Effects of Lactobacillus hilgardii 4785 and Lactobacillus buchneri 40788 on the bacterial community, fermentation and aerobic stability of high-moisture corn silage.

AIMS: To evaluate the capacity of Lactobacillus hilgardii and Lactobacillus buchneri on modifying the bacterial community and improving fermentation and aerobic stability of high-moisture corn (HMC). METHODS AND RESULTS: High-moisture corn was untreated (CTR), treated with L. hilgardii (LH) or L. buchneri (LB) at 600 000 CFU per gram fresh weight, or with L. hilgardii and L. buchneri at 300 000 CFU per gram fresh weight each (LHLB), and stored for 10, 30 or 92 days. Compared to CTR, inoculated silages had higher Lactobacillaceae relative abundance, lower yeasts numbers and higher aerobic stability. Treatment with LHLB resulted in a higher acetic acid concentration than LH and higher 1,2 propanediol concentration than LB, such differences were numerically greater at 10 and 30 days but statistically greater at 92 days. At 10 days, all inoculated silages were more stable than CTR, but LHLB was even more stable than LB or LH. CONCLUSIONS: The combination of L. hilgardii and L. buchneri had a synergistic effect on yeast inhibition, leading to greater improvements in aerobic stability as early as 10 days after ensiling. SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus hilgardii, especially in combination with L. buchneri, can improve the aerobic stability of HMC after a very short period of ensiling.

Silage review: Using molecular approaches to define the microbial ecology of silage.

Ensiling of forages was recognized as a microbial-driven process as early as the late 1800s, when it was associated with the production of "sweet" or "sour" silage. Classical microbiological plating techniques defined the epiphytic microbial populations associated with fresh forage, the pivotal role of lactic acid-producing bacteria in the ensiling process, and the contribution of clostridia, bacilli, yeast, and molds to the spoilage of silage. Many of these classical studies focused on the enumeration and characterization of a limited number of microbial species that could be readily isolated on selective media. Evidence suggested that many of the members of these microbial populations were viable but unculturable, resulting in classical studies underestimating the true microbial diversity associated with ensiling. Polymerase chain reaction-based techniques, including length heterogeneity PCR, terminal RFLP, denaturing gradient gel electrophoresis, and automated ribosomal intergenic spacer analysis, were the first molecular methods used to study silage microbial communities. Further advancements in whole comparative genomic, metagenomic, and metatranscriptomic sequencing have or are in the process of superseding these methods, enabling microbial communities during ensiling to be defined with a degree of detail that is impossible using classical microbiology. These methods have identified new microbial species in silage, as well as characterized shifts in microbial communities with forage type and composition, ensiling method, and in response to aerobic exposure. Strain- and species-specific primers have been used to track the persistence and contribution of silage inoculants to the ensiling process and the role of specific species of yeast and fungi in silage spoilage. Sampling and the methods used to isolate genetic materials for further molecular analysis can have a profound effect on results. Primer selection for PCR amplification and the presence of inhibitors can also lead to biases in the interpretation of sequence data. Bioinformatic analyses are reliant on the integrity and presence of sequence data within established databases and can be subject to low taxonomic resolution. Despite these limitations, advancements in molecular biology are poised to revolutionize our current understanding of the microbial ecology of silage.

Silage review: Unique challenges of silages made in hot and cold regions.

Silage making can be conveniently divided into field, ensiling, storage, and feed-out phases. In all of these stages, controllable and uncontrollable components can affect silage quality. For instance, silages produced in hot or cold regions are strongly influenced by uncontrollable climate-related factors. In hot regions, crops for silage are influenced by (1) high temperatures negatively affecting corn yield (whole-crop and grain) and nutritive value, (2) butyric and alcoholic fermentations in warm-season grasses (Panicum, Brachiaria, and Pennisetum genera) and sugarcane, respectively, and (3) accelerated aerobic deterioration of silages. Ensiling expertise and economic factors that limit mechanization also impair silage production and utilization in hot environments. In cold regions, a short and cool growing season often limits the use of crops sensitive to cool temperature, such as corn. The fermentation triggered by epiphytic and inoculated microorganisms can also be functionally impaired at lower temperature. Although the use of silage inoculants has increased in Northern Europe, acid-based additives are still a good option in difficult weather conditions to ensure good fermentation quality, nutritive value, and high intake potential of silages. Acid-based additives have enhanced the quality of round bale silage, which has become a common method of forage preservation in Northern Europe. Although all abiotic factors can affect silage quality, the ambient temperature is a factor that influences all stages of silage making from production in the field to utilization at the feed bunk. This review identifies challenges and obstacles to producing silages under hot and cold conditions and discusses strategies for addressing these challenges.

