Disposable plasmonic plastic SERS sensor.

The 'Klarite™' SERS sensor platform consisting of an array of gold coated inverted square pyramids patterned onto a silicon substrate has become the industry standard over the last decade, providing highly reproducible SERS signals. In this paper, we report successful transfer from silicon to plastic base platform of an optimized SERS substrate design which provides 8 times improvement in sensitivity for a Benzenethiol test molecule compared to standard production Klarite. Transfer is achieved using roll-to-roll and sheet-level nanoimprint fabrication techniques. The new generation plastic SERS sensors provide the added benefit of cheap low cost mass-manufacture, and easy disposal. The plastic replicated SERS sensors are shown to provide ~10(7) enhancement factor with good reproducibility (5%).

Mechanism of enhanced insulin sensitivity in athletes. Increased blood flow, muscle glucose transport protein (GLUT-4) concentration, and glycogen synthase activity.

UNLABELLED: We examined the mechanisms of enhanced insulin sensitivity in 9 male healthy athletes (age, 25 +/- 1 yr; maximal aerobic power [VO2max], 57.6 +/- 1.0 ml/kg per min) as compared with 10 sedentary control subjects (age, 28 +/- 2 yr; VO2max, 44.1 +/- 2.3 ml/kg per min). In the athletes, whole body glucose disposal (240-min insulin clamp) was 32% (P < 0.01) and nonoxidative glucose disposal (indirect calorimetry) was 62% higher (P < 0.01) than in the controls. Muscle glycogen content increased by 39% in the athletes (P < 0.05) but did not change in the controls during insulin clamp. VO2max correlated with whole body (r = 0.60, P < 0.01) and nonoxidative glucose disposal (r = 0.64, P < 0.001). In the athletes forearm blood flow was 64% greater (P < 0.05) than in the controls, whereas their muscle capillary density was normal. Basal blood flow was related to VO2max (r = 0.63, P < 0.05) and glucose disposal during insulin infusion (r = 0.65, P < 0.05). The forearm glucose uptake in the athletes was increased by 3.3-fold (P < 0.01) in the basal state and by 73% (P < 0.05) during insulin infusion. Muscle glucose transport protein (GLUT-4) concentration was 93% greater in the athletes than controls (P < 0.01) and it was related to VO2max (r = 0.61, P < 0.01) and to whole body glucose disposal (r = 0.60, P < 0.01). Muscle glycogen synthase activity was 33% greater in the athletes than in the controls (P < 0.05), and the basal glycogen synthase fractional activity was closely related to blood flow (r = 0.88, P < 0.001). IN CONCLUSION: (a) athletes are characterized by enhanced muscle blood flow and glucose uptake. (b) The cellular mechanisms of glucose uptake are increased GLUT-4 protein content, glycogen synthase activity, and glucose storage as glycogen. (c) A close correlation between glycogen synthase fractional activity and blood flow suggests that they are causally related in promoting glucose disposal.

Long-term results after treatment of basal cell carcinoma of the eyelid in South-Western Finland.

PURPOSE: Basal cell carcinoma (BCC) is the most common skin cancer of the eyelid, showing an increasing incidence in the white population. The authors studied the clinical characteristics and the treatment results of BCC of the eyelid in southwestern Finland during 1977-1997. METHODS: The authors reviewed the case records of 191 patients with BCC of the eyelids treated at the Turku University Eye Clinic during 1977-1997. The mean follow-up period after the treatment was 8.6+/-5.2 years. RESULTS: The 191 patients had altogether 194 BCC tumors of the eyelid with the mean diameter of the tumor being smaller than 10 mm in 77.3% of cases. Of the 194 BCC tumors of the eyelid 16.0% showed recurrence, and the recurrence rate of all surgically treated tumors was 13.7%. In this study 61 patients (31.9%) developed other malignancies than the BCC of the eyelid including 28 patients (14.7 %) with carcinoma in other locations than skin. CONCLUSIONS: Incompletely removed BCCs of the eyelid showed only 18.9% recurrence rate during the follow-up time. On the other hand, BCCs of the eyelid should not be underestimated because of the rather high total recurrence rate. The frequency of 31.9% of other malignancies than BCC of the eyelid is remarkably high and requires special attention from the ophthalmologist taking care of the patient with BCC of the eyelid.

