anxiety and social interaction. CONCLUSION: Symptoms of depression and anxiety are common among patients with bronchiectasis and these symptoms have a negative impact on HRQOL.

Interventions in the management of infection in the foot in diabetes: a systematic review.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients.

The microbiome of diabetic foot osteomyelitis.

The purpose of this investigation was to evaluate the diversity of bacteria in diabetic foot osteomyelitis using a 16S rRNA sequencing approach and to compare the results with conventional culture techniques. In this prospective observational study, we obtained 34 bone samples from patients admitted to our hospital with a moderate-severe diabetic foot infection. We analysed the distribution of the 16S rRNA gene sequences in the bone samples, using an Illumina MiSeq Personal Sequencer. We compared the genera that were detected with the cultured pathogens in the bone samples with conventional techniques. In the 23 samples that had positive results with both techniques, Staphylococcus, Corynebacterium, Streptococcus and Propionibacterium spp. were detected in 20, 18, 13 and 11 samples, respectively. Significantly more anaerobes were detected with 16S rRNA sequencing compared to conventional techniques (86.9 % vs. 23.1 %, p = 0.001) and more Gram-positive bacilli were present (78.3 % vs. 3.8 %, p < 0.001). Staphylococcus spp. were identified in all of the sequenced bone samples that were negative with conventional techniques. Mixed genera were present in 83.3 % (5 of 6) of the negative samples. Anaerobic and fastidious organisms may play a more significant role in osteomyelitis than previously reported. Further studies with larger populations are needed in order to fully understand the clinical importance of the microbial diversity of diabetic foot osteomyelitis.

The effect of lower extremity nerve decompression on health-related quality of life and perception of pain in patients with painful diabetic polyneuropathy: a prospective randomized trial.

AIMS: The aim of this study was to assess whether surgical decompression of nerves in the lower extremity in people with painful diabetic polyneuropathy would have an effect on health-related quality of life and to determine minimal clinically important differences in pain and quality of life scores. METHODS: The design was a randomized controlled trial in which 42 participants with painful diabetic painful neuroapthy underwent unilateral decompression of nerves in their left or right leg, using the other leg as a control, with 12 months follow-up. Surgical decompression was performed at the tibial, superficial, deep and common peroneal nerves. Preoperatively, and at 6 and 12 months post operatively, a visual analogue scale for pain and the 36 item short-form health survey and EuroQual 5 Dimensions questionnaires were completed. RESULTS: At 12 months follow-up, the visual analogue scale was significantly reduced, but decompression surgery did not significantly alter health-related quality of life scores. The minimal clinically important difference for visual analogue scale reduction was determined at 2.9 points decrease, a threshold reached by 42.5% of the study population. CONCLUSIONS: Although decompression surgery does not influence health-related quality of life, it achieves a clinically relevant reduction of pain in ~42.5% of people with diabetic peripheral neuropathy. It can therefore be considered for patients who do not adequately respond to pain medication.

Are clindamycin and ciprofloxacin appropriate for the empirical treatment of diabetic foot infections?

The objective of this study was to determine if specific species of microorganisms are associated with severe infection and amputation in patients with a diabetic foot infection and to evaluate the effectiveness of clindamycin and ciprofloxacin in this population. A retrospective cohort study was performed at the University Medical Center Utrecht, The Netherlands, for the period January 1st 2005 to January 1st 2010. Patients with ICD-9 codes 'diabetic foot' were selected from the hospital database. We evaluated the association of Staphylococcus aureus and Gram-negative species (GNS) with severity of infection, number of amputations, and healing rates. No significant association was found between the different microorganisms and infection severity. Coinfections of GNS and S. aureus were significantly associated with amputation compared to infections with only S. aureus [p = 0.016, odds ratio (OR) 4.9, confidence interval (CI) 1.4-16.9]. The empiric antibiotic regimen of clindamycin and ciprofloxacin covered only 85 % of S. aureus and 78 % of GNS diabetic foot infections. In mild diabetic foot infection in the studied population, where methicillin-sensitive S. aureus and streptococci are the most likely pathogens, a beta-lactam antibiotic such as flucloxacillin would likely be more effective than clindamycin. In moderate and severe infections, where GNS as a causative organism cannot be safely excluded, broad-spectrum antibiotic therapy may be more adequate.