Silage review: Mycotoxins in silage: Occurrence, effects, prevention, and mitigation.

Ensiled forage, particularly corn silage, is an important component of dairy cow diets worldwide. Forages can be contaminated with several mycotoxins in the field pre-harvest, during storage, or after ensiling during feed-out. Exposure to dietary mycotoxins adversely affects the performance and health of livestock and can compromise human health. Several studies and surveys indicate that ruminants are often exposed to mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins, zearalenone, and many other fungal secondary metabolites, via the silage they ingest. Problems associated with mycotoxins in silage can be minimized by preventing fungal growth before and after ensiling. Proper silage management is essential to reduce mycotoxin contamination of dairy cow feeds, and certain mold-inhibiting chemical additives or microbial inoculants can also reduce the contamination levels. Several sequestering agents also can be added to diets to reduce mycotoxin levels, but their efficacy varies with the type and level of mycotoxin contamination. This article gives an overview of the types, prevalence, and levels of mycotoxin contamination in ensiled forages in different countries, and describes their adverse effects on health of ruminants, and effective prevention and mitigation strategies for dairy cow diets. Future research priorities discussed include research efforts to develop silage additives or rumen microbial innocula that degrade mycotoxins.

Effect of temperature (5-25°C) on epiphytic lactic acid bacteria populations and fermentation of whole-plant corn silage.

AIMS: The objective of this study was to investigate the effect of temperature (5-25°C) on epiphytic lactic acid bacteria (LAB) populations during 60 days of fermentation of whole-plant corn silage. METHODS AND RESULTS: Vacuum bag mini-silos of chopped whole-plant corn were incubated at five different temperatures (5, 10, 15, 20 and 25°C), according to a completely randomized design with four repetitions. The silos were opened and sampled on day 0, 1, 2, 3, 7, 28 and 60. At 20 and 25°C, Lactobacillus plantarum- and Pediococcus  pentosaceus-related operational taxonomic units (OTU) dominated the fermentation within 1 day. After 7 days, the OTU related to the heterofermentative species Lactobacillus buchneri began to appear and it eventually dominated silages incubated at these temperatures. Population dynamic of LAB at 5 and 10°C was different. At these temperatures, Leuconostoc citreum OTU was identified at the beginning of the fermentation. Thereafter, Lactobacillus sakei- and Lactobacillus curvatus-related OTU appeared and quickly prevailed. Corn silage at 15°C acted as a transition between 20-25°C and 5-10°C, in terms of LAB diversity and succession. CONCLUSION: The conditions of silage incubation temperature affect species diversity of LAB population with notable difference along the temperature gradient. Colder temperature conditions (5 and 10°C) have led to the identification of LAB species never observed in corn silage. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrated the impact of temperature gradient on the diversity and some important population shift of lactic acid bacteria communities during fermentation of corn silage.

Screening histories and contact with physicians as determinants of cervical cancer risk in Montreal, Quebec.

BACKGROUND: Cervical cancer (cca) is largely a preventable disease if women receive regular screening, which allows for the detection and treatment of preinvasive lesions before they become invasive. Having been inadequately screened is a common finding among women who develop cca. Our primary objective was to determine the Pap screening histories of women diagnosed with cca in Montreal, Quebec. Secondary objectives were to determine the characteristics of women at greatest risk of cca and to characterize the level of physician contact those women had before developing cca. METHODS: The Invasive Cervical Cancer Study, a population-based case-control study, consisted of Greater Montreal residents diagnosed with histologically confirmed cca between 1998 and 2004. Respondents to the 2003 Canadian Community Health Survey and a sample of women without cca obtained from Quebec medical billing records served as controls. RESULTS: During the period of interest, 568 women were diagnosed with cca. Immigrants and women speaking neither French nor English were at greatest risk of cca. Most of the women in the case group had been screened at least once during their lifetime (84.8%-90.4%), but they were less likely to have been screened within 3 years of diagnosis. Having received care from a family physician or a medical specialist other than a gynecologist within the 5 years before diagnosis was associated with a greater risk of cca development. CONCLUSIONS: Our findings provide evidence of the need for an organized population-based screening program. They also underscore the need for provider education to prevent missed opportunities for cca screening when at-risk women seek medical attention.