Improved glycaemia in type 1 diabetes results in decreased levels of soluble adhesion molecules with no change in serum adiponectin or most acute phase proteins.

AIMS: To investigate how reduction of hyperglycaemia affects acute phase serum proteins in poorly controlled type 1 diabetic patients. METHODS: 24 patients (age 31.7 +/- 2.0 years, HbA1c 9.3 +/- 0.2%, BMI 24.2 +/- 0.7 kg/m2, diabetes duration 15.3 +/- 1.7 years) participated in the study. The treatment was optimised for 16 weeks. Blood samples were taken at baseline and at the end of the study. 16 healthy age- and BMI-matched subjects were chosen for a control group. RESULTS: At baseline, the patients had higher C-reactive protein (CRP) (1.09, median [range 0.24-18.82] mg/l vs. 0.66 [0.18-2.46] mg/l, p < 0.02), mean adiponectin (16.06 +/- 1.31 vs. 8.85 +/- 0.93 mg/l, p < 0.001), ceruloplasmin (306 +/- 16.1 vs. 205.4 +/- 5.5 mg/l, p < 0.001), fibrinogen (3.41 +/- 0.26 vs. 2.38 +/- 0.07 g/l, p < 0.001), soluble intercellular adhesion molecule-1 (sICAM-1) (255.4 +/- 10.3 vs. 194 +/- 10.6 microg/l, p < 0.001), soluble vascular adhesion molecule-1 (sVCAM-1) (533.4 +/- 21.8 vs. 422.9 +/- 20.7 microg/l, p < 0.01) and interleukin-6 (2.89 +/- 0.49 vs. 1.35 +/- 0.30 ng/l, p < 0.01) concentrations than the controls. During intensified treatment, HbA1c decreased (to 8.5 +/- 0.2%, p < 0.001). This resulted in reduced sE-selectin (from 44.6 +/- 2.6 to 38.8 +/- 2.6 microg/l, p < 0.01), alpha-1-acid-glycoprotein (A1GP) (from 622.9 +/- 47.9 to 525.7 +/- 27.9 mg/l, p < 0.01), sICAM-1 (from 255.4 +/- 10.3 to 240.8 +/- 9.1 microg/l, p < 0.05) and IL-6 (from 2.9 +/- 0.5 to 2.1 +/- 0.4 ng/l, p < 0.01). Serum amyloid A (SAA) and CRP did not change 12.00 (0.7-222.0) vs. 12.00 (1.6-277.0) mg/l for SAA and 1.09 (0.24-18.82) vs. 1.09 (0.18-23.08) mg/l for CRP, baseline vs. treatment, respectively. CONCLUSIONS: Poorly controlled type 1 diabetic patients have increased values of adiponectin, CRP, ceruloplasmin, fibrinogen, sICAM-1, sVCAM-1 and IL-6. Reduction of hyperglycaemia results in decreased sE-selectin, A1GP, sICAM-1 and IL6, while other inflammatory factors including CRP, SAA and adiponectin are not affected.

Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP).

BACKGROUND: We showed previously that repeated dietary counseling during the first 3 years of life reduces the concentration of serum nonfasting cholesterol. We have now extended the study to children 5 years of age and analyzed fasting blood samples, enabling LDL cholesterol calculations for the first time. METHODS AND RESULTS: Families of 7-month-old infants (n=1062) were randomized to a control group (n=522) or an intervention group (n=540) that received individualized dietary counseling with the aims of a fat intake of 30% to 35% of daily energy, a saturated/monounsaturated/polyunsaturated fatty acid ratio of 1:1:1, and a cholesterol intake of <200 mg/d. Nutrient intakes were studied biannually, nonfasting serum lipid values were studied annually, and fasting values were studied at 5 years of age. The intervention children always had lower intakes of saturated fat and cholesterol than the control children. The intervention boys had 0.39 mmol/L (P:<0.0001) lower mean serum cholesterol values than the control boys between 13 and 60 months of age, but among girls, the difference was of marginal significance (0.15 mmol/L, P:=0.052). Five-year-old intervention boys had 9% lower mean serum LDL cholesterol concentrations than the control boys (P:=0.0002; 95% CI, -0.39 to -0.12 mmol/L), whereas no difference was observed in girls. In both sexes, serum triglyceride concentrations were similar in the 2 groups. CONCLUSIONS: The restriction of saturated fat and cholesterol intake by repeated, individualized dietary counseling since infancy resulted in lower serum total and LDL cholesterol concentrations at 5 years of age. However, the effect was significant only in boys.

