Pathology of grey seals Halichoerus grypus in southwest England including pups in early rehabilitation.

Few investigations have examined the pathology of grey seals Halichoerus grypus in southwest England, where it is the most abundant marine mammal. Here, primary pathological findings are presented from 107 post-mortem examinations of grey seals in southwest England between 2013 and 2020. Over three-quarters were pups in their first year of life; the origins of the carcasses reflected the known breeding season and breeding sites of grey seals in the region. Trauma was the most common primary pathological finding (n = 49), followed by infectious disease (n = 36). Traumatic findings included fisheries-related trauma (n = 15), other acute physical traumas (n = 15) and other chronic traumas (n = 19). Infectious disease findings included respiratory infections (n = 21) and gastrointestinal infections (n = 9). There was no difference in the primary pathological findings for seals found dead or that died or were euthanased on the day they were found compared to those dying in early rehabilitation, suggesting that it is appropriate to include findings from seals in early rehabilitation in studies of wild grey seal pathology. Seals that had not been frozen before post-mortem examination were nearly twice as likely to have a primary pathological finding of infectious disease or trauma than those that had been frozen, highlighting the need, wherever possible, to avoid freezing seals prior to post-mortem examination.

Adjunctive therapy with pramlintide lowers HbA1c without concomitant weight gain and increased risk of severe hypoglycemia in patients with type 1 diabetes approaching glycemic targets.

AIMS: In long-term clinical trials in patients with type 1 diabetes spanning a wide range of HbA1c, addition of pramlintide to existing insulin regimens led to reductions in HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia event rates. Given that weight gain and increased hypoglycemia risk contribute to the difficulty of attaining HbA1c targets (<7 %), the question arose whether pramlintide could benefit patients approaching, but not reaching glycemic targets with insulin alone. To address this question, we conducted a pooled analysis from 3 long-term clinical trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. METHODS: Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately 28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin (baseline HbA1c 7.9+/-0.4 %, body weight 76.0+/-14.3 kg [mean+/-SD]) and 281 with pramlintide+insulin (baseline HbA1c 7.9+/-0.4 %, body weight 75.4+/-13.1 kg). Endpoints included placebo-corrected changes from baseline to week 26 in HbA1c, body weight, and the event rate of severe hypoglycemia. RESULTS: Adjunctive therapy with pramlintide resulted in significant reductions in HbA1c and body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment differences, respectively, both p

A Web-based diabetes care management support system.

BACKGROUND: Because of the often asymptomatic nature of diabetes and the long period between sustained hyperglycemia and observable complications, appropriate diabetes care relies on a long-term program of secondary prevention. Yet routine monitoring and screening among patients with diabetes is less than optimal. To support the provision of routine care to patients with diabetes, the Center for Health Services Research, Henry Ford Health System (Detroit), developed a Web-based Diabetes Care Management Support System (DCMSS). A nonrandomized, longitudinal study was conducted (January 1, 1998-October 31, 1999) with 13,325 health maintenance organization patients with diabetes who were aligned to 190 primary care providers practicing in 31 primary care clinics. RESULTS: Three DCMSS features--clinical practice guidelines, patient registries, and performance reports--were made available via a corporate intranet within an existing electronic medical record. The effect of DCMSS usage frequency was evaluated on the likelihood of a patient's receipt of glycated hemoglobin testing, lipid profile testing, and retinal examinations. Logistic regression models controlling for patient sociodemographic and clinical characteristics, and the testing history of the patient, the primary care physician, and the primary care clinic, were fit using generalized estimating equation methods. The more often a physician used DCMSS, the more likely his or her patients were to receive lipid profile testing (OR [odds ratio] = 1.01, 95% CI [confidence interval] = 1.01-1.02). Compared with patients of physicians who never used the system, patients of physicians who initiated 12 sessions were an estimated 19% more likely (95% CI = 7%-33%) to receive lipid profile testing. The analyses also suggested that the likelihood of a patient receiving a retinal exam was associated with system usage (OR = 1.01, 95% CI = 1.01-1.01). No relationship was found between system use and glycated hemoglobin testing. CONCLUSIONS: Computerized systems of clinical practice guidelines, patient registries, and performance feedback may help improve the rate of routine testing among patients with diabetes.

Troglitazone in combination with sulfonylurea restores glycemic control in patients with type 2 diabetes. The Troglitazone Study Group.