Fatigue-independent alterations in muscle activation and effort perception during forearm exercise: role of local oxygen delivery.

The oxygen-conforming response (OCR) of skeletal muscle refers to a downregulation of muscle force for a given muscle activation when oxygen delivery (O2D) is reduced, which is rapidly reversed when O2D is restored. We tested the hypothesis that the OCR exists in voluntary human exercise and results in compensatory changes in muscle activation to maintain force output, thereby altering perception of effort. In eight men and eight women, electromyography (EMG), oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb), forearm blood flow (FBF), and task effort awareness (TEA) were measured. Participants completed two nonfatiguing rhythmic handgrip tests consisting of 5-min steady state (SS) followed by two bouts of 2-min brachial artery compression to reduce FBF by ~50% of SS (C1 and C2), separated by 2 min of no compression (NC1) and ending with 2 min of no compression (NC2). When FBF was compromised during C1, EMG/Force (1.58 ± 0.39) increased compared with SS (1.31 ± 0.33, P = 0.001). However, EMG/Force was not restored upon FBF restoration at NC1 (1.48 ± 0.38, P = 0.479), consistent with C1 evoking skeletal muscle fatigue. When FBF was compromised during C2, EMG/Force increased (1.73 ± 0.50) compared with NC1 (1.48 ± 0.38, P = 0.013). EMG/Force returned to NC1 levels during NC2 (1.50 ± 0.39, P = 0.016), consistent with an OCR in C2. TEA (SS 2.2 ± 2.3, C1 3.9 ± 2.5, NC1 3.4 ± 2.7, C2 4.6 ± 2.7, NC2 3.9 ± 2.8) mirrored changes in EMG. It is noteworthy that during the second compromise and then restoration of muscle oxygenation EMG and TEA were rapidly restored to precompromise levels. We interpreted these findings to support the existence of an OCR and its ability to rapidly modify perception of effort during voluntary exercise. NEW & NOTEWORTHY In healthy individuals, when force output is maintained during rhythmic handgrip exercise, muscle activation and perception of effort rapidly increase with compromised muscle oxygen delivery (O2D) and then return to precompromised levels when muscle O2D is restored. These findings suggest that an oxygen-conforming response (OCR) exists and is able to modify perception of effort during voluntary exercise. Therefore, similar to fatigue, an OCR may have implications for exercise tolerance.

Electron paramagnetic resonance studies of the membrane fluidity of the foodborne pathogenic psychrotroph Listeria monocytogenes.

Listeria monocytogenes is a foodborne psychrotrophic pathogen that grows at refrigeration temperatures. Previous studies of fatty acid profiles of wild-type and cold-sensitive, branched-chain fatty acid deficient mutants of L. monocytogenes suggest that the fatty acid 12-methyltetradecanoic (anteiso-C(15:0)) plays a critical role in low-temperature growth of L. monocytogenes, presumably by maintaining membrane fluidity. The fluidity of isolated cytoplasmic membranes of wild-type (SLCC53 and 10403S), and a cold-sensitive mutant (cld-1) of L. monocytogenes, grown with and without the supplementation of 2-methylbutyric acid, has been studied using a panel of hydrocarbon-based nitroxides (2N10, 3N10, 4N10, and 5N10) and spectral deconvolution and simulation methods to obtain directly the Lorentzian line widths and hence rotational correlation times (tau(c)) and motional anisotropies of the nitroxides in the fast motional region. tau(c) values over the temperature range of -7 degrees C to 50 degrees C were similar for the membranes of strains SLCC53 and 10403S grown at 10 degrees C and 30 degrees C, and for strain cld-1 grown with 2-methylbutyric acid supplementation (which restores branched-chain fatty acids) at 30 degrees C. However, strain cld-1 exhibited a threefold higher tau(c) when grown without 2-methylbutyric acid supplementation (deficient in branched-chain fatty acids) compared to strains SLCC53, 10403S, and supplemented cld-1. No evidence was seen for a clear lipid phase transition in any sample. We conclude that the fatty acid anteiso-C(15:0) imparts an essential fluidity to the L. monocytogenes membrane that permits growth at refrigeration temperatures.