Antimicrobials and Non-healing Wounds Evidence, controversies and suggestions.

Non-healing wounds are a significant problem for health-care systems worldwide. In the industrialised world, almost 1-1.5% of the population will have a problem wound at any one time. Furthermore, wound management is expensive; in Europe, the average cost per episode is 6650 euros for leg ulcers and 10 000 euros for foot ulcers, and wound management accounts for 2-4% of health-care budgets. These figures are expected to rise along with an increased elderly and diabetic population.1-4.

A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot.

The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot.

Expert opinion on the management of infections in the diabetic foot.

This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations.

Novel loci for major depression identified by genome-wide association study of Sequenced Treatment Alternatives to Relieve Depression and meta-analysis of three studies.

We report a genome-wide association study (GWAS) of major depressive disorder (MDD) in 1221 cases from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 1636 screened controls. No genome-wide evidence for association was detected. We also carried out a meta-analysis of three European-ancestry MDD GWAS data sets: STAR*D, Genetics of Recurrent Early-onset Depression and the publicly available Genetic Association Information Network-MDD data set. These data sets, totaling 3957 cases and 3428 controls, were genotyped using four different platforms (Affymetrix 6.0, 5.0 and 500 K, and Perlegen). For each of 2.4 million HapMap II single-nucleotide polymorphisms (SNPs), using genotyped data where available and imputed data otherwise, single-SNP association tests were carried out in each sample with correction for ancestry-informative principal components. The strongest evidence for association in the meta-analysis was observed for intronic SNPs in ATP6V1B2 (P=6.78 x 10⁻7), SP4 (P=7.68 x 10⁻7) and GRM7 (P=1.11 x 10⁻6). Additional exploratory analyses were carried out for a narrower phenotype (recurrent MDD with onset before age 31, N=2191 cases), and separately for males and females. Several of the best findings were supported primarily by evidence from narrow cases or from either males or females. On the basis of previous biological evidence, we consider GRM7 a strong MDD candidate gene. Larger samples will be required to determine whether any common SNPs are significantly associated with MDD.

The outcome of conservative treatment of fifth metatarsal diaphyseal fractures.

INTRODUCTION: The fifth metatarsal diaphyseal fracture is a common fracture. However, clear consensus about the treatment is lacking. Unlike the avulsion fracture or Jones' fracture, literature available on the treatment and long-term outcome of the diaphyseal fracture is scarce.The purpose of this study is to demonstrate a substantial number of conservatively treated patients with persistent pain and to evaluate metatarsal shortening and displacement within this group. METHODS: In this retrospective study, 106 patients who had experienced a fifth metatarsal diaphyseal fracture were included and evaluated. The minimum follow-up period was three months. FAAM, AOFAS and NRS scores were used as outcome measurements for function and pain. Length and displacement were analysed on plain X-rays. RESULTS: At least 11% of the patients who received conservative treatment for their fifth metatarsal diaphyseal fracture had persistent pain at least 3 months after initiation of conservative treatment. No relationship has been found between the length of the fifth metatarsal and the FAAM (r( Petrisor et al., 2006) 2 = 0,051), AOFAS (r( Petrisor et al., 2006) 2 = 0,009) and NRS (r( Petrisor et al., 2006) 2 = 0,001). Furthermore, there was no association between patients with a shorter fifth metatarsal and FAAM, AOFAS, NRS, displacement and BMI. DISCUSSION AND CONCLUSION: The finding of persistent pain in at least 11% of all patients at long-term follow-up confirms our hypothesis on long-term symptoms. However, the results suggest that these persistent symptoms are not related to metatarsal shortening or displacement.

Effectiveness and safety of adjustable maintenance dosing with budesonide/formoterol turbuhaler compared with traditional fixed doses in bronchial asthma: a multi-centre Nigerian study.