OBJECTIVE: To determine if the combination of troglitazone (a peroxisome proliferator-activated receptor-gamma activator) and sulfonylurea will provide efficacy not attainable by either medication alone. RESEARCH DESIGN AND METHODS: There were 552 patients inadequately controlled on maximum doses of sulfonylurea who participated in a 52-week randomized active-controlled multicenter study. Patients were randomized to micronized glyburide 12 mg q.d. (G12); troglitazone monotherapy 200, 400, or 600 mg q.d. (T200, T400, T600); or combined troglitazone and glyburide q.d. (T200/G12, T400/G12, T600/G12). Efficacy measures included HbA1c, fasting serum glucose (FSG), insulin, and C-peptide. Effects on lipids and safety were also assessed. RESULTS: Patients on T600/G12 had significantly lower mean (+/- SEM) FSG (9.3 +/- 0.4 mmol/l; 167.4 +/- 6.6 mg/dl) compared with control subjects (13.7 +/- 0.4 mmol/l; 246.5 +/- 6.8 mg/dl; P < 0.0001) and significantly lower mean HbA1c (7.79 +/- 0.2 vs. 10.58 +/- 0.18%, P < 0.0001). Significant dose-related decreases were also seen with T200/G12 and T400/G12. Among patients on T600/G12, 60% achieved HbA1c < or =8%, 42% achieved HbA1c < or =7%, and 40% achieved FSG < or =7.8 mmol/l (140 mg/dl). Fasting insulin and C-peptide decreased with all treatments. Overall, triglycerides and free fatty acids decreased, whereas HDL cholesterol increased. LDL cholesterol increased slightly, with no change in apolipoprotein B. Adverse events were similar across treatments. Hypoglycemia occurred in 3% of T600/G 12 patients compared with <1% on G12 or troglitazone monotherapy CONCLUSIONS: Patients with type 2 diabetes inadequately controlled on sulfonylurea can be effectively managed with a combination of troglitazone and sulfonylurea that is safe, well tolerated, and represents a new approach to achieving the glycemic targets recommended by the American Diabetes Association.

Insulin therapy and its shortcomings - the need for new approaches.

After its discovery in 1921, insulin rapidly became established as a treatment for insulin-requiring diabetes mellitus (Type 1 and late-stage Type 2), providing effective symptom control and significant reductions in diabetes-associated mortality. However, within 30 years of insulin's discovery, physicians were faced with a new challenge - the treatment of the long-term complications of chronic hyperglycaemia. The Diabetes Control and Complications Trial provided clear evidence of the benefits of improved glycaemic control, but also highlighted the difficulties, such as an increased risk of hypoglycaemia, of attempting to achieve this using insulin as the only pharmacological agent. We now know that the pancreatic islet hormone, amylin, is also deficient in patients with Type 1 and late-stage Type 2 diabetes. It is possible that parallel replacement of both amylin and insulin may improve glycaemic control more smoothly in patients with diabetes, with less risk of hypoglycaemia, while still reducing the long-term sequelae of chronic hyperglycaemia.

Bone loss and bone turnover in diabetes.

There have been conflicting reports about the effect of diabetes on bone density. In 1978, we studied 109 patients, 46 with type I and 63 with type II diabetes; approximately 12 years later we restudied 35 of the 66 surviving patients. In the original study, radial bone density did not differ significantly between patients with either type of diabetes but was significantly lower than in nondiabetic control subjects. In eight osteopenic patients, bone formation rate and other histological indexes of osteoblast recruitment and function were markedly depressed compared with those in nondiabetic control subjects. In patients remeasured approximately 2.5 years (41 patients) and approximately 12.5 years (35 patients) after baseline, bone loss had continued at the expected rate in patients with type I diabetes, with maintenance of the same deficit, but was slower than expected in patients with type II diabetes, such that the initial deficit had been completely corrected. In six of the eight patients who had undergone bone biopsy, one with type I and five with type II diabetes, the mean bone mineral density z-score of the spine and femoral neck approximately 12 years later was > 0 and in one subject was significantly higher than normal at both sites. Based on these data and on previous studies, we propose that in patients with diabetes, low bone formation retards bone accumulation during growth, metabolic effects of poor glycemic control lead to increased bone resorption and bone loss in young adults, and low bone turnover retards age-related bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Ongoing assessment of health status in patients with diabetes mellitus.

In 1990, the Division of Endocrinology and Metabolism of Henry Ford Hospital established an Outcomes Management data base for patients with Type I and Type II diabetes. A first cohort of 117 patients completed a baseline and 6-month follow-up assessment; a second cohort of 116 patients completed the baseline assessment. Assessment at each time point includes: the Short Form--36 Questions (SF-36) health status instrument; a set of clinical variables known as the Diabetes TyPE scale Form 2.2 abstracted from the medical record; and the physicians' ratings of patient's health status along the major dimensions of the SF-36. Success with both face-to-face and mailed administration of the SF-36 has been good, with response rates of over 85% using both methods. Comparison of patient and physician ratings of patient health status indicated a significant discrepancy on ratings of general health status, with physicians' ratings higher than those of patients themselves. "Tight" glycemic control (as measured by glycosylated hemoglobin) was associated with somewhat lower ratings on the various SF-36 dimensions for all patients in the first cohort and for Type I patients in the second cohort. However, this effect did not seem to be attributable to those features of a complex regimen used to achieve tight control, but rather reflected a complex combination of age, education level, and number of daily injections associated with achieving good control.