Athletes with IDDM exhibit impaired metabolic control and increased lipid utilization with no increase in insulin sensitivity.

Physical exercise is traditionally recommended to diabetic patients as part of their treatment. Although healthy athletes exhibit enhanced skeletal muscle insulin sensitivity, the metabolic effects of vigorous training in patients with insulin-dependent diabetes mellitus (IDDM) are not known. This study was designed to examine the effects of competitive sports on fuel homeostasis and insulin sensitivity in athletes with IDDM. We studied 11 athletes and 12 matched sedentary men with IDDM. In each subject, we measured glycemic control, insulin-stimulated glucose uptake in the whole body and forearm, rates of glucose and lipid oxidation, and muscle glycogen, glycogen synthase, and glucose transport protein (GLUT4) concentrations. The athletes had higher VO2max (52 +/- 1 vs. 42 +/- 1 ml.kg-1.min-1, P < 0.001) and HbA1c levels (8.4 +/- 0.4 vs. 7.2 +/- 0.2%, P < 0.05) than sedentary patients, but took smaller insulin doses (41 +/- 3 vs. 53 +/- 3 U/day, P < 0.05). The insulin-stimulated rates of whole-body and forearm glucose uptake and glucose oxidation were similar in the two groups, whereas both energy expenditure and lipid oxidation were increased in the athletes. Lipid oxidation correlated inversely with glycogen synthase activity. The mean glucose arterialized venous blood-deep venous blood (A-V) difference during the insulin infusion (60-240 min) correlated with the whole-body glucose disposal throughout the insulin infusion (after 60 min, r > 0.73, P < 0.001 for all 30-min periods). This association is accounted for by the relationship between glucose A-V difference and nonoxidative glucose disposal. Muscle glycogen and GLUT4 protein contents were not different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Lispro Mix25 insulin as premeal therapy in type 2 diabetic patients.

OBJECTIVE: Insulin Mix25 is a new premixed insulin analog containing 25% insulin lispro and 75% neutral protamine lispro (NPL) suspension (NPL insulin). The aim of the study was to compare serum glucose and insulin responses after breakfast in type 2 diabetic patients who received Mix25, premixed regular/NPH (30%/70%), or NPH insulin before the meal. RESEARCH DESIGN AND METHODS: We studied 22 type 2 diabetic patients of age 62 +/- 1 years, BMI 30 +/- 1 kg/m2, duration of diabetes 15 +/- 2 years, duration of insulin therapy 6 +/- 1 years, insulin dose 65 +/- 6 U/day, and HbA1c 7.9 +/- 0.2%. Ten healthy individuals (age 56 +/- 1 years, BMI 28 +/- 1 kg/m2) served as control subjects. Each patient (except healthy subjects, who were studied once each) was studied three times in a double-blind, randomized fashion. After an overnight fast, the patients received 36 +/- 4 U of test insulin. Ten minutes after insulin injection, the patients ingested a breakfast meal (512 kcal, 60% carbohydrate, 20% fat, and 20% protein), identical in all studies. Blood samples were taken before and at 10- to 30-min intervals for 240 min after the breakfast meal. RESULTS: The peak rise in serum glucose was lower after Mix25 (76 +/- 7 mg/dl) than after 30/70 (94 +/- 5 mg/dl, P < 0.05) or NPH (113 +/- 4 mg/dl, P < 0.005) insulin. The incremental area under the serum glucose curve was 36% smaller after Mix25 than after 30/70 (P < 0.01) and 56% smaller than after NPH (P < 0.005) insulin. The peak rise in serum insulin concentration was higher after Mix25 (103 +/- 18 mU/l) than after 30/70 (87 +/- 13 mU/l, P < 0.05) or NPH (62 +/- 12 mU/l, P < 0.01) insulin. The incremental area under the serum insulin curve was higher after Mix25 than after 30/70 during the first 2-3 h (P < 0.02), but the difference disappeared by the end of the 4-h follow-up period. After Mix25 injection, there was an inverse correlation between the glucose response to a meal and insulin dose (r = -0.56, P < 0.01) or the incremental area under the serum insulin curve (r = -0.39, P < 0.05). No such correlations were observed with the other insulins. CONCLUSIONS: Because of its faster initial absorption rate, the new premixed insulin analog Mix25 reduces blood glucose response to a breakfast meal in type 2 diabetic patients compared with premixed 30/70 (regular/NPH) or NPH insulin.

Long-term lisinopril therapy reduces exercise-induced albuminuria in normoalbuminuric normotensive IDDM patients.

OBJECTIVE: To study the effect of lisinopril on the exercise-induced urinary albumin excretion rate. RESEARCH DESIGN AND METHODS: A total of 26 IDDM patients with normoalbuminuria were randomized into two groups, with one group receiving placebo (n = 13, age 36 +/- 3 years, BMI 24.5 +/- 1.1 kg/m2) and the other group receiving an average of 15 mg lisinopril daily (n = 13, age 34 +/- 2 years, BMI 24.4 +/- 0.9 kg/m2). Overnight and exercise-induced urinary albumin excretion rate was measured at baseline and after 1 and 2 years of treatment. Two patients in the placebo group and none in the lisinopril group developed microalbuminuria. RESULTS: In the lisinopril group, the exercise-induced urinary albumin excretion rate diminished 46% after the 1st year (P = 0.059) and 66% (P < 0.01) after the 2nd year. However, it remained unchanged in the control group. Systolic blood pressure (sBP) and diastolic blood pressure (dBP) were similar at baseline and after 1 year, but at 2 years, sBP was 13 mmHg lower (P = 0.03) and dBP was 9 mmHg lower (P = 0.052) in the lisinopril group as compared with the control group. The dBP decreased significantly at 1 and 2 years in the lisinopril group, while there was no significant change in the sBP. In the whole group at baseline, the overnight albumin excretion rate correlated with HbA1c (r = 0.50, P < 0.01) and the duration of diabetes (r = 0.39, P < 0.05), and sBP correlated with both the overnight (r = 0.42, P < 0.05) and the exercise-induced (r = 0.48, P < 0.05) albumin excretion rate. CONCLUSIONS: Glycemic control and blood pressure are directly related to the overnight albumin excretion rate also in normotensive normoalbuminuric IDDM patients. Lisinopril treatment reduces the exercise-induced urinary albumin excretion rate in such patients. These data suggest a protective effect of lisinopril against the development of microalbuminuria.

Bone mineral density in patients with type 1 and type 2 diabetes.

OBJECTIVE: To assess the effect of type 1 and type 2 diabetes and insulin treatment on bone mineral density (BMD) in middle-aged and elderly men and women. RESEARCH DESIGN AND METHODS: We measured BMD and evaluated known determinants of osteoporosis in 56 type 1 and 68 type 2 diabetic patients and 498 nondiabetic community control subjects. All patients, aged 52-72 years, developed diabetes after the age of 30 years (i.e., after achievement of peak bone mass) and were treated with insulin. BMD was measured at the proximal femur with dual-energy X-ray absorptiometry. RESULTS: Among both sexes, BMD values were significantly lower in type 1 diabetic patients than in type 2 diabetic patients or the control subjects. When adjusted for age and BMI, the differences between type 1 diabetic patients and control subjects remained essentially unchanged in both sexes, whereas the differences between type 1 and type 2 diabetic subjects were significant only in men. After further adjustments for confounding factors, the average BMD values were still lower in type 1 diabetic subjects than in type 2 diabetic subjects although with lesser significance. Past low-energy fractures were more common in type 1 diabetic women than in type 2 diabetic women. CONCLUSIONS: The lower BMD in type 1 versus type 2 diabetic patients and control subjects probably results from more rapid bone loss after the onset of type 1 diabetes. This cannot be explained by insulin treatment, which was prescribed for both types of patients. Because the causes of low BMD in type 1 diabetes are unknown, these patients should be evaluated for the risk of osteoporosis and related fractures and offered appropriate preventive measures.

Seven years of remission in a type I diabetic patient.