The modern treatment guideline of bronchial asthma recognize that combination of long acting beta2-agonists and inhaled glucocorticoids, enables better control of inflammation and symptoms of asthma than inhaled glucocorticoids only. These guidelines recommended that patients are educated to adjust their medication to their asthma severity using physician-guided self-management plans. However, many patients take a fixed dose of their controller medication and adjust their reliever medication to asthma symptoms Therefore, combination of formoterol and budesonide can be delivered at different dosing level without the need to change inhalers. This study examined whether asthma control improved if patients adjusted the maintenance doses(AMD) ofbudesonide/formoterol (Symbicort, 80/ 4.5 microg and 160/4.5 microg) according to asthma severity compared with traditional fixed dosing (FD) regimens. This was a prospective open randomized trial carried out in five teaching hospitals across Nigeria between 15th July 2002 and 15th July 2003. Patients with bronchial asthma who met the enrollment criteria were randomized to receive either adjustable dosing or fixed dosing for a period of twelve weeks. The results obtained at the start and the end of the study showed that budesonide/formoterol combination effectively achieved and maintained control of asthma. The adjustable dosing achieves more effective control compared to fixed dosing in terms of the number of patients that are redistributed to less severe forms of persistent asthma. The percentage of patients with intermittent asthma increased from 9.3% at randomization to 55.6% at the end of therapy with more patients at the AMD arm of treatment. Also for mild persistent asthma there was an increase from 20.4% to 24.1%. This showed that at the end of treatment, majority (79.7%) of the patients had intermittent and mild persistent asthma. The frequency of use of budesonide/formoterol in the two arms of treatment showed that patients in the adjustable groups used less number of inhalations of budesonide/formoterol for treatment on average of 2.5 inhalations per day compared to those on fixed dosing who used 4 inhalations per day (p = 0.0001). The number of times patients stayed awake because of asthma was noticed to be more reduced at the adjustable arm of treatment but this was of no statistical significance. It is therefore concluded, that budesonide/formoterol combination in a single inhaler is a simple, well tolerated, convenient treatment which provides effective control of bronchial asthma using a practical self-management plan consistent with current guidelines.

Knowledge and perception of HIV prevention through condom use among midlife and older adults in Calabar, Nigeria.

OBJECTIVES: Older people are at increasing risk of HIV/AIDS and other sexually transmitted diseases. The use of condoms which can protect both partners from sexually transmitted infections (STIs) including HIV during vaginal and anal sex is mostly neglected by them. In fact, postmenopausal women may not see the need for condom use when they are no longer at risk for pregnancy. Even though HIV/AIDS in older patients carry a high mortality, it is many times neglected by even healthcare providers because of the belief that older persons are no longer sexually active. This study aimed to determine the perception and knowledge of condom use as a strategy for HIV/AIDS prevention among midlife and older adults in Calabar Nigeria. METHOD: A cross-sectional study was carried out to identify the perception and knowledge of HIV transmission and condom use among adults over 50 years ofage, in the University of Calabar Teaching Hospital, Calabar, Nigeria. A structured questionnaire was used to get the demographic data, sources of information about the disease, knowledge about the use of condom and its efficacy in preventing the disease. RESULTS: A total of 488 participants were interviewed, comprising 263 males (53.9%) and 225 females (46.1%). Most of them (83.8%) were married and the rest (16.2%) were single. The majority of the respondents (368, 75.7%) got their information about HIV/AIDS transmission and prevention from the television. Other sources of information for respondents on HIV/AIDS were awareness campaigns (43.5%), newspapers (38.6%), friends (37.3%) and neighbours (27.1%). Three hundred and four (62.3%) of the respondents said that they had used condoms and believed that condoms could effectively prevent transmission of STIs including HIV compared to the one hundred and eighty-four (31.7%) who opined otherwise. Abstinence was the major mode of prevention of the disease among respondents while unprotected sexual intercourse was identified by the majority of the respondents (87.5%) as a high risk factor CONCLUSION: There should be more public education on HIV/AIDS to midlife and older adults.

Influence of ethnicity on pharmacogenetic variation in the Ghanaian population.