The why and wherefore of fructosamine.

GH and FA are useful monitors in the care of diabetic patients. For most situations, GH is the preferred test and should be routinely monitored. FA should be reserved for exceptional situations in which blood glucose control over one to two weeks must be assessed or in patients with a hemoglobinopathy. Patients with diabetes should be advised of their present GH level and the preferred goal.

Microalbuminuria in clinical practice.

Albumin excretion rate measured by new immunoassays and semiquantitative tests is advocated as a means for early detection of diabetic nephropathy. We determined albumin excretion rate in 276 patients. Albumin excretion rate was normal in 66%, within the microalbuminuric range in 27%, and within the macroproteinuric range in 7%. Significant predictors of albumin excretion rate included presence of hypertension and glycosylated hemoglobin level in type I diabetes mellitus, and years since diagnosis in type II diabetes mellitus. A semiquantitative test was deemed to be of limited diagnostic value. We conclude that testing for early diabetic nephropathy in routine clinical practice gives valuable information and that determination by a quantitative immunoassay based on a single 24-hour urine sample is preferable. The optimal frequency of screening and the levels that determine progressive renal disease have yet to be established.

An ambulatory approach to self-care of diabetes.

Managing the insulin-requiring diabetic patient in an ambulatory setting includes metabolic regulation of the diabetes and education in its self-care. Means of achieving these goals include structured group or one-on-one individualized sessions. Third party policies relating to ambulatory care are challenged and their need for fiscal support emphasized. During the coming decade, diabetic patients should 1) have access to ambulatory care programs for metabolic regulation and education in self-care, 2) expect third party support of these programs, and 3) heighten their own priorities on diabetes care to ensure quality management of their diabetes.

Capsaicin: a therapeutic option for painful diabetic neuropathy.

Fifteen patients with diabetes mellitus who had painful diabetic neuropathy (PDN) were enrolled in a double-blind study to test the safety and efficacy of capsaicin 0.075% (Axsain, Genderm, Northbrook, IL). Twelve of the 15 patients completed the eight-week study. Nine of the 12 patients reported symptomatic relief; of these nine, five used the drug and four used the vehicle. The three patients who reported no relief of symptoms applied the vehicle. Capsaicin is potentially effective when burning pain is a major symptom of PDN. The side effects of capsaicin were limited and minimal. This agent should be considered by clinicians for treatment of PDN.

Evaluation of the insulin jet injector as a potential source of infection.

In recent years jet injection of insulin has been widely used by patients with diabetes mellitus. Jet injectors may become contaminated by bacteria because of repeated use without cleaning; cleansing every 2 weeks is recommended. We investigated the occurrence of bacterial contamination by culturing jet injectors in everyday use by 19 patients with diabetes. Swabs from the interior chambers were cultured on blood agar plates. Only one of 20 cultures yielded bacterial growth, and the organism recovered was a presumed contaminant that could not be identified as any common pathogen. No study patient, nor any of more than 70 patients whom we instructed in jet injection, showed any clinical evidence of infection attributable to jet injector use. Jet injectors are unlikely to become colonized by bacteria or to cause infection in patients using them for insulin administration. The low rate of colonization may be due to the antibacterial preservatives added to commercial preparations of insulin. Additional data based on larger numbers of patients would be useful in further clarifying the risk of infection associated with jet injectors.

Motor vehicles, hypoglycemia, and diabetic drivers.

Individuals with diabetes are increasingly persuing employment in fields previously restricted as a result of the development of chronic complications. Improved glycemic control resulting from use of sophisticated insulin delivery and monitoring systems has also led to the recognition of recurrent hypoglycemia as a potential major clinical and occupational hazard. No data concerning the occupational safety of individuals with insulin-treated diabetes mellitus (ITDM) are available. We review the literature on diabetic drivers in an effort to examine the impact of certification of ITDMs as commercial drivers. In the absence of significant worldwide experience with ITDMs as commercial drivers, the discussion is necessarily based on projected accident rates derived from data on frequency of hypoglycemia. These studies are universally flawed by variable definitions of hypoglycemia, ascertainment bias, and patient selection. They do, however, provide a worst-case/best-case scenario for discussion. It is imperative that any expansion of employment opportunities for ITDMs be followed carefully with prospective studies to assess the impact on public safety.

Evaluation of a new chemical dip strip for detecting ketonemia in the emergency setting.

The utility of a new urine dipstick, Chemstrip uK, was evaluated using serum in place of urine to quantify serum ketones in 29 acutely ill patients with suspected ketosis treated in the emergency department. The serum Chemstrip uK method accurately predicted the level of ketonemia as assessed by the Acetest tablet method (r = .94; P less than .0001). There were no false-negative and no false-positive results. The use of this strip is recommended for evaluating subjects with suspected ketosis.