OBJECTIVE: To analyze factors contributing to a long-term remission in a patient with type I diabetes. RESEARCH DESIGN AND METHODS: The patient was treated with cyclosporin for 16 mo after a short duration of symptoms. During the 7-yr follow-up, we tracked his glycemic control, oral glucose tolerance, insulin sensitivity, endogenous insulin secretion, and beta-cell immunology. The results are compared with those of matched diabetic patients and healthy control subjects. RESULTS: Insulin therapy was discontinued after 5 wk. Thereafter the patient had normal fasting and home blood glucose concentrations and near-normal HbA1c without insulin therapy for 7 yr. During this period, he maintained islet cell antibodies, although his basal and glucagon-stimulated C-peptide concentrations were normal. He participated in active physical training and had an insulin sensitivity higher than in sedentary control subjects or trained diabetic patients and equal to that in healthy athletes. His oral glucose tolerance decreased gradually and became diabetic during the last 3 yr. CONCLUSIONS: In this patient, an early start of cyclosporin therapy probably contributed to the maintenance of endogenous insulin secretion, and insulin sensitivity was high because of physical training. Consequently, the patient was able to maintain normoglycemia without exogenous insulin therapy for 7 yr.

Clinical testing of thermally stimulated cardiovascular oscillations in man.

STUDY OBJECTIVE: The study assessed the physiological validity of an automatic thermal stimulation method to induce synchronised oscillations in the neural cardiovascular control system. DESIGN: Automatic alternating rhythmic warm and cool immersion of different skin areas of 18 males was done at different frequencies and water temperatures. The neurally mediated responses to the periodic thermal stimulation were measured from skin blood flow and heart rate and compared to those of a sham stimulation. Respiration was monitored for control purposes. The reproducibility of the stimulation and responses was examined. SUBJECTS: 18 young males volunteered for the study. MEASUREMENTS AND MAIN RESULTS: The water bath method produced reproducible thermal stimulation and responses of skin blood flow and heart rate. Rhythmic thermal stimulation at 0.013-0.096 Hz synchronised the oscillations of the forearm skin blood flow when the thermal stimulus amplitude exceeded 10 degrees C. The increase in the stimulus amplitude or enlargement of the stimulus area did not further increase the oscillatory response of skin blood flow. Sham stimulation or mean temperature of the periodic thermal stimulation in the range 23-33 degrees C did not influence the oscillations of skin blood flow. Local cooling of the stimulated lower legs attenuated the response of skin blood flow. Both thermal stimulation and sham stimulation affected heart rate, but no stable synchronisation of the periodic heart rate variability was found at supine rest. Thermal stimulation of the sitting subjects' forearm instead of legs increased the synchronisation of the periodic heart rate variability. CONCLUSIONS: The response of skin blood flow agreed with the theory of the thermal entrainment. In a supine man, both thermal stimulation and non-specific central nervous influences induced significant and reproducible interactions with periodic heart rate variability and respiration.

A non-invasive method for testing neural circulatory control in man.

Exaggerated cardiovascular responsiveness is common in young men and may cause non-specific symptoms and poor performance. Conventional autonomic function tests are not clinically useful. We have therefore designed a thermal entrainment method to evaluate sympathetic and parasympathetic cardiovascular function in subjects with dystonic symptoms and orthostatic intolerance. Oscillations of thermal gradient in the skin were produced by standardised periodic stimulation of the lower part of the arm with warm and cool water. Vasomotor activity of the skin induced oscillations of arterial blood pressure which were thought to be regulated by sympathetic and parasympathetic heart rate control and by oscillation of the sympathetically controlled peripheral vascular resistance. We tested the method in subjects with cardiovascular symptoms (n = 7) and controls (n = 7). At supine rest, the frequency response of the heart rate variability to the thermal stimulation at frequencies of 0.01, 0.02, 0.03 and 0.1 Hz was significantly different (p = 0.008) between symptomatic subjects and controls. The gain of the heart rate control was increased to 0.03 Hz [-1.3(SEM 0.5) dB v -3.8(0.8) dB, p = 0.068] and decreased at 0.1 Hz [-3.9(1.1) dB v -1.5(0.6) dB, p = 0.076] in the test group compared to the control group. At stimulus frequencies of less than 0.03 Hz the individual overall heart rate variability of the subjects with symptoms stayed below the mean control value, at 60(6) ms v 79(15) ms, p = 0.16. The cutaneous temperature oscillations at the site of stimulation, frequency response of the oscillations of the skin blood flow and respiration to the thermal stimulation, and mean heart rate were similar in the both groups. The results show that this thermal entrainment method quantifies the increased sympathetic and decreased parasympathetic cardiac control of subjects with dystonic symptoms.

R2R-printed inverted OPV modules--towards arbitrary patterned designs.