It has been well established that the frequencies of genomic variants can vary greatly between the populations of different countries. We sought to quantify the intra-population variability in Ghana to determine the value of genotyping studies done at a nationwide level. Further, we investigated the differences between the Ghanaian and other African populations to determine the quality of genomic representation provided by a small subgroup within the continent with regard to the general population. We genotyped 934 unrelated Ghanaian individuals for 15 single nucleotide polymorphisms (SNPs) from genes defined as clinically relevant based on their reported roles in the transport of, metabolism of, or as targets of the medicines listed in the World Health Organization Essential Medicines list. Populations within Ghana and between nations in Western Africa were genetically cohesive. In contrast, populations in other areas of Africa were genetically divergent. Gene allele frequency also differed significantly between the populations in African nations and the United States for several of the SNPs. These results demonstrate that national populations in similar geographic regions, like Africa, may have widely varying genetic allele frequencies for clinically relevant SNPs. Further genotyping studies of specific populations are necessary to provide the best medical care to all individuals.

Diverse blood exposures associated with incident HIV infection in Calabar, Nigeria.

Few types of blood exposures have been assessed in relation to incident HIV infection in sub-Saharan Africa, despite evidence that penile-vaginal sex cannot account for the epidemic in the region. To investigate correlates of incident HIV infection in Calabar, Nigeria, we surveyed clients at voluntary HIV counselling and testing centres. Participating clients who tested multiple times were generally similar to those testing only once in terms of demographic characteristics, sexual and blood exposures and HIV prevalence. Blood exposures were common. Serial testers had a 10% annual incidence of HIV infection. Seroconverters and seronegative serial testers were similar on most demographic characteristics and sexual exposures. However, seroconverters were more likely than seronegatives to report blood exposures during the test interval, both for most specific exposures as well as summary measures of blood exposures. In particular, seroconverters were substantially more likely to report one of a set of blood exposures that cannot be explained as a consequence of unprotected vaginal sex or of health care for symptoms of HIV infection (adjusted odds ratio = 6.6, 95% confidence interval = 1.2-38). The study design we used is an inexpensive approach for describing the local epidemiology of HIV transmission and can also serve as the foundation for more definitive investigations that employ contact tracing and sequencing of HIV DNA.

Unresolved issues in the management of ulcers of the foot in diabetes.

Management of diabetic foot ulcers presents a major clinical challenge. The response to treatment is often poor and the outcome disappointing, while the costs are high for both healthcare providers and the patient. In such circumstances, it is essential that management should be based on firm evidence and follow consensus. In the case of the diabetic foot, however, clinical practice can vary widely. It is for these reasons that the International Working Group on the Diabetic Foot has published guidelines for adoption worldwide. The Group has now also completed a series of non-systematic and systematic reviews on the subjects of soft tissue infection, osteomyelitis, offloading and other interventions designed to promote ulcer healing. The current article collates the results of this work in order to demonstrate the extent and quality of the evidence which is available in these areas. In general, the available scientific evidence is thin, leaving many issues unresolved. Although the complex nature of diabetic foot disease presents particular difficulties in the design of robust clinical trials, and the absence of published evidence to support the use of an intervention does not always mean that the intervention is ineffective, there is a clear need for more research in the area. Evidence from sound clinical studies is urgently needed to guide consensus and to underpin clinical practice. It is only in this way that patients suffering with these frequently neglected complications of diabetes can be offered the best hope for a favourable outcome, at the least cost.

Outcome of directly observed therapy short course (DOTS) regimen in a rural community of the Nigerian Niger Delta.