Cisplatin-cyclophosphamide versus carboplatin-cyclophosphamide in advanced ovarian cancer: a randomized phase III study of the National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: Given the potential for improved tolerance, a trial was initiated to compare the toxicity and efficacy of a standard regimen of cisplatin-cyclophosphamide (75 mg/m2 and 600 mg/m2, respectively) with an experimental regimen of carboplatin-cyclophosphamide (300 mg/m2 and 600 mg/m2, respectively) in women with postoperative macroscopic residual ovarian cancer. PATIENTS AND METHODS: Between 1985 and 1989, 447 (417 eligible) patients were randomized. Treatment arms were well balanced; most patients had stage III (82%), grade 3 (54%) tumors with bulky residual (greater than 2 cm in 59%), and good performance status (Eastern Cooperative Oncology Group [ECOG] 0 or 1, 77%). Response was assessed after six 4-week cycles. RESULTS: The treatments were equally deliverable, with 76% of patients completing their allocated regimen. The reported reasons for failure to complete treatment differed; toxicity/refusal predominated on the cisplatin arm, and progressive disease predominated on the carboplatin arm (P = .0092). Cisplatin-treated patients were more likely to develop neuropathy and nephropathy, and carboplatin patients experienced myelosuppression, particularly thrombocytopenia. Efficacy was similar, with no significant differences for the cisplatin and carboplatin arms in clinical response rate (57% v 59% in those with measurable disease), pathologic response rate (52% v 54% in those suitable for relaparotomy), time to progression (median, 56 v 58 weeks), or overall survival (median, 100 weeks v 110 weeks). Time to progression and survival were predicted by residual disease size, performance status, and treatment center (with those treated at centers that accrued more patients doing better). CONCLUSION: Neither regimen is optimal in that relapse remains the norm. It may be inappropriate to expect that any single regimen can be an effective therapy for all patients with advanced ovarian cancer. Both cisplatin and carboplatin are likely to have a role in future treatment strategies.

Randomized phase II study of two schedules of topotecan in previously treated patients with ovarian cancer: a National Cancer Institute of Canada Clinical Trials Group study.

PURPOSE: As topotecan is S-phase-specific, its efficacy is likely schedule-dependent. Therefore, a randomized study using a "pick the winner" design was undertaken to compare two schedules in patients with recurrent ovarian cancer. PATIENTS AND METHODS: Patients with recurrent epithelial ovarian cancer previously treated with no more than two separate regimens of chemotherapy, one of which had to be platinum-containing, were randomized to either topotecan 1.5 mg/m2 intravenously (i.v.) over 30 minutes daily for 5 days repeated every 21 days (arm A, the standard arm), or topotecan 1.75 mg/m2 as a 24-hour infusion once a week for 4 weeks repeated every 6 weeks (arm B, the experimental arm). RESULTS: Sixty-six patients were eligible and 63 were assessable for response. The response rate in arm A was 22.6% (95% confidence interval [CI], 9.6% to 41.2%), which was significantly superior to that in arm B, 3.1% (95% CI, 0.1% to 16%) (P = .026). The regimens were not equitoxic, with 94% of patients on arm A experiencing grade 3 or 4 granulocytopenia as opposed to 52% on arm B. CONCLUSION: The weekly 24 hour infusion of topotecan at 1.75 mg/m2 was ineffective in relapsed ovarian cancer. The daily-times-five schedule remains the schedule of choice. As the regimens were not equitoxic, one cannot differentiate between an ineffective schedule and an ineffective dose as the reason for the differing response rates. However, the degree of myelotoxicity that already occurs will preclude any substantially higher dosing with the weekly regimen.

Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix.

PURPOSE: To test the hypothesis that cisplatin (CDDP) administered concurrently with standard radiotherapy (RT) would improve pelvic control and survival in patients with advanced squamous cell cancer of the cervix. PATIENTS AND METHODS: A total of 259 patients with International Federation of Gynecology and Obstetrics stage IB to IVA squamous cell cervical cancer with central disease greater-than-or-equal 5 cm or histologically confirmed pelvic lymph node involvement were randomized to receive RT (external-beam RT plus brachytherapy) plus weekly CDDP chemotherapy (40 mg/m(2)) (arm 1) or the same RT without chemotherapy (arm 2). RESULTS: A total of 253 patients were available for analysis. Median follow-up was 82 months. No significant difference was found in progression-free survival (P =.33). No significant difference in 3- and 5-year survival rates was found (69% v 66% and 62% v 58%, respectively; P =.42). The hazard ratio for survival (arm 2 to arm 1) was 1.10 (95% confidence interval, 0.75 to 1.62). CONCLUSION: This study did not show a benefit to either pelvic control or survival by adding concurrent weekly CDDP chemotherapy in a dose of 40 mg/m(2) to radical RT as given in this trial. Careful attention to RT details is important for achieving optimum outcome for patients with this disease.

Apolipoprotein A-I-containing particles and reverse cholesterol transport in IDDM.

Lipoprotein particles containing apoA-I but not apoA-II are, among high-density lipoproteins, effective protectors against atherosclerosis that act by promoting the efflux of cellular cholesterol and the reverse cholesterol transport process. Because previous studies showed that in vitro nonenzymatic glycosylation of HDL impairs HDL receptor-mediated cholesterol efflux, we isolated Lp A-I from two poorly controlled insulin-dependent diabetic patients and compared the chemical composition and ability to promote cholesterol efflux with the same particles purified from two matched nondiabetic control subjects. No differences in lipid composition or in the ability to promote cholesterol efflux from cultured adipose cells were noted between the two types of Lp A-I preparations. However, when we separated Lp A-I from diabetic subjects by degree of glycosylation, the specifically glycosylated subfractions were about 50% less effective in producing cholesterol efflux than the nonglycosylated particles.

Decreased erythrocyte membrane fluidity in poorly controlled IDDM. Influence of ketone bodies.

OBJECTIVE: To examine the factors that might alter the fluidity of erythrocyte membrane in insulin-dependent diabetes mellitus (IDDM) patients. RESEARCH DESIGN AND METHODS: The subjects were 10 health men and 30 IDDM mem: 10 with good blood glucose (BG) control (HbA1c 5.88 +/- 0.60% [mean +/- SD]), 10 with poor BG control (HbA1C 9.48 +/- 1.05%), and 10 with poor BG control and mild to moderate diabetic ketoacidosis (DKA) (HbA1C 9.12 +/-2.25%, strongly positive ketonuria 3+ and elevated plasma beta-hydroxybutyrate). Erythrocyte membrane fluidity was determined by fluorescence polarization using 6-(9-anthroyloxy stearic acid as fluorescent probe. RESULTS: Membrane fluidity was normal in the diabetic patients with good BG control but significantly lower in the two groups of patients with poor BG control than in the healthy subjects (P < 0.01). The membrane fluidity in the poor BG control groups was also lower in the patients with DKA than in those without DKA (P < 0.01). CONCLUSIONS: The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Reliability of self-monitoring of blood glucose by CSII-treated patients with type I diabetes.

The reliability of patient-generated data from self-monitoring of blood glucose (SMBG) was studied in 14 patients with type I (insulin-dependent) diabetes mellitus treated by continuous subcutaneous insulin infusion (CSII) (7 women, 7 men). The reflectance meters (Glucometer I, Ames, Elkhart, IN) used by the patients were replaced for a period of 21 days by memory-reflectance meters; patients were unaware of the memory capacity of the new meters and were instructed to continue their practice of recording the meter readings in their logbook. This study compares the data recorded in the memory-reflectance meters with those reported in the logbook. The number of SMBG measurements was different in 11 patients (differences ranging from 2 to 66). Mean glycemia was similar (8.23 +/- 0.36 mM in logbook vs. 8.49 +/- 0.48 mM in memory-reflectance meters), but both the M value and mean amplitude of glycemic excursions (MAGE) index were lower when calculated from logbook data (38 +/- 5 vs. 48 +/- 7 mM, P less than .05 and 6.91 +/- 0.43 vs. 7.72 +/- 0.52 mM, respectively; P less than .05). Overreporting (addition of phantom values in logbook) and underreporting (omission of SMBG measurements from logbook) indexes were 19 +/- 7 and 12 +/- 3%, respectively. Precision (percent of identical values in logbook and in memory-reflectance meters at the corresponding time) was 77 +/- 6.8%. The number of SMBG measurements recorded in the memory-reflectance meter was negatively correlated with glycosylated hemoglobin [HbA1c; (r = -.85, P less than .001)], whereas overreporting was positively correlated with HbA1c (r = .76, P less than .01).