We describe the fabrication of roll-to-roll (R2R) printed organic photovoltaic (OPV) modules using gravure printing and rotary screen-printing processes. These two-dimensional printing techniques are differentiating factors from coated OPVs enabling the direct patterning of arbitrarily shaped and sized features into visual shapes and, increasing the freedom to connect the cells in modules. The inverted OPV structures comprise five layers that are either printed or patterned in an R2R printing process. We examined the rheological properties of the inks used and their relationship with the printability, the compatibility between the processed inks, and the morphology of the R2R-printed layers. We also evaluate the dimensional accuracy of the printed pattern, which is an important consideration in designing arbitrarily-shaped OPV structures. The photoactive layer and top electrode exhibited excellent cross-dimensional accuracy corresponding to the designed width. The transparent electron transport layer extended 300 µm beyond the designed values, whereas the hole transport layer shrank 100 µm. We also examined the repeatability of the R2R fabrication process when the active area of the module varied from 32.2 cm(2) to 96.5 cm(2). A thorough layer-by-layer optimization of the R2R printing processes resulted in realization of R2R-printed 96.5 cm(2) sized modules with a maximum power conversion efficiency of 2.1% (mean 1.8%) processed with high functionality.

Pharmacokinetics of clodronate in renal failure.

The pharmacokinetic parameters describing the fate of one intravenous clodronate (disodium dichloromethane diphosphonate) dose was studied in 24 normal subjects and in 24 patients with different degrees of renal insufficiency. The aim of the study was to derive data for adjustment of dosage in relation to renal function. Disodium clodronate in serum and urine samples was analyzed by capillary gas chromatography with mass-selective detection. The renal clearance (CLR) of clodronate was highly dependent on renal function and declined successively with declining glomerular filtration rate (GFR). Plasma clearance (CLP) declined, too, but to a lesser degree than CLR. The impairment of renal function resulted in decreased cumulative urinary elimination of clodronate and increased total areas under the serum concentration-time curve (AUC0-infinity). Hence, as the renal elimination of clodronate diminishes with decreasing GFR, there is a related retention of the substance. As a result of the present study, the following dosages are recommended: creatinine clearance (CLCr) from 50 to 80 ml/minute, 75-100% of normal dose; CLCr 12-50 ml/minute, 50-75% of normal dose; and ClCr < 12 ml/minute, 50% of normal dose. The results must be interpreted with caution in patients with malignancy and severe skeletal disease, in whom the nonrenal clearance may vary markedly.

Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients.

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, insulin, and testosterone in 15 men with insulin-dependent diabetes mellitus (IDDM; age, 29 +/- 2 yr; body mass index, 22.7 +/- 0.5 kg/m2; body fat, 9.5 +/- 1.0%; insulin dose, 44 +/- 4 U/day; hemoglobin A1c, 8.1 +/- 0.3%; diabetes duration, 12.7 +/- 2.0 yr) and 15 healthy control subjects (age, 27 +/- 1 yr; body mass index, 22.6 +/- 0.4 kg/m2; body fat, 9.6 +/- 0.5%) in the fasting state. In addition, the effect of a 4-h euglycemic hyperinsulinemia (approximately 600 pmol/L) on the plasma leptin concentration was determined. The fasting leptin concentration was negatively correlated to plasma testosterone (r = -0.55; P < 0.05) in IDDM patients. The fasting plasma leptin level rose 25% in healthy subjects (from 1.0 +/- 0.2 to 1.3 +/- 0.3 ng/mL; P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained unchanged (2.7 +/- 0.2 vs. 2.7 +/- 0.2 ng/mL) during hyperinsulinemia. We reached the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is resistant to the acute effect of insulin. 2) Serum testosterone may contribute to the regulation of leptin synthesis in IDDM patients.

Selegiline in the treatment of daily fluctuations in disability of parkinsonian patients with long-term levodopa treatment.

In order to evaluate in a double-blind manner the therapeutic efficacy of selegiline in the treatment of late-phase Parkinson's disease, 19 patients with end-of-dose type fluctuations were randomized for a double-blind cross-over trial receiving either selegiline 10 mg or placebo. Each period lasted 12 weeks. During a two week prestudy period the dose of levodopa was titrated to optimal levels. The disability was evaluated using the Columbia University Disability Scale (CUDS). The patients kept a daily diary to monitor closely the frequency and severity of their fluctuations and the side-effects of treatment. Their parkinsonian disability and all main symptoms improved significantly during selegiline treatment. The mean duration of action of a levodopa dose was significantly longer and there was significantly less daily end-of-dose and early morning akinesia during selegiline treatment. The side-effects were similar in both treatments. This double-blind study confirms the findings of earlier open studies that selegiline potentiates and prolongs the therapeutic effects of levodopa and thus its use is particularly beneficial in patients with end-of-dose type fluctuations in disability.

Selegiline as primary treatment in early phase Parkinson's disease--an interim report.

We are carrying out a double-blind parallel trial comparing the effect of selegiline monotherapy and placebo in de novo parkinsonian patients. Fifty-six patients (28 in both groups) are included in the trial. This interim analysis reports the results of the first 52 evaluable patients who have had at least one follow-up visit after entering the trial. The efficacy of treatment was assessed using the Columbia University Rating Scale, the North-Western University Disability Scale and the Webster Rating Scale and followed until the addition of levodopa therapy became necessary. The data were analysed at follow-up times of up to twelve months (34 patients evaluable at the end of the period). The overall disability scores of all the rating scales used were significantly smaller in the selegiline group than in the placebo group. Levodopa treatment had become necessary in 12 patients (46%) in the selegiline group and in 14 patients (54%) in the placebo group. The side-effects were mild and similar in both treatment groups. According to the present results selegiline monotherapy seems to have therapeutic efficacy in the early phase of Parkinson's disease. Whether selegiline is able to slow down the progression of Parkinson's disease needs further clarification.

Metabolic response to lactitol and xylitol in healthy men.

Sugar alcohols are used in food products, yet their metabolic effects in humans are poorly known. We examined plasma glucose, insulin, and C-peptide responses and changes in carbohydrate and lipid oxidation after the ingestion of 25 g lactitol, xylitol, or glucose. Eight healthy, nonobese men were studied after an overnight fast. After the ingestion of lactitol or xylitol, the rise in plasma glucose, insulin, and C-peptide concentrations was less than after the ingestion of glucose (P < 0.02), with no difference between the two polyols. With the glycemic index of glucose as 100, the indexes of xylitol and lactitol were 7 and -1, respectively. A reactive hypoglycemia was observed 3 h after glucose ingestion, but not after the ingestion of sugar alcohols. There were no significant changes in the carbohydrate or lipid oxidation as determined by indirect calorimetry after the ingestion of sugar alcohols. After glucose ingestion, the rise in carbohydrate oxidation was nearly significant (P = 0.07). In conclusion, lactitol and xylitol cause smaller changes than does glucose in plasma glucose and insulin concentrations and thermogenic response. A small hormonal response and the lack of a thermogenic effect may be beneficial when these sugar alcohols are used in food products. The small glucose and insulin responses also suggest that lactitol and xylitol are suitable components of the diet for diabetic patients.

Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study.

PURPOSE: To compare subcutaneously given molgramostim (GM-CSF) and sucralfate mouth washings to sucralfate mouth washings in prevention of radiation-induced mucositis. METHODS AND MATERIALS: Forty head and neck cancer patients were randomly assigned to use either GM-CSF and sucralfate (n = 20) or sucralfate alone (n = 20) during radiotherapy. Sucralfate was used as 1.0 g mouth washing 6 times daily after the first 10 Gy of radiotherapy, and 150-300 microg GM-CSF was given subcutaneously. The grade of radiation mucositis and blood cell counts were monitored weekly. Salivary lactoferrin was measured as a surrogate marker for oral mucositis. RESULTS: We found no significant difference between the molgramostim and the control groups in the oral mucositis grade, oral pain, use of analgesic drugs, weight loss, or survival. The median maximum neutrophil counts (median, 9.2 x 10(9)/L vs. 5.9 x 10(9)/L, p = 0.0005), eosinophil counts (median, 1.3 x 10(9)/L vs. 0.2 x 10(9)/L, p = 0.0004), and salivary lactoferrin concentrations were higher in patients who received GM-CSF. The most common toxicities in the GM-CSF plus sucralfate group were skin reactions at the GM-CSF injection site (65%), fever (30%), bone pain (25%), and nausea (15%), whereas the toxicity of sucralfate given alone was minimal. CONCLUSION: We found no evidence indicating that subcutaneously given GM-CSF reduces the severity of radiation-induced mucositis.