BACKGROUND: [corrected] The objective of this retrospective study was to evaluate the outcome of directly observed therapy short course (DOTS) application in a Nigerian rural community. METHODS: A retrospective study of all the records of DOTS at the centre from January 2001 to December 2005 was compiled and features such as: age, gender, drugs used, and outcome of treatment (defaulted, cured, died, or developed multidrug resistant-TB) were considered. Also the different personnel and infrastructure at the centre for the programme were also assessed. Results were analysed using Epi Info 6 statistical software, and P values < 0.05 were considered significant. RESULTS: Two hundred and seventy four (274) cases of pulmonary TB were registered at the centre during the study period, consisting of 100 (36.5%) females and 174 (63.5%) males with a statistically significant gender difference (P<0.001). The age range with the highest number of pulmonary tuberculosis cases was 31-40 years (24.8%; n=68), and the age range with the lowest number was 71 years and above (1.1%; n=3). Treatment outcome showed that 84.7% (n=232) completed treatment with cure; 2.5% (n=7) developed multidrug resistance at completion of treatment; 5.5% (n=15) defaulted; 3.3% (n=9) died in the course of treatment, and treatment in 11 people was still ongoing. CONCLUSION: The outcome of DOTS in the present study was impressive, and the programme should be extended to other rural communities; however, more efforts should be made towards the tracing of defaulters.

The impact of laboratory closing times on delay of adequate therapy in blood stream infections.

BACKGROUND: Patients with bloodstream infections need early adequate antimicrobial treatment to reduce mortality. This raises the question of timing and logistics. How important is the time of day when a culture is flagged positive to the processing of blood cultures and optimisation of antimicrobial therapy? METHODS: We performed a retrospective study assessing the time delay of a positive blood culture result during and after office hours and its impact on adequate antimicrobial therapy. Process duration from the moment of culture positivity to Gram stain completion was compared at different timepoints during the day in a medium-sized hospital with an offsite microbiological laboratory. RESULTS: Ninety-four patients with positive, noncontaminated blood cultures were included. Sixty-six patients (70%) received adequate empirical therapy; this increased to 76 cases (82%) and to 88 cases (95%) after analysis of Gram stain results and complete determination, respectively (p < 0.05 for all comparisons). Median duration from culture positivity to Gram stain completion (including offsite culture transport) increased from a median of four to 12 hours if time of cultures turned positive after office hours (p < 0.05), irrespective of the adequacy of empirical coverage. This also resulted in a median 12-hour delay for the complete process from time of culture positivity to administration of the antimicrobial drug (p < 0.05). CONCLUSION: Processing blood cultures after office hours is often deferred, which can lead to a delay in adequate antimicrobial therapy for patients with bloodstream infections.

Hormonal control of substrate cycling in humans.

Recent studies have established the existence of substrate cycles in humans, but factors regulating the rate of cycling have not been identified. We have therefore investigated the acute response of glucose/glucose-6P-glucose (glucose) and triglyceride/fatty acid (TG/FA) substrate cycling to the infusion of epinephrine (0.03 microgram/kg.min) and glucagon. The response to a high dose glucagon infusion (2 micrograms/kg.min) was tested, as well as the response to a low dose infusion (5 ng/kg.min), with and without the simultaneous infusion of somatostatin (0.1 microgram/kg.min) and insulin (0.1 mU/kg.min). Additionally, the response to chronic prednisone (50 mg/d) was evaluated, both alone and during glucagon (low dose) and epinephrine infusion. Finally, the response to hyperglycemia, with insulin and glucagon held constant by somatostatin infusion and constant replacement of glucagon and insulin at basal rates, was investigated. Glucose cycling was calculated as the difference between the rate of appearance (Ra) of glucose as determined using 2-d1- and 6,6-d2-glucose as tracers. TG/FA cycling was calculated by first determining the Ra glycerol with d5-glycerol and the Ra FFA with [1-13C]palmitate, then subtracting Ra FFA from three times Ra glycerol. The results indicate that glucagon stimulates glucose cycling, and this stimulatory effect is augmented when the insulin response to glucagon infusion is blocked. Glucagon had minimal effect on TG/FA cycling. In contrast, epinephrine stimulated TG/FA cycling, but affected glucose cycling minimally. Prednisone had no direct effect on either glucose or TG/FA cycling, but blunted the stimulatory effect of glucagon on glucose cycling. Hyperglycemia, per se, had no direct effect on glucose or TG/FA cycling. Calculations revealed that stimulation of TG/FA cycling theoretically amplified the sensitivity of control of fatty acid flux, but no such amplification was evident as a result of the stimulation of glucose cycling by glucagon.