Improved visual evoked potential latencies in poorly controlled diabetic patients after short-term strict metabolic control.

OBJECTIVE: To determine whether short-term strict control of blood glucose can improve abnormal visual evoked potentials (VEPs) in poorly controlled diabetic patients with no overt diabetic complications. RESEARCH DESIGN AND METHODS: VEPs (P100 wave latencies) were recorded in 12 poorly controlled diabetic patients (7 with insulin-dependent diabetes mellitus and 5 with non-insulin-dependent diabetes mellitus) before and after at least 3 days of near normoglycemia obtained by continuous subcutaneous insulin infusion (CSII). Exclusion criteria were overt diabetic neuropathy or retinopathy. The control subjects were 12 healthy subjects matched for age and sex. Fifty-two other subjects formed a reference control population. The intra-individual coefficient of variation for P100 latency was < 3%. RESULTS: The P100 latencies were longer in diabetic patients than in control subjects (means of both eyes +/- SD: 116.8 +/- 10.1 vs. 106.2 +/- 4.5 ms, P < 0.01), and 4 of the 12 diabetic patients had abnormal VEPs. After 3 days of close blood glucose control (mean blood glucose profile fell from 13.7 +/- 2.2 mmol/l to 6.8 +/- 1.2 mmol/l, P < 0.01), the mean P100 latencies were significantly shorter (112.5 +/- 7.6 ms, P < 0.01) but were still significantly longer than control values. The longer the initial P100 latency, the greater the decrease after CSII. There was no correlation between the fall in blood glucose and improvement in VEPs. CONCLUSIONS: Short-term blood glucose normalization is associated with improved P100 wave latency in uncomplicated diabetic patients. These data suggest that abnormal VEPs are partly reversible and include functional disturbances related to glucose metabolism.

The prevalence of retinopathy is similar in diabetes mellitus secondary to chronic pancreatitis with or without pancreatectomy and in idiopathic diabetes mellitus.

In a retrospective study, we compared the prevalence of retinopathy in two groups of 88 diabetic patients (84 men, 4 women) with either diabetes mellitus secondary to chronic pancreatitis (CP-DM group) or idiopathic diabetes mellitus (I-DM group). The patients of these two groups were pair-matched according to age (48.7 +/- 1.1 versus 48.8 +/- 1.0 yr in CP-DM and I-DM groups, respectively; mean +/- SEM), sex, duration of diabetes (7.96 +/- 0.56 versus 8.08 +/- 0.8 yr) and therapy (80 on insulin and 8 on oral hypoglycemic agents in each group). Retinopathy was assessed by bilateral ophthalmoscopic examination of the fundus after pupillary dilation in all 176 patients and by fluorescein angiography in 47 patients with CP-DM and 35 patients with I-DM. Forty-one percent of patients in the CP-DM group and 45.5% of patients in the I-DM group had diabetic retinopathy (P greater than 0.5). In each group, patients with retinopathy were older than patients without retinopathy (51.6 +/- 1.3 versus 46.7 +/- 1.8 yr in the CP-DM group, P less than 0.01, and 52.1 +/- 1.5 versus 46.0 +/- 1.2 yr in the ID-M group, P less than 0.01). They had diabetes of longer duration (10.9 +/- 1.0 versus 5.9 +/- 0.6 yr in the CP-DM group, P less than 0.001, and 10.5 +/- 1.0 versus 6.0 +/- 0.6 yr in the ID-M group, P less than 0.001). The prevalence of retinopathy increased parallel to the duration of diabetes in a similar way in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Visual evoked potentials in diabetic patients.

Visual evoked potentials (VEPs) were assessed in 50 adult type I (insulin-dependent) and 19 type II (noninsulin-dependent) diabetes mellitus patients and in 54 controls. P100 wave latency was significantly longer in diabetic patients (P less than .001). Twenty-eight percent of diabetic patients had P100 wave latencies above the normal range. There was no correlation between P100 latency and type or duration of diabetes mellitus, quality of metabolic control, or presence of degenerative complications. The significance of VEP abnormalities in diabetes mellitus remains speculative.

Hyperinsulinemia is related to erythrocyte phospholipid composition and membrane fluidity changes in obese nondiabetic women.

It has been suggested that changes in the properties of cell membranes are involved in an altered insulin action. However, the influence of changes in the distribution of phospholipid classes has not been explored. We investigated 69 obese nondiabetic normoglycemic women (17 patients with impaired glucose tolerance) with varying degrees of insulin sensitivity to determine the phospholipid composition and fluid state of their erythrocyte plasma membranes. The fasting plasma insulin, the homeostasis model analysis of insulin resistance (HOMA), and the integrated area under the insulin curve (AUC-I) after an oral glucose challenge were used as markers of insulin resistance. Results were divided into normal glucose tolerance (NGT) and impaired glucose tolerance. There was a positive correlation in NGT group between the membrane sphingomyelin (SM) content and the fasting plasma insulin (r = 0.523; P < 0.0001), HOMA value (r = 0.483; P < 0.0005), and AUC-I (r = 0.352; P < 0.05) and negative correlations between membrane fluidity determined with two fluorescent probes and plasma fasting insulin (r = 0.320; r = -0.365; P < 0.05) and HOMA value (r = 0.321; r = -0.382; P < 0.05). There were also correlations between SM and the three markers of insulin resistance in the impaired glucose tolerance group. There was no correlation between insulin resistance and other membrane components. Stepwise multiple regression analysis in the NGT group confirmed that the membrane SM content was an independent predictor of plasma fasting insulin, HOMA values, and AUC-I variations. Sphingomyelin could be one of the membrane parameters contributing to insulin resistance.

Comparison of metabolic deterioration between insulin analog and regular insulin after a 5-hour interruption of a continuous subcutaneous insulin infusion in type 1 diabetic patients.

An interruption of continuous sc insulin infusion (CSII) of the insulin analog lispro should result in a more rapid metabolic deterioration of type 1 diabetic patients because of its pharmacokinetic characteristics. We analyzed the metabolic changes occurring during a 5-h interruption of CSII and the 5 h after restarting the pump in 10 type 1 diabetic patients. The study was a randomized, cross-over, open label design comparing insulin analog [Lispro (LP)] and regular insulin [Velosuline (VE)]. Plasma glucose, free insulin, glucagon, betahydroxybutyrate (beta-OHB), and nonesterified fatty acids (NEFA) were measured every hour from 0700 h (time zero) to 1700 h (600 min). After stopping CSII, the plasma glucose level was significantly higher in the LP group than in the VE group (P < 0.05-0.01). The plasma free insulin level decreased significantly with the two treatments, but was significantly lower with LP than with VE (P < 0.05-0.01). Plasma NEFA increased more rapidly and was significantly higher in the LP group than in the VE group (P < 0.01-0.05). Plasma beta-OHB increased earlier with LP, but was not statistically different between the treatments. After restarting the pump, plasma glucose decreased with LP, but continued to increase with VE, and the plasma free insulin peak occurred earlier and was greater with LP than with VE (P < 0.05). Plasma NEFA and beta-OHB levels decreased significantly with the two treatments, but more dramatically with LP treatment. Thus, a short interruption of Lispro in CSII is associated with an earlier, greater metabolic deterioration, but Lispro corrected this metabolic deterioration more effectively.

Metabolic effects of a single administration of growth hormone on lipid and carbohydrate metabolism in normal-weight and obese subjects.

The effects on lipid metabolism of a single intramuscular dose of SR 29001 (0.15 U/kg body wt), a biosynthetic human growth hormone (hGH), were explored in a double-blind randomized crossover vs a placebo study of six normal-weight and six obese subjects (Quetelet Index greater than 120%). Circulating hGH concentrations reached means of 35 and 28 ng/mL in the normal-weight and obese subjects, respectively. Free fatty acids increased in both groups (p less than 0.05); increases in beta-hydroxybutyrate and acetoacetate concentrations were more moderate (NS). Plasma glucose increased significantly despite a significant increase in insulin (p less than 0.002). The lipolytic effect persisted after a standardized 950-kcal meal eaten 5 h after hGH administration. A delayed increase in somatomedin-C and decreases in blood urea and total cholesterol were also observed (p less than 0.05). Despite increased insulin secretion, biosynthetic hGH produced a significant increase of lipolysis in both groups, which was only partially suppressed by food.