High incidence rate of IDDM in Sardinia. Sardinian Collaborative Group for Epidemiology of IDDM.

To provide reliable data on the incidence of IDDM in Sardinia and contribute to a better understanding of its geographical variability throughout Europe. All newly diagnosed cases of IDDM with onset less than 30 yr of age between 1 January 1989 and 31 December 1990 among residents in Sardinia were recorded. Primary ascertainment was based on notification by all Sardinian hospitals, outpatient clinics, family doctors, and pediatricians. The local IDDM patient association served as the secondary and independent source. The completeness of ascertainment was 92.8%. The annual incidence rate of IDDM (per 100,000) over the 2-yr period was 30.7 in the 0-14-yr-old age-group and 24.1 in the entire 0-29-yr-old range, respectively, with no significant differences between the two groups. Male/female ratios were 1.25 and 1.55, respectively. No significant seasonal variation in incidence was observed. Sardinia appears to have the second-highest IDDM incidence rate in Europe after Finland, and the island contradicts the generally accepted rule of a south-to-north incidence gradient.


Insulin requirements in insulin-dependent and insulin-requiring GDM women during final month of pregnancy.

To determine the significance of falling insulin requirements after the 36th wk of gestation in insulin-requiring pregnant women. Insulin requirements of women with IDDM and IRGDM were assessed from the 36th wk of pregnancy, with evaluation of maternal characteristics and fetal outcomes. In 32 pregnancies of women with IDDM, there was a 5 +/- 2% decrease in insulin requirements, and in 19 pregnancies of women with IRGDM, there was a 28 +/- 10% increase. Of the 62% of women whose insulin requirements declined, the decrement was 12 +/- 2% and was associated with longer duration of diabetes (12 +/- 2 vs. 6 +/- 1 yr, P less than 0.05) but not with age, prepregnancy BMI, weight gain, or maternal or fetal complications. Only 3 pregnancies in IRGDM women were associated with a decrease in insulin requirements. Although maternal parameters were no different from those with IDDM, infants born to women with IRGDM were smaller (3531 +/- 123 vs. 3874 +/- 94 g, P less than 0.005). Insulin requirements from the 36th wk of gestation commonly decreased in women with IDDM, associated with longer duration of diabetes but did not carry any adverse prognostic indication for the infants. Women with IRGDM experienced a continual increase in insulin requirements over the final weeks of pregnancy.


Relationship of postload plasma glucose to mortality with 19-yr follow-up. Comparison of one versus two plasma glucose measurements in the Chicago Peoples Gas Company Study.

To explore the relationship of one versus two postload plasma glucose measurements to 19-yr mortality in men in the Chicago Peoples Gas Company Study. One-hour postload plasma glucose was measured twice (1.4 yr apart, 1965-1967) for 873 nondiabetic men 34-65 yr of age. Serum cholesterol, blood pressure, height, and weight were measured. Data on smoking habits were obtained. Mortality follow-up was complete through July 1986, 19 yr after second glucose load. In prospective analyses, with each of three glucose values--first, second, and mean of first and second--coronary, cardiovascular, and all-cause age-adjusted mortality rates were higher in quintiles 3, 4, and 5 compared with quintile 1, with a significant linear trend. Multivariate analyses with glycemia as a continuous variable confirmed a positive independent association between plasma glucose and mortality endpoints with first measurement and mean of two values but not with second. With dichotomization of plasma glucose (greater than or equal to 11.2 mM [greater than or equal to 200 mg/dl]) for 30 men hyperglycemic both times, CHD and CVD death rates were significantly higher (odds ratios 2.3-2.7) compared with those for 758 men consistently nonhyperglycemic. In contrast, for those hyperglycemic once only, death rates were not significantly higher. Results of multivariate analyses were consistent with these findings. These data indicate a significant relationship of asymptomatic hyperglycemia on repeat examinations to coronary and cardiovascular mortality independent of other factors measured in the study.


C-peptide response to meal challenge in nondiabetic and diabetic adults living in Wadena, Minnesota.

The goal of the study was to provide cross-sectional descriptive data on the response of C-peptide to a vigorous meal stimulus in a population-based sample of nondiabetic adults compared with a population-based sample of adults with NIDDM. Available information is scanty, especially in subjects greater than 50 yr old. The group under study included 377 adults without previously known diabetes randomly chosen from the population of the city of Wadena, Minnesota, almost all of northern European background, and 88 adults with known diabetes. PCP was measured 90 min after ingestion of 480 ml liquid meal Ensure-Plus, which includes 95 g dextrose, 26 g protein, and 25 g fat. C-peptide also was measured in a 260-min urine collection after the meal challenge. Novo antibody M1221 was used for C-peptide assay throughout the study. Participants whose medical record indicated insulin-dependent diabetes with a history of acetone production were excluded from analyses. The distribution of UCP and PCP in this group of subjects appears very broad. Both the highest and lowest values for C-peptide were observed in individuals with diabetic glucose tolerance. The mean and median values in the nondiabetic group are higher than in previously published reports. After statistical adjustment for age, sex, BMI, and concomitant plasma glucose, participants with IGT produced significantly more C-peptide than the group with NGT (3.48 vs. 2.96 nM PCP, P less than 0.05). Participants with diabetic glucose tolerance and who were not taking insulin produced as much or more C-peptide than either the NGT or IGT groups, depending on the statistical model used for adjusting for plasma glucose. Diabetic participants who were taking insulin produced significantly lower amounts of C-peptide than any of the non-insulin-taking groups (approximately 30% of the C-peptide produced by the non-insulin-taking diabetic participants). A decline in PCP production with increasing years since diagnosis (5.7%/yr) was observed exclusively in the insulin-taking NIDDM participants. Effect modification by glucose tolerance classification was observed on the relationship between plasma glucose and PCP: PCP increased with increasing plasma glucose in NGT and IGT groups, but a nonsignificant negative relationship was exhibited in diabetic participants. The data suggest that two forms of NIDDM may exist, crudely distinguished by the clinical decision to use insulin to control blood glucose levels. The insulin-taking diabetic individuals may experience a greater likelihood of pancreatic failure, whereas non-insulin-taking diabetic individuals probably experience stable pancreatic function over the course of their disease. Longitudinal observation of the Wadena cohort will provide more insight into this possibility.


Prevalence of glucose intolerance in Asian Indians. Urban-rural difference and significance of upper body adiposity.

To evaluate the prevalence of NIDDM and IGT in the urban and rural areas in southern India. Two populations of the same ethnic background, but different socioeconomic background were chosen for this study. Nine-hundred urban people and 1038 rural subjects were studied. Fasting and 2-h post-glucose capillary blood samples after a 75 g oral glucose load (WHO criteria) were obtained in these randomly selected adults (greater than or equal to 20 yr of age). Using the WHO criteria, the prevalence of NIDDM, adjusted to the age of the respective general population, was 8.2% in the urban and 2.4% in the rural populations. The prevalence was 8.4 and 7.9%, respectively, in urban men and women, and 2.6 and 1.6% in rural men and women. The age-adjusted prevalence of IGT was 8.7 and 7.8% in the urban and rural areas, respectively. The prevalence of IGT was 8.8% in urban men and 8.3% in women; the corresponding values for rural men and women were 8.7 and 6.4%. The prevalence of NIDDM increased with age, markedly so in the urban people. The urban-rural difference was significant for NIDDM (chi 2 = 29.4, P less than 0.001) but not for IGT. In the urban population, 65% of the NIDDM patients were known cases, whereas in the rural area, the known cases accounted for only 24%. Bivariate analysis showed an association of BMI, STR, and WHR with prevalence of NIDDM plus IGT. In the multiple logistic regression analysis, age, BMI, STR, and WHR were associated significantly with glucose intolerance in the urban population, whereas only age was significant in the rural population. The best predictors of NIDDM were age, BMI, WHR, and urbanization. The study showed a high prevalence of NIDDM in the urban southern Indian population. The prevalence of NIDDM in the same ethnic group in rural areas was significantly lower. The prevalence of IGT was similar in both populations. Upper body adiposity was a significant predictor of NIDDM in this population with low rates of obesity.


Eating disorders in adolescents with IDDM. A controlled study.

To determine the prevalence of clinical eating disorders and lesser degrees of disturbed eating in adolescents with IDDM and a matched sample of nondiabetic control subjects. A cross-sectional survey of eating habits and attitudes conducted in 76 adolescents with IDDM, and age- and sex-matched nondiabetic control subjects. Eating disorder features were assessed by standardized research interview adapted for use with patients with diabetes (EDE). Glycemic control was assessed by GHb assay. Adolescent girls with IDDM were heavier than nondiabetic female control subjects and were dieting more intensively to control their shape and weight. However, clinical eating disorders were no more common among adolescent girls with IDDM than among nondiabetic control subjects. Nine percent of the IDDM girls met diagnostic criteria for an operational version of "Eating disorder not otherwise specified." Fifteen percent had omitted or reduced their dose of insulin to influence their shape and weight. Eating disorder features and insulin misuse for shape and weight control were not found in IDDM or nondiabetic boys, and these two groups did not differ in their body weight. Adolescent girls with IDDM are heavier than their nondiabetic counterparts and diet more intensively to control their shape and weight. Disordered eating habits and weight control behavior are common, but no more so in IDDM than in nondiabetic subjects. Insulin misuse for the purpose of shape and weight control is not restricted to subjects with a clinical eating disorder. Disordered eating is associated with impaired glycemic control.


Prevalence of eating disorder symptoms in preadolescent and adolescent girls with IDDM.

To assess attitudinal and behavioral symptoms of eating disorders in preadolescent and adolescent girls with IDDM and a matched sample of nondiabetic subjects, and to explore the relationship between the perceived impact of IDDM and eating disorder symptoms. All eligible IDDM patients (girls, age 8-18 yr) from the case register of the Yale Children's Diabetes Clinic were recruited for this study. Of 49 eligible patients, 46 participated in the study. Control subjects were recruited among students in several local schools; 46 girls, individually age and race-matched with IDDM patients, and group-matched by father's socioeconomic status, were included in this study. All subjects participated in an investigator-based clinical interview (EDE) and completed a self-report measure of eating-related psychopathology (EDI). IDDM subjects completed the DQOL measure to determine the perceived impact of diabetes on patients' lives. IDDM patients reported significantly more regular consumption of meals and snacks than did nondiabetic subjects. No group differences were found on measures of symptoms of eating disorders: both groups reported minimal levels of symptoms. Among adolescent IDDM patients, eating disorder symptoms were related significantly to patients' dissatisfaction with the illness and its impact on their lives. It appears that when applying stringent diagnostic procedures and matching criteria, IDDM girls do not evidence an elevated prevalence of eating disorder symptoms. However, those IDDM patients who did report symptoms may be a high-risk group for the development of an eating disorder and should be followed prospectively.


Cost-effectiveness of alternative methods for diabetic retinopathy screening.

To assess from the perspectives of a government delivery system and patients, the cost-effectiveness of the 45-degrees retinal camera compared to the standard ophthalmologist's exam and an ophthalmic exam by a physician's assistant or nurse practitioner technician, for detecting nonproliferative and proliferative diabetic retinopathy. Comparison of 45-degrees fundus photographs with and without pharmacological pupil dilation taken by technicians and interpreted by experts, direct and indirect ophthalmoscopy by ophthalmologists, and direct ophthalmoscopy by technicians with seven-field stereoscopic fundus photography (reference standard). Costs were estimated from market prices and actual resource use. The study included 352 patients attending outpatient diabetes and general-medicine clinics at VA and DOD facilities. Medical system costs per true positive were: 45-degrees photos with dilation, $295; 45-degrees photos without dilation, $378; ophthalmologist, $390; and technician, $794. Patient costs per true positive were: 45-degrees photos with dilation, $139; 45-degrees photos without dilation, $171; ophthalmologist, $306; and technician, $1009. Cost-effectiveness is sensitive to program size due to high fixed cost of the camera methods but not to prevalence. Cost-effectiveness of the technician exam is strongly affected by its sensitivity. Primary-care screening with retinal photographs through pharmacologically dilated pupils for diabetic retinopathy is an appropriate and cost-effective alternative to screening by an ophthalmologist in this setting. Ophthalmologists are scarce, primary-care physicians are extremely busy, and large clinics allow fixed equipment costs to be spread across many patients.


Diabetes is not caused by cassava toxicity. A study in a Tanzanian community.

To test the hypothesis that consumption of cassava with liberation of cyanide causes diabetes in malnourished individuals. Glucose tolerance was assessed in two rural communities in Tanzania; in one (Nyambori), the main source of calories was cassava; and in the other (Uswaa), cassava was rarely eaten. Undernutrition was prevalent in both communities. The people of Nyambori were known to have high dietary cyanide exposure for many years from consumption of insufficiently processed cassava. Of the 1435 people in Nyambori greater than or equal to 15 yr old, 1067 (74%) were surveyed, and 1429 of 1472 (97%) eligible subjects in Uswaa were surveyed. All had 75-g oral glucose tolerance tests and measurement of BMI. Plasma and urine thiocyanate and blood cyanide also were measured in some subjects. Mean +/- SD plasma and urine thiocyanate levels in Nyambori were 296 +/- 190 and 497 +/- 457 microM (n = 204), respectively, compared with 30 +/- 37 and 9 +/- 13 microM, respectively, in Uswaa (n = 92) (P less than 0.001 for all differences). The mean blood cyanide level in Nyambori was elevated (1.4 [range 0.1-30.2] microM; n = 91). The prevalence of diabetes in the cassava village (Nyambori) was 0.5% compared with 0.9% in Uswaa (NS). The prevalence of IGT was similar in the two villages in the 15- to 34- and the 34- to 54-yr-old age-groups; but in those greater than or equal to 55 yr old, IGT was higher in Nyambori (17.4 vs 7.2%, P = 0.029). Mean fasting and 2-h blood glucose levels were slightly higher in Nyambori village after adjusting for age, sex, and BMI (4.5 vs. 4.2 and 5.0 vs. 4.4 mM, respectively). High dietary cyanide exposure was not found to have had a significant effect on the prevalence of diabetes in an undernourished population in Tanzania. Cassava consumption is thus highly unlikely to be a major etiological factor in so-called MRDM, at least in East Africa.


Identifying diabetic patients at high risk for lower-extremity amputation in a primary health care setting. A prospective evaluation of simple screening criteria.

To evaluate prospectively a risk categorization scheme for lower-extremity problems that incorporates the Semmes-Weinstein 5.07 monofilament and a simple exam to stratify patients who were followed in a primary-care setting into risk groups for plantar ulceration and lower-extremity amputation. Patients with diabetes in a well-defined American-Indian population were stratified into four risk categories based on sensation status to the 5.07 monofilament, the presence of foot deformity, and a history of lower-extremity events (amputation or ulceration): category 0, sensate; category 1, insensate; category 2, insensate with deformity; and category 3, history of lower extremity events. Patients were followed prospectively for lower extremity events and changes in sensation status. We gave screening exams to 358 (88%) of 406 individuals with diabetes in the community. The distribution of patients for risk categories 0, 1, 2, and 3 was 74.3, 8.4, 4.5, and 13%, respectively. Over a 32-mo follow-up period, 41 patients developed ulcerations, and incidence rates correlated positively with increasing risk category (P less than 0.00001). All 14 amputations occurred in risk groups 2 and 3. These data suggest that the risk categorization described here may have a role in identifying patients at risk for lower extremity events who are followed in a primary-care setting.


Diabetes mellitus in Alaskan Yup'ik Eskimos and Athabascan Indians after 25 yr.

To estimate the prevalence of diabetes mellitus and overweight in two populations of Alaska Natives and to compare the results with previous data. Participants' heights, weights, and random plasma glucose levels were determined. Those with a glucose of greater than or equal to 6.72 mM received a follow-up glucose-tolerance test, interpreted by WHO criteria. Overweight was defined by National Center for Health Statistics criteria and also by criteria used in previous studies. The subjects were Eskimo and Athabascan residents greater than or equal to 40 yr of age in 15 villages in southwestern Alaska. Diabetes prevalence was 4.7% for Eskimos and 10.0% for Indians. Among Eskimo men and women, the prevalence of overweight was 34 and 56%, respectively, among Indian men and women, it was 29 and 55%, respectively. Comparisons with past data indicate that the prevalence of diabetes has increased from 1.7% in 1962 for Eskimos and 1.8% in 1969 for Indians. The prevalence of diabetes appears to have increased among Eskimos and Indians in Alaska. Overweight appears to be a significant problem in both groups.


Growth of children before onset of diabetes.

To examine the growth of children before the onset of diabetes. Heights before diagnosis, expressed as SDS, of each diabetic child identified from the diabetes register and of two age- and sex-matched control subjects were obtained from records of routine examinations performed at 3.5, 6, 11, and 13 yr. The heights of their siblings, with control subjects, also were obtained. Diabetic children were considerably taller than control subjects before diagnosis (0-1 yr before diagnosis SDS 0.82 +/- 0.26 vs. 0.16 +/- 0.14, P less than 0.05, n = 24; 1-2 yr before diagnosis SDS 1.02 +/- 0.17 vs. 0.16 +/- 0.14, P less than 0.001, n = 30; 2-3 yr before diagnosis SDS 0.97 +/- 0.23 vs. 0.04 +/- 0.20, P less than 0.005, n = 16). At more than 3 yr before diagnosis, the diabetic children were not significantly taller than control subjects (SDS 0.8 +/- 0.2 vs. 0.27 +/- 0.13, respectively; n = 33). The siblings of the diabetic children were no taller than control subjects. Diabetic children, but not their siblings, were taller than control subjects before diagnosis, suggesting growth-inducing metabolic changes may precede the onset of clinical diabetes by at least 3 yr.


Increased plasma endothelin in NIDDM patients with retinopathy.

To elucidate the significance of ET in diabetic microvascular disease. We determined plasma levels of ir-ET-1 in 25 NIDDM patients without hypertension and/or renal dysfunction. The plasma levels of ir-ET-1 in NIDDM patients with simple (n = 8) and proliferative (n = 8) retinopathy were 0.58 +/- 0.04 pM and 0.60 +/- 0.04 pM, respectively, which were significantly higher than those in normal, nondiabetic subjects (0.24 +/- 0.02 pM [n = 31]) and NIDDM patients without retinopathy (0.30 +/- 0.05 pM [n = 9]). These results suggest that plasma ET-1 is related to diabetic microvascular disease.


Eating disorders and IDDM. A problematic association.

IDDM and eating disorders are common conditions in young women. Whether a specific association exists between these two disorders remains controversial. Some studies have suggested an increased incidence of eating disorders in young women with IDDM, whereas others have not detected such an increase. These differences may be attributable, at least in part, to methodological issues in study design, measurement tools, and relatively small sample sizes. Whether the prevalence of eating disorders in IDDM is increased will be resolved only by larger studies that use standardized diagnostic interviews. We suspect that certain aspects of IDDM and its management may trigger the expression of an eating disorder in susceptible individuals. Required dietary restraint and weight gain related to diabetes management are the factors most likely to be implicated. Eating disorders are relatively common in young women with IDDM and may contribute to impaired metabolic control with hypoglycemia and DKA, and to long-term microvascular complications of diabetes. Omission or reduction of required insulin, an extremely common means of weight control in these young women, is likely an important factor in this regard. Further research is required to determine more precisely the relationship between IDDM and eating disorders, and the effects of eating disorders on metabolic control and chronic complications of IDDM.


Stress and diabetes mellitus.

Stress is a potential contributor to chronic hyperglycemia in diabetes. Stress has long been shown to have major effects on metabolic activity. Energy mobilization is a primary result of the fight or flight response. Stress stimulates the release of various hormones, which can result in elevated blood glucose levels. Although this is of adaptive importance in a healthy organism, in diabetes, as a result of the relative or absolute lack of insulin, stress-induced increases in glucose cannot be metabolized properly. Furthermore, regulation of these stress hormones may be abnormal in diabetes. However, evidence characterizing the effects of stress in type I diabetes is contradictory. Although some retrospective human studies have suggested that stress can precipitate type I diabetes, animal studies have shown that stressors of various kinds can precipitate--or prevent--various experimental models of the disease. Human studies have shown that stress can stimulate hyperglycemia, hypoglycemia, or have no affect at all on glycemic status in established diabetes. Much of this confusion may be attributable to the presence of autonomic neuropathy, common in type I diabetes. In contrast, more consistent evidence supports the role of stress in type II diabetes. Although human studies on the role of stress in the onset and course of type II diabetes are few, a large body of animal study supports the notion that stress reliably produces hyperglycemia in this form of the disease. Furthermore, there is mounting evidence of autonomic contributions to the pathophysiology of this condition in both animals and humans.


Evaluating diabetes education. Are we measuring the most important outcomes?

This article reviews the published literature on diabetes education evaluations and makes recommendations for outcome measures to be used in future research. We conclude that program evaluations to date have focused too narrowly on assessing knowledge and GHb outcomes to the exclusion of other important variables. To reflect the changing emphasis and conceptual basis of diabetes education, we recommend that future evaluations do the following: 1) report on the program's target population, recruitment methods, and representativeness of participants; 2) collect measures of self-efficacy and patient-provider interaction; 3) include quality of life and patient-functioning outcomes; and 4) use more standardized and objective measures of diabetes management behaviors. We close by providing practical examples of feasible collection measures for most settings and references to studies that have done so.


Central retinal vein occlusion in young people.

In a study performed on 20 subjects with central retinal vein occlusion (CRVO) aged 40 years or less we found the ischemic form in 20%. Disc edema was a common finding at the onset, while macular edema was less frequently seen. Systemic or ocular disorders that could be related with the development of the CRVO were often found; a patient was affected with myasthenia gravis and another with Sturge-Weber syndrome: these two diseases were not previously reported in association with CRVO. In only two of the 11 patients followed-up the visual acuity improved. The visual prognosis in CRVO of young people is often poor; the more frequent cause of the reduced visual acuity is chronic cystoid macular edema.


Cyclosporine effects on optic nerve and retinal vasculitis in Behçet's disease.

In a prospective, open clinical trial, we studied long-term effects of cyclosporine (CsA) on the optic nerve and retinal vasculitis in 14 Behçet's disease patients. Patients were treated with CsA and corticosteroids for a mean period of 42 months, with a range of 36 to 52 months. They received an initial CsA dosage of 7 mg/kg/day for three days, followed by 5 mg/kg/day, and prednisone 1 mg/kg/day for three to five days, tapered to 0.4 mg/kg/day. CsA was tapered when clinical response was noted. Improvement occurred in visual acuity and visual field defects secondary to papillitis, optic neuritis, macular neuroretinitis, and retinal phlebitis, but not with retinal arteritis. Despite a 12/14 (85%) exacerbation rate, no permanent liver or renal lab tests abnormalities were noted. Intermittent, low-dose CsA therapy may be considered in treatment of acute retinal and optic nerve vasculitis assisted with Behçet's disease.


Steady-state accommodation and ocular biometry in late-onset myopia.

The steady-state accommodative responses of emmetropes and late-onset myopes was measured for an array of numbers located at -1, -3 and -5 dioptres using an objective infra-red optometer. Responses were compared for passive (reading numbers) and active (adding numbers) conditions. For the passive condition, the late-onset myopes showed a significantly lower accommodative response than the emmetropic group. No significant differences were found between the two groups for the active condition. Ocular biometric characteristics were also measured in emmetropes, late-onset myopes and early-onset myopes using keratometry and ultrasonography. No significant differences in corneal curvature, anterior chamber depth and crystalline lens thickness were found between the groups. Late-onset myopes exhibited significantly deeper vitreous chambers than emmetropes, which more than accounted for the difference in refractive error between the two refractive groups. We conclude that, while significant differences exist in the accommodative responses of late-onset myopes and emmetropes, late-onset myopia is due predominantly to elongation of the vitreous chamber.


Postcataract against-the-rule astigmatism after phacoemulsification procedure. Characteristic changes over time.

To further determine whether postoperative astigmatism is related to the amount of preoperative astigmatism, we analyzed two types of against-the-rule (AR) astigmatism induced by phacoemulsification and aspiration (PEA) procedures. The operations all utilized 10-0 polyester (Mersilene) in double running fashion for the closure of the corneoscleral incisions. The induction and spontaneous regression of several types of astigmatism were analyzed over 6 months. Surgery was all done by one surgeon, with the same surgical procedure and the same number of sutures. In postoperative AR astigmatism less than 0.7 D at 6 months, although the amount of the astigmatism 1 week postoperatively was remarkably increased (2.66 +/- 0.17 D), postoperative astigmatism was decreased 6 months following surgery. On the other hand, in postoperative AR astigmatism greater than 1.5 D at 6 months, the power of the astigmatism 1 week postoperatively (2.12 +/- 0.13 D) was not much higher than the preoperative level (1.38 +/- 0.08 D), but tended to continue increasing even 6 months after surgery. There was no difference in the power of astigmatism between 1 and 3 months postoperatively. The eyes with preoperative astigmatism (e.g. 1.38 +/- 0.08 D) and especially preoperative AR astigmatism (e.g. 1.60 +/- 0.11 D), showed an increase of their astigmatism after the PEA procedure. We discussed some risk factors which may induce greater postoperative AR astigmatism.


Postoperative necrotizing sclerokeratitis.

The postoperative necrotizing sclerokeratitis is a rare condition occurring shortly after surgical procedures, mainly following cataract extractions. After several exacerbations and remissions spontaneous scleral perforation may occur. In the described case the conservative treatment/topical antibiotics, corticosteroids/failed, therefore the damaged scleral surface was covered with lyophilized dura and the condition came to a standstill.


Visual evoked cortical potentials from transient dark and bright stimuli. Selective 'on' and 'off-pathway' testing?

The superior hemifields of five normal left eyes were stimulated by novel equal and opposite contrast pattern onset stimuli which were generated on a cathode ray tube. Patterns consisted of 144 discs, each subtending 60 min arc at the viewing distance of 40 cm and were separated by a distance equal to their diameter. Equal and opposite light changes were created by presenting the disc patterns with different luminance values on a uniform constant background (20 cd/m2). Transient visual evoked cortical potentials to the appearance and disappearance of the patterns were recorded separately and analysed. Significant amplitude differences between the responses to bright and dark stimuli were observed with light increment responses being 36-53% larger than the light decrement responses for pattern on-set and 54-80% larger for pattern off-set respectively. This finding is attributed to the difference in the input to the ON and OFF Parallel Pathways which are known to carry light increment and decrement information respectively, as well as differences in the metabolic and discharge rates of these pathways.


Effect of morphological abnormalities on blood retinal barrier permeability in diabetic retinopathy.

The morphological base for the impaired function of the blood retinal barrier was studied in 50 eyes of 10 insulin dependent and 21 non-insulin dependent patients with various levels of diabetic retinopathy. The permeability of the blood retinal barrier (PBRB) was determined by vitreous fluorophotometry with correction for autofluorescence, lens transmission and non-protein bound plasma fluorescein concentration. Morphological abnormalities of diabetic retinopathy assessed by fundus photography and fluorescein angiography were individually scored on a decimal scale and related to the PBRB by multiple regression analysis. The PBRB was not correlated to morphological abnormalities of non-proliferative retinopathy [(1) microaneurysms, (2) hard exudates, (3) soft exudates, (4) intraretinal hemorrhages, (5) fluorescein leakage, and (6) capillary closure, p greater than 0.3]. The PBRB was correlated to morphological abnormalities of (pre)proliferative retinopathy [(1) intraretinal microvascular abnormalities (SIRMA) and (2) new vessels (Sneo): PBRB = A+B.SIRMA + C.Sneo with PBRB in nm/sec, A = 1.5 +/- 0.5, B = 0.9 +/- 0.2 and C = 1.7 +/- 0.4, R2 = 0.65, p less than 0.0001]. It can be concluded that the increased blood retinal barrier permeability in diabetic patients is mainly due to (pre)proliferative abnormalities and not to non-proliferative abnormalities.


Some characteristics of saccadic eye movements in children of primary school age.

The characteristics of saccadic eye movements have been extensively studied in adults; researches have also been devoted to the saccades of preschool age children. On the contrary, for primary school-age children no data exist; we investigate the eye movements (recorded utilizing an infrared technique) of six children 7 to 11 years old. The main results indicate that the values of some parameters (for example the saccadic latency and duration) are in the same range as the values of the correspondent parameters in adults, while the values of other parameters (in particular peak velocity and mean velocity/peak velocity ratio) are distinctly different from the ones measured in adult subjects.


The current management of herpetic eye disease.

Herpes simplex disciform keratitis is a difficult condition. The general feeling is that it is an immune disease, mediated by the virus, possibly located in the endothelial cells. It is frequently combined with inflammation in the trabecular meshwork and with uveitis. There is some controversy in relation to treatment and it has been suggested that anti-virals will control herpetic disciform keratitis, particularly if the patient has never had steroids previously. The authors of this paper have, in the past, published data which showed that Acyclovir, with corticosteroid, was necessary in the management of disciform keratitis. The data suggested that Acyclovir on its own was not effective. It remained to be answered whether Acyclovir on its own would be effective in patients who never had steroids for any reason previously. This paper demonstrates clearly that it is necessary, irrespective of whether patients have had steroids in the past or not, to combine corticosteroids with Acyclovir in the management of herpetic disciform keratitis. Acyclovir, on its own, is shown to be ineffective. It has also been suggested that Acyclovir is non-toxic. In a general way this is true, but the authors suggest that Acyclovir ointment does produce a punctate keratitis in patients with tear film disease, and that oral Acyclovir is preferable in such patients.


Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys.

Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.


Comparison of subcutaneously administered soluble insulin and des-(B26-B30)-insulin-B25-amide in rabbit, pig and healthy man.

Subcutaneous injections of soluble human insulin and of the monomeric insulin analogue des-(B26-B30)-insulin-B25-amide were given to fasted rabbits, pigs and healthy man. The time course of blood glucose decline and the rate of appearance of the hormones in the peripheral circulation were studied for doses of 0.35 and 0.7 nmol/kg. In rabbits an identical time course with early glucose nadirs between 45 and 60 min and hormone peaks at about 20 min were observed for both hormones. Similar results were obtained for insulin and the analogue in pigs. When injected into humans, slightly earlier peaks of the analogue at 30 to 45 min were measured compared to insulin peaks at 60 min. In addition, a trend towards faster decline in blood glucose could be demonstrated after analogue injection. In contrast to monomeric insulin analogues produced by recombinant DNA technology, s.c. injections of des-(B26-B30)-insulin-B25-amide do not appear to meet mealtime insulin requirements better than soluble insulin.


The dawn phenomenon and diabetes control in treated NIDDM and IDDM patients.

The effect of glycaemic control on the early morning plasma glucose rise, 'the dawn phenomenon', was assessed in two matching diabetic patient groups each comprising five NIDDM and two IDDM patients per group, who were otherwise considered to be in poor (HbA1 = 11.2 +/- 0.6%) or good (HbA1 = 7.6 +/- 0.2%) glycaemic control. Hourly plasma concentrations of glucose, insulin, glucagon, cortisol, and growth hormone were measured between 03.00 and 09.00 h. In all the poorly controlled diabetic patients the mean rise in plasma glucose between 06.00-08.00 and 03.00 h was greater than or equal to 1.0 mmol/l. In contrast, the plasma glucose increment was less than 1.0 mmol/l in the well controlled diabetics. The overnight mean insulin levels in the poor and well controlled patient groups were 19.3 +/- 0.5 and 25.0 +/- 0.6 mU/l (P less than 0.001) respectively. Glucagon, cortisol, and growth hormone levels in the early morning showed no significant differences between the two groups. The decline in plasma insulin from 03.00 to 08.00 h and mean cortisol level between 03.00 and 06.00 h were both significantly correlated with the increase in plasma glucose between 03.00 and 08.00 h. We concluded that an increase of 1.0 mmol/l or more in plasma glucose during the early morning is of clinical importance.


Profound vasoconstrictive effect of cigarette smoking in diabetics with autonomic neuropathy.

Changes in leg skin temperature during and after cigarette smoking were examined in 25 diabetics with autonomic neuropathy (au-neuropathy) (mean age 52 +/- 2 years) and 23 without (mean age 49 +/- 2 years), and 15 normal controls (mean age 49 +/- 2 years) using a Thermoviewer JTG 3300. All subjects were habitual smokers. Japanese Seven Star cigarettes (each containing 1.2 mg nicotine) were used for the test. Tender brand cigarettes (0.3 mg) were used additionally to compare the effect of nicotine content on the results. The smoking-stimulated thermographic pattern in the control group was rather flat, with a slight decrease in temperature followed by a slight increase before returning to the baseline level 15-20 min after smoking. The frequency of the typical temperature decreasing pattern, characterized by a profound decrease and gradual return to the baseline level in about 1 h, was significantly higher in the diabetic group than in the control group (33/48 vs 1/15; P less than 0.005). A comparison of the two diabetic subgroups revealed that the frequency was considerably higher in the subgroup with au-neuropathy (23/25 vs 10/23). These results suggest that au-neuropathy affects smoking-induced vasoconstriction in diabetic subjects. The maximum temperature decreases recorded were 1.5 +/- 2.0 and 2.69 +/- 0.24 degrees C in the controls and diabetics with au-neuropathy, respectively. The effect of Tender cigarettes with a low nicotine content was much weaker than that of Seven Star, which further suggests that smoking-induced vasoconstriction was also nicotine-dependent.


Retrospective analysis of daily glucose profile in type 1 diabetic patients with continuous subcutaneous insulin infusion (CSII).

A retrospective analysis of blood glucose control was performed in 17 type 1 diabetic patients who regularly monitored their blood glucose concentration by visual strips over a period of 3-83 months. Analysis was performed by a patient management software loaded on a personal computer. In this cohort of patients the average daily blood glucose reading was 1.6 +/- 0.3. Blood glucose readings were collected more frequently following meal ingestion (40.3%) than in the post-absorptive state (24.6%; P less than 0.05). Blood glucose concentration fluctuated from a basal level of 146 +/- 5 mg/dl to 167 +/- 4 mg/dl in the post-prandial phases with an average daily value of 156 +/- 2 mg/dl. Blood glucose values below 80 mg/dl were evenly distributed throughout the day, while hyperglycemia (greater than 300 mg/dl) occurred more commonly after meals (42%). Daily blood glucose was higher during weekends (164 +/- 5 mg/dl) than during weekdays (155 +/- 2 mg/dl; P less than 0.05). A weak correlation was found between the number of blood glucose readings/day and daily blood glucose level. These results suggest that long-term maintenance of satisfactory metabolic control is attainable in type 1 diabetic patients and that this is mainly dependent upon subject self awareness.


Is the reuse of needles for insulin injection systems associated with a higher risk of cutaneous complications?

Twenty diabetic patients participated in a study to assess if multiple use of needles for insulin injection systems (Pens) is safe under normal daily conditions. The previous mean duration of Pen therapy was 16.3 months. During this time, the 20 patients carried out altogether more than 33,000 injections without any sign of local infection despite needle reuse. Patients were told to use needles if possible for 1, 3, 6, 9, and 12 injections before bacteriological assessment. Bacteriological investigation of these needles showed no contamination, except with one needle used three times, which was colonized with coagulase negative Staphylococcus. In contrast, half of the needles' plastic ground points which touched the skin were contaminated. No signs of infection were observed at the injection sites throughout the study. We conclude that, based on the bacteriostatic effects of commercially formulated insulin and on the siliconisation of needles' surfaces, bacterial growth is sufficiently prevented. Therefore, we can recommend the reuse of pen needles as a simple, safe and cost-beneficial procedure.


An algorithm for tight glycaemic control in diabetic infarct survivors.

An algorithm has been developed to provide predictable control of blood glucose for 48 h following acute myocardial infarction. In 29 diabetic patients intravenous infusion of soluble insulin was started upon admission to hospital and the rate adjusted hourly on the basis of bedside capillary glucose estimations. Insulin infusion rates related to glycaemia were higher in obese patients and those with severe cardiac failure. For all patients mean admission glucose levels were reduced from 18.3 +/- 5.9 mmol l-1 to 9.1 +/- 3.3 mmol l-1 at 4 h and to 8.8 +/- 2.5 mmol l-1 at 6 h. Mean glucose concentrations for 48 h after admission were 8.2 +/- 1.3 mmol l-1 for all patients. Admission glucose levels were slightly higher in patients with severe, compared to those without or mild, cardiac failure (P less than 0.1), but levels over the following 48 h were similar. Doubling insulin infusion rates before meals did not achieve tighter glycaemic control. Hypoglycaemia (glucose less than 3 mmol l-1) occurred on 11 occasions in six patients; only two episodes were symptomatic and only two episodes occurred when the insulin rates were doubled before meals. This algorithm produced tighter glycaemic control than previously published protocols, particularly in patients with severe cardiac failure. Hypoglycaemia is uncommon and the algorithm easy to administer by nursing staff.


The relationship between the development and progression of microalbuminuria and arterial blood pressure in type 1 (insulin-dependent) diabetes mellitus.

to investigate the association between urinary albumin excretion and arterial blood pressure in type 1 (insulin-dependent) diabetes. urinary albumin excretion and blood pressures were followed prospectively for a mean period of 26 months (range 18-29 months) in 46 young type 1 (insulin-dependent) diabetic subjects without overt nephropathy. Supine blood pressures (BP) were measured by a single observer using a random zero sphygmomanometer. Albumin excretion was assessed at baseline by a timed clinic excretion rate (AER; microalbuminuria = AER greater than 33 micrograms/min), and at follow-up in at least two urine specimens by the albumin/creatinine (A/Cr) ratio (micro-albuminuria = A/Cr greater than 3.7 mg/mmol). 39 subjects initially had normal AERs. Seven had developed microalbuminuria at follow-up: their mean BP rose from 114 +/- 13/62 +/- 13 to 119 +/- 7/77 +/- 5 mmHg (for diastolic BP, P less than 0.05), while there was no change in the mean BP in the remaining 32 patients. A rise in diastolic BP of greater than 10 mmHg occurred in five of the seven subjects who developed microalbuminuria, and in only seven of 32 who did not (P = 0.02). In the seven patients in whom microalbuminuria persisted (n = 3) or progressed to overt proteinuria (n = 4), BP increased from 123 +/- 12/70 +/- 14 to 139 +/- 12/88 +/- 10 mmHg (P less than 0.02 for both). this study has shown that BP is normal before the onset of microalbuminuria, and that a rise in diastolic BP accompanies the development or progression of microalbuminuria. The rate of rise in BP may be more important than the absolute level in defining 'hypertension' in young diabetic patients with microalbuminuria.


Possible participation of a prostaglandin E1 analogue in the aggravation of diabetic nephropathy.

A relation between the progression of diabetic nephropathy and glomerular hyperfiltration has been speculated. We describe two cases of non-insulin-dependent diabetic males aged 55 and 59 years in whom diabetic nephropathy was aggravated during the administration of limaprost, a a prostaglandin E1 analogue with a vasodilatory action. We also observed a short-term effect of limaprost on renal hemodynamics in three cases with diabetic nephropathy. In case 1, one year after limaprost administration the serum albumin level fell from 3.6 to 2.6 g/dl and the serum creatinine level rose from 1.0 to 1.6 mg/dl. In case 2, 9 months after limaprost administration the serum albumin level fell from 3.6 to 2.9 g/dl and the serum creatinine level rose from 1.8 to 2.3 mg/dl. In the latter stages of limaprost administration, the downslopes of reciprocal serum creatinine against time appeared to be augmented in the two cases. After the 3-day administration of limaprost, the peripheral and renal blood flows, and the glomerular filtration rate (GFR) were observed to rise, but the filtration fraction (FF) and urinary protein output were elevated. Keeping in mind the pre-existing renal damage, the increases in GFR and FF suggested acceleration of compensatory glomerular hyperfiltration in less damaged surviving glomeruli. The sustained acceleration of hyperfiltration with long-term administration of limaprost as an exogenous vasodilatory prostaglandin was assumed to eventuate in the aggravation of diabetic nephropathy. Attention should be paid to drugs which increase GFR in patients with established diabetic nephropathy.


A comparison of the relationships of the glucose tolerance test and the glycated haemoglobin assay with diabetic vascular disease in the community. The Islington Diabetes Survey.

We have compared the relationships of fasting and 2 h blood-glucose during a 75 g oral glucose tolerance test, and those of an affinity chromatography assay of glycated haemoglobin, with the presence of vascular complications of diabetes mellitus in 223 subjects without known diabetes aged over 40 years selected from a community screening study population. The subjects included 15 (6.9%) with newly diagnosed diabetes and 52 (24.1%) with impaired glucose tolerance. Employing receiver operating characteristic analysis, the tests were similar in their relationship with three cases of retinopathy, 19 of microalbuminuria and six of peripheral neuropathy. The prevalence of coronary heart disease, defined as angina, myocardial infarction, or electrocardiographic changes of ischaemia, increased linearly across all four quartiles of both 2 h blood glucose and glycated haemoglobin concentration, but using logistic regression analysis, 2 h blood glucose was a better predictor of coronary heart disease than glycated haemoglobin. Receiver operating characteristic analysis also showed that 2 h blood glucose generally performed better than any of four assays of glycated haemoglobin in classifying those subjects with coronary heart disease.


Influence of sympatho-adrenal system on insulin sensitivity using the euglycemic clamp technique.

The aim of the present study was to further investigate the role of the adrenergic system on insulin action using the euglycemic clamp technique. Whole-body glucose metabolism (GM) was calculated as the glucose infusion rate for maintaining euglycemia under insulin infusion and used as an indicator of insulin sensitivity. Euglycemic clamps were performed in adrenodemedullated, epinephrine-treated, phentolamine-treated (alpha-blockade), propranolol-treated (beta-blockade), and epinephrine plus phentolamine and/or propranolol-treated rats. The following results were obtained at an insulin level of approximately 80 mU/l. GM in adrenodemedullated rats (13.97 +/- 0.98 mg/kg/min) was significantly higher than that of the control rats (10.26 +/- 0.50 mg/kg/min, P less than 0.01). GM in epinephrine-treated rats (1.7 mg/kg body weight/h) was 2.12 +/- 0.49 mg/kg/min (P less than 0.001 vs. control). Dose-response curves for phentolamine and propranolol established maximally effective doses (3.0 mg and 12 mg/kg body weight/h, respectively). Using these doses, GM in epinephrine plus phentolamine-treated rats (4.90 +/- 0.39 mg/kg/min) was significantly higher than that of epinephrine alone and GM in epinephrine and propranolol-treated rats (4.49 +/- 0.47 mg/kg/min) was also significantly higher than that of the epinephrine alone. GM in the epinephrine plus both propranolol and phentolamine (5.94 +/- 0.45 mg/kg/min) was significantly higher than that of the epinephrine alone, but not different from either treatment alone and was not additive. Neither phentolamine alone (9.48 +/- 1.45 mg/kg/min), propranolol alone (10.36 +/- 0.55 mg/kg/min) or the combination of blockades (11.14 +/- 0.65 mg/kg/min) had any effect on GM.(ABSTRACT TRUNCATED AT 250 WORDS)


An aid for insulin needle destruction for people with failing eyesight.

Patients with diabetic retinopathy and failing eyesight have problems in cutting off the needle after insulin injection. We have developed a new aid for attachment to a Becton Dickinson Destruclip needle cutter to simplify needle destruction and make safer handling possible, and studied its effectiveness. The performance time of 10 healthy blindfolded subjects to destroy a needle was compared with and without the aid. The risk of needlestick was also compared. When no aid was used, the time to destroy a needle was on an average: first trial 54 s, second trial 33 s, and third trial 11 s, while with the aid the time was on an average: first trial 16 s, second trial 7 s, and third trial 6 s; thus, the use of the aid shortened the time. Furthermore, without the aid, the frequency of needlestick injury was 1 in 15. With the aid it never occurred. This shows that the new aid for the needle cutter is effective and reduces related injuries.


Segmental gut transit in diabetes mellitus: effect of cisapride.

Gut transit using radiopaque markers was assessed in 5 healthy subjects and 24 diabetic patients. In the diabetics, various parameters including duration of the disease and diabetic complications, such as neuropathy, retinopathy and nephropathy, were determined, and the relationships between gut transit times and these complications were evaluated. The effect of cisapride on gut transit was studied in 10 diabetic patients. Large intestinal, descending colon, distal colon, and whole gut transit times were delayed in diabetics with autonomic neuropathy compared to controls and to diabetics without autonomic neuropathy (P less than 0.01). There was no difference in proximal colon transit times among them. An inverse correlation was observed between CVRR and the transit times for descending colon, distal colon, large intestine and whole gut. Large intestinal and whole-gut transit times were delayed in diabetics with retinopathy or with nephropathy compared to diabetics without those complications (P less than 0.01). In the diabetics, oral administration of 7.5 mg/day of cisapride for 2 weeks significantly accelerated descending colon transit (P less than 0.05) and partially accelerated distal colon, large intestinal and whole-gut transit. It is concluded that diabetics with autonomic neuropathy have delayed transits for the whole gut and that this finding is apparent to some extent in the distal colon but not in the proximal colon. Chronic oral administration of cisapride, a gastrointestinal prokinetic drug, was effective to improve these gastrointestinal motility disorders in diabetics with autonomic neuropathy.


Audit of multiple insulin injection regimens in a large outpatient diabetic population.

One hundred out-patients treated by multiple insulin injection regimens underwent clinical audit by retrospective analysis of their case-notes. Patients had been on multiple insulin injection therapy (MIIT) for 1.0-4.5 years (median, 3.6 years) and had had diabetes for 2 months-33 years (median, 8.7 years) at the time of starting pen therapy. Median daily insulin dose per patient did not differ significantly following stabilisation on MIIT or at latest follow-up. The median glycated haemoglobin did not change during each of the 4 years of follow-up. During the year prior to commencing MIIT the patients showed no significant alteration in body weight. Patients' weights rose significantly during each subsequent year. Median weight gains were 0.9 kg (P less than 0.005) during the first year, 1.4 kg (P less than 0.005) during the second year, 0.9 kg (P less than 0.05) during the third year and 1.4 kg (P less than 0.05) during year 4. No such weight gain was recorded in a control group of 30 patients matched for age and duration of diabetes and treated by twice daily insulin injections. Multiple insulin injection regimens used over prolonged periods in a routine clinic setting do not alter metabolic control. However, continuing weight gain appears to occur despite similar daily insulin doses.


An immunopotentiator of beta-1,6;1,3 D-glucan prevents diabetes and insulitis in BB rats.

The preventive effect of an immunopotentiator, beta-1,6;1,3 D-glucan, on the development of diabetes and insulitis was studied in BB rats. The intravenous administration of 1 mg kg-1 week-1 of beta-1,6;1,3 D-glucan from the age of 4 weeks decreased the cumulative incidence of diabetes from 43.3% (13/30) to 6.7% (2/30) (P less than 0.005) and also the incidence of insulitis from 82.4% (14/17) to 26.3% (5/19) at the age of 20 weeks (P less than 0.002). Eight of nine rats were free from diabetes for 5 weeks after stopping beta-1,6;1,3 D-glucan at the age of 20 weeks. The total numbers of leukocytes in the peripheral blood and spleen of the rats were increased by beta-1,6;1,3 D-glucan treatment (P less than 0.05), whereas their T lymphocytes subsets were not changed. These data indicate that immunopotentiators could modulate the autoimmune mechanisms directed to pancreatic islets and inhibit the development of diabetes in BB rats.


Viscosity modulates blood glucose response to nutrient solutions in dogs.

The relationship between postprandial blood glucose levels and meal viscosity was studied by adding various combinations of hydroxypropylmethylcellulose to glucose solutions and administering them to female mongrel dogs. Glucose was administered as 5% or 20% solutions in water. Hydroxypropyl-methylcellulose was dissolved in the glucose solutions to yield low (5000 cP measured at 37 degrees C and 1 s-1), medium (15,000 cP) or high (30,000 cP) viscosities. High viscosity hydroxypropylmethylcellulose significantly reduced the maximum blood glucose concentration, Cmax, by 60% (5% glucose meal) and 40% (20% glucose meal) while reducing the area under the blood level vs. time curve (AUC0-3 h) by 40-50%. Medium viscosity hydroxypropylmethylcellulose reduced the Cmax at both glucose levels, but reduced the AUC only for the 5% glucose meal. Low viscosity HPMC lowered the Cmax only after the 5% glucose meal, and had no significant effect on the AUC at either glucose level. The average time to reach maximum concentration, Tmax, was prolonged two- to three-fold at all viscosity levels for the 5% glucose solutions, but was not affected when 20% glucose solutions were administered. It was concluded that hydroxypropylmethylcellulose can effectively retard the absorption of glucose from the gastrointestinal tract, and that the extent of this effect is related to the viscosity of the solution administered.


Short- and long-term gliclazide effects on pancreatic islet cell function and hepatic insulin extraction in non-insulin-dependent diabetes mellitus.

Nine non-obese males with non-insulin-dependent diabetes mellitus (NIDDM) were evaluated before and after 3 and 12 months (6 patients) treatment with the second generation hypoglycemic sulfonylurea: gliclazide. They underwent an oral glucose tolerance test, intravenous glucose and arginine tests measuring plasma insulin and C-peptide responses. Pre-hepatic insulin production and insulin delivery to peripheral tissues were calculated by deconvolution techniques and hepatic extraction of insulin estimated. An improvement was observed in the beta-cell function of the patients on gliclazide treatment: reduction of fasting plasma glucose associated with a progressive increase in C-peptide level but insulin levels decreased at 12 months, suggesting an increase in hepatic insulin extraction at this time. In the same way, while plasma glucose values after oral and i.v. glucose were greatly reduced at 3 and 12 months treatment, insulin did not change but C-peptide levels increased significantly at 12 month treatment. While the prehepatic insulin secretion rate increased progressively on gliclazide during all glucose challenges, the fractional hepatic insulin extraction fell after 3 and increased at 12 month treatment, with opposite changes in insulin delivered to peripheral tissues. Thus the insulinogenic effect of gliclazide could be masked during long-term administration by a concomitant effect of gliclazide which increases hepatic extraction of insulin. The maintenance of the responsiveness to the non-glucose secretagogue, arginine, as evaluated by the C-peptide levels, before and after correction of hyperglycemia, suggested improvement of beta-cell sensitivity to glucose after sulfonylurea treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


The association of waist-hip ratio and risk factors for development of IDDM complications in an IDDM adult population.

The role of waist-to-hip ratio (WHR) in the metabolic disturbance of IDDM has not been widely explored. Cross-sectional data from the Epidemiology of Diabetes Complications Study were used to examine the associations between WHR and risk factors for IDDM complications such as lipid or lipoprotein levels, blood pressure and fibrinogen. A total of 586 adults (greater than or equal to 18 years of age) were examined. WHR was calculated as the mean of duplicate waist circumference measurements made at mid-point between the iliac crest and the lower costal margin in mid-axillary line divided by the mean of duplicate maximum hip measures. WHR was positively correlated with total cholesterol, LDL-cholesterol, triglycerides, systolic and diastolic blood pressure and fibrinogen univariately for both sexes. WHR was negatively correlated with HDL-cholesterol. These correlations remained significant after adjustment for age among females and became less strong, although still significant, for males. The independent effects of WHR to these IDDM risk factors, assessed by multiple linear regression, indicated WHR was related to adverse lipid and lipoprotein levels, but not to fibrinogen or blood pressure. These findings underscore the importance of targeting intervention to IDDM individuals who have a high WHR to reduce known risk factors for IDDM complications especially those for cardiovascular disease, and is consistent with the hypothesis that insulin resistance may have a role to play in IDDM complications.


The response of glycated albumin to blood glucose change in the circulation in streptozotocin-diabetic rats--comparison of theoretical values with experimental data.

The contribution of the preceding blood glucose level to glycated protein was theoretically analyzed using a linear kinetic model and was compared with experiments using streptozotocin-diabetic rats. We assumed that the glycation process can be described by one irreversible step and that the fraction of glycated protein is small. A formula based on these two assumptions showed that the level of glycated protein was proportional to the weighted mean blood glucose concentration in the preceding period and that the weight function was determined by the metabolic characteristics of each protein. For assessing the usefulness of the present formula, the value calculated for the response of glycated albumin (GA) to acute blood glucose change in streptozotocin-diabetic rats was compared with the data obtained under three experimental conditions. The calculated responses of GA showed a little more retardation than the observed data, but showed enough agreement with them.


Teratogenic effects of tolbutamide on early-somite mouse embryos in vitro.

The present study investigated the teratogenicity of the oral hypoglycemic agent, tolbutamide, using an in vitro approach, and evaluated the role of its main metabolic effect, hypoglycemia. Teratogenesis was evaluated by culturing early-somite mouse embryos for 24 h in serum from rats treated with tolbutamide (79-117 micrograms/ml) or normal rat serum supplemented with tolbutamide (110-152 micrograms/ml). Tolbutamide-treated serum was then supplemented with glucose to control for potential effects of hypoglycemia. Mouse embryos demonstrated high malformation rates following exposure to serum from tolbutamide-treated rats (79%) or normal rat serum supplemented with tolbutamide (85%) compared with controls (4%), and defects included cardiac, ocular, neural tube, and somite abnormalities. Overall growth was reduced in treated embryos and yolk sacs, as determined by total protein contents. Embryonic growth and malformation rates were not improved by glucose supplementation of hypoglycemic tolbutamide-treated serum. Thus, tolbutamide produces malformation in mouse embryos in vitro at concentrations comparable to those in human serum, and the effects do not appear to be mediated by hypoglycemia. The potential risk of tolbutamide on the developing embryo must be considered in the therapy of pregnant diabetic patients.


The effects of superphysiologic hyperinsulinemia on glucose and lipid metabolism in glucose-tolerant offspring of patients with non-insulin-dependent diabetes mellitus (NIDDM).

First-degree relatives of patients with NIDDM manifest severe insulin resistance despite normal glucose tolerance test. To examine the mechanisms underlying the normal glucose tolerance, we evaluated the serum glucose/C-peptide/insulin dynamics and free fatty acid (FFA) as well as substrate oxidation rates and energy expenditure (EE) (indirect calorimetry) in nine young offspring of NIDDM patients (mean +/- SEM age 30 +/- 2.3 years, body mass index 24.2 +/- 1.2 kg/m2). Nine age-, sex- and weight-matched, normal subjects with no family history of diabetes served as the controls. Metabolic parameters were measured before, during and after a two-step glucose infusion (2 and 4 mg/kg.min) for 120 min. Mean basal serum glucose, insulin and C-peptide levels were similar in both groups. During 2 mg/kg.min glucose infusion, mean serum insulin and C-peptide rose to significantly (P less than 0.05-0.02) greater levels in the offspring vs. controls, while serum glucose levels were similar. With the 4 mg/kg.min glucose infusion, mean serum glucose, insulin and C-peptide levels were significantly (P less than 0.02-0.001) greater in the offspring at 100-120 min. Isotopically-derived (D[3-3H]glucose), basal hepatic glucose output (HGO) was not significantly different between the offspring vs. controls (1.86 +/- 0.30 vs. 1.78 +/- 0.06 mg/kg.min). During glucose infusion, basal HGO was partially suppressed by 66% at 60 min and by 100% at 120 min in the offspring. In contrast, HGO was completely (100%) suppressed at both times in the controls. Following cessation of glucose infusion, HGO rose to 1.64 +/- 0.12 mg/kg.min in the offspring and 1.46 +/- 0.05 mg/kg.min in the controls (P less than 0.05) between 200 and 240 min. These were 88% and 82% of the respective basal HGO values. At low glucose infusion (t = 0-60 min), the mean absolute, non-oxidative glucose disposal remained 1.5-fold greater in the offspring while at higher glucose infusion, nonoxidative glucose metabolism was not different in both groups. Throughout the study period, oxidative glucose disposal rate was not significantly different in both groups. The mean basal FFA was significantly greater in the offspring vs. controls (865 +/- 57 vs. 642 +/- 45 microEq/l). It was appropriately suppressed during glucose infusion to a similar nadir in both groups (395 +/- 24 vs. 375 +/- 33 microEq/l). The mean basal lipid oxidation was also significantly greater in the offspring than controls (1.06 +/- 0.05 vs. 0.75 +/- 0.04 mg/kg.min, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)


Antireticulin antibodies in sera of children with insulin-dependent diabetes mellitus.

Sera from 125 children (mean age 9.5 +/- 3.9; range 0.5-18 years) with newly diagnosed insulin-dependent diabetes mellitus were examined for the presence of antireticulin antibodies (ARA). Fifty-four of these children were followed up over a period of 150-400 days after the onset of the disease with respect to their serum ARA. The indirect immunofluorescence method on human and rat tissue was used to detect autoantibodies. In each serum, the level of islet cell antibodies (ICA) was determined. The prevalence of ARA in our diabetic children (16%) was significantly higher than in normal population (P less than 0.05). In sera of newly diagnosed ICA-negative children, ARA were more frequent than in ICA-positive patients (P less than 0.025). The difference in ARA prevalence was even higher when patients were divided into two groups one with less and one with more than 30 JDFu (P less than 0.005). On the contrary, sera sampled 150-400 days after the manifestation of IDDM revealed neither a positive nor a negative association between ICA and ARA. Thus, the negative association of ARA with ICA in the early stages of IDDM may suggest the role of an autoimmune response to reticulin in part of the IDDM patients, and gives further evidence to the heterogeneity of IDDM.


Comparative effects of captopril versus nifedipine on proteinuria and renal function of type 2 diabetic patients.

Our study compared the effects of an angiotensin-converting enzyme inhibitor (captopril) versus a calcium antagonist (nifedipine) on proteinuria and renal function in patients with diabetic nephropathy. A randomized follow-up study was designed. Type 2 diabetic patients, with established diabetic nephropathy (proteinuria greater than 0.5 g/24 h), were treated with nifedipine (10 patients, group A) or captopril (10 patients, group B) for 6 months. Arterial blood pressure, metabolic parameters, proteinuria and renal function were measured and compared. Mean percentage differences for glomerular filtration rate, renal plasma flow and filtration fraction between the two groups were calculated. No significant differences were observed in serum glucose, glycosylated hemoglobin (hemoglobin A1c), Na+, K+ or albumin in either group or between groups. Blood pressure decreased significantly with both treatments and mean blood pressure was significantly lower in group A compared with group B at 6 months (Mann-Whitney U-test, P = 0.03). Proteinuria was similar in both groups at randomization, but after 3 and 6 months of treatment significant reductions were observed only in the group treated with captopril (P less than 0.01). A significant decrease in filtration fraction was observed in group B with an increase in group A (Mann-Whitney U-test, P = 0.03). Multiple regression analysis identified the therapeutic agent administered as an independent variable for decrease in proteinuria. It is concluded that antihypertensive treatment with captopril, but not with nifedipine, reduced proteinuria in patients with diabetic nephropathy, although a better mean blood pressure was obtained with nifedipine.(ABSTRACT TRUNCATED AT 250 WORDS)


The value of glycosylated haemoglobin as a substitute for the oral glucose tolerance test in the detection of impaired glucose tolerance (IGT).

In a prospective study of South African Indian subjects with IGT, glycosylated hemoglobin [specifically HbA1 (HbA1(a+b+c)] and its relationship to the oral glucose tolerance test (OGTT) was studied in 128 study subjects who were classified IGT a year previously (Year 0 of study) and in 64 control subjects. At Year 1 of the study, the standard 75-g OGTT was performed on all subjects; study subjects were further divided into three groups based on World Health Organisation criteria [Normal (N), impaired glucose tolerance (IGT), diabetes mellitus (D)]. HbA1, a glycosylated hemoglobin (GHb), was measured by a cation-exchange microchromatographic method. Based on OGTT results, 47 of the 128 study subjects were classified IGT, 41 diabetes (newly-diagnosed diabetes) and 40 subjects had normal glucose tolerance. Mean GHb was significantly higher in the D group (7.61 +/- 1.76%) compared to the control group (6.99 +/- 1.22%) and the N group (6.9 +/- 1.12%), respectively (P less than 0.05); there was no significant difference between the IGT group (7.48 +/- 1.44%) and each of the other three groups. Compared to the OGTT, GHb was relatively insensitive in the diagnosis of IGT or diabetes mellitus: only 17% of the IGT group and 26.8% of the D group has elevated GHb values; the specificity of GHb as a measure of normal glucose tolerance was 85.9%. The majority of subjects, irrespective of the category of glucose tolerance, had GHb levels within the normal range and there was marked overlap between the four groups.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of insulin on serum amino-terminal propeptide of type III procollagen in non-insulin-dependent diabetes mellitus.

The effect of insulin on the serum levels of the amino-terminal propeptide of type III procollagen (PIIINP) was investigated in patients with non-insulin-dependent diabetes mellitus, whose disease was unsatisfactorily controlled by oral drugs. Before insulin therapy the PIIINP values of the patients (3.2 +/- 1.3 micrograms/l, n = 38) varied within the range of healthy subjects (3.1 +/- 0.6 micrograms/l, n = 50, NS). Insulin therapy (6-20 IU at bedtime plus the oral drugs) improved the glycemic control and increased the serum PIIINP during a 4 week (3.1 +/- 0.9 to 3.8 +/- 1.1 micrograms/l, P less than 0.01, n = 8) and an 8 week period (3.2 +/- 1.3 to 3.8 +/- 1.6 micrograms/l, P less than 0.001, n = 22). The values were still elevated after 6 months on insulin (3.5 +/- 1.5 to 4.0 +/- 1.7 micrograms/l, P less than 0.01, n = 12). Placebo-insulin did not alter the concentration of PIIINP (3.1 +/- 0.6 to 2.8 +/- 0.6 micrograms/l, NS, n = 8) whereas the glycemic control improved and body weight decreased. The PIIINP values correlated with fasting insulin before (r = 0.403, P less than 0.05, n = 30) and after the therapy (r = 0.452, P less than 0.001, n = 60). Insulin therapy, while correcting the hormone deficiency and restoring glucose and protein metabolism, seems to activate the synthesis of type III procollagen in patients with NIDDM. This may promote the atherosclerotic process.


Identification of early metabolic defects in diabetes-prone Australian aborigines.

The aim of the present study was to identify in young, diabetes-prone subjects the early abnormalities which may predispose to the development of type 2 diabetes. We studied 10 full-blood Australian Aborigines all of whom had a family history of diabetes and who were from an urbanised community with a high prevalence of this disorder. They were compared to 10 age- and body-mass-index-matched Caucasian controls with no family history of diabetes. Glucose kinetics were measured basally and following an oral glucose load. Fasting plasma glucose was equal in the two groups, but 2 h following the 75 g glucose load, the Aboriginal subjects had higher glycaemia than the controls (P less than 0.01). Insulinaemia was higher in the Aborigines both basally and following the glucose drink (P less than 0.05). Despite the hyperinsulinaemia, hepatic glucose production was higher in the Aboriginal subjects (P less than 0.01), while metabolic clearance rate was lower. It is concluded that in young Australian Aborigines with a strong family history of type 2 diabetes, both hepatic and peripheral insulin resistance are early abnormalities.


Prevalence of childhood diabetes in an urban population in south India.

The objective of the study was to estimate the prevalence of insulin-dependent diabetes in children less than or equal to 15 years in an urban area in south India, by a population study. Three zones from the northeastern part of the city demarcated by the Directorate of Census were chosen. Ascertainment of the cases from these zones was made (a) by collecting data from the major hospitals and diabetes clinics by personal visit; (b) by questionnaire sent to medical practitioners in the area; and (c) from the chemists and druggists who sell insulin. Recommendations of the Diabetes Epidemiology Research International Registry Group were used. Thirty children with insulin-dependent diabetes with age at diagnosis less than or equal to 15 years were identified. The prevalence was 0.26/1000. The peak age at diagnosis was 12 years. This first population-based study of prevalence of insulin-dependent diabetes in south India shows that insulin-dependent diabetes is not rare. It is higher than reported from many other Asian countries.


The influence of seaprose on erythromycin penetration into bronchial mucus in bronchopulmonary infections.

In bronchopulmonary infections antibiotics can be combined with other drugs, called mucoactive drugs, that act to reduce the abnormal viscoelasticity of the mucus enabling a deeper penetration of more antibiotic into the mucus. Seaprose is a protease that interacts with the polymeric fibrillar structure of the bronchial mucus to shorten the long chains of mucoproteins, DNA and other macromolecules, thus reducing the viscosity of the mucus. In order to assess whether the combination of seaprose (60 mg/8 h) plus erythromycin (500 mg/8 h) allows higher antibiotic levels in sputum than erythromycin (500 mg/8 h) plus placebo, the pharmacokinetic behaviour in sputum and in blood of these two treatments was investigated in a double-blind study in two groups of twenty patients each with bronchopulmonary infections. Serum and sputum levels were determined for each patient at the first and seventh day of the two drug regimens. Statistically significant differences for peak, AUC and MRT, were observed for erythromycin between the first and last dose in the group of patients treated with seaprose plus erythromycin; moreover significant differences for these parameters were observed between the two groups. These findings indicate the presence of a pharmacokinetic synergism between seaprose and erythromycin which allows erythromycin to penetrate bronchial secretion more easily and in higher amounts, performing a sterilizing action with therapeutic advantages.


Protective effect of levodropropizine against cough induced by inhalation of nebulized distilled water in patients with obstructive lung disease.

Levodropropizine is a recently developed, peripherally active antitussive agent which is widely used in clinical practice. In order to obtain further information on the spectrum of activity of this compound in experimental clinical models, a double-blind controlled study was carried out to evaluate the potential effect of the drug against cough and bronchoconstriction induced by inhalation of an ultrasonically nebulized solution of distilled water in patients with obstructive lung disease. Twenty patients were randomly divided into two groups, which received levodropropizine (60 mg t.i.d.) or placebo respectively for 7 consecutive days. Parameters evaluated at baseline and on the last day of treatment included (i) results of respiratory function tests (FEV1, IVC, FVC, TIFF, PEF, MEF75, MEF50, MEF25) performed before the stimulation test with nebulized water; (ii) total number of coughs during a 2-hour period after the stimulation test; (iii) bronchial responsiveness, quantified by calculating the volume of nebulized water required to induce a 20% reduction of FEV1 below the basal level. At pretreatment, the tussive response was very similar in the two groups. A significant decrease in number of coughs (from 34.4 +/- 8.4 at baseline to 15.6 +/- 4.9 post-treatment, p less than 0.01) was observed after administration of levodropropizine, whereas placebo treatment produced no significant effect (number of coughs: 29.6 +/- 4.9 at baseline vs 24.8 +/- 9.6 post-treatment, N.S.). Bronchial responsiveness decreased significantly (compared to baseline) in both treatment groups, without any significant difference between drug and placebo. Respiratory function tests were not significantly affected by either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of macrolides on ultrastructure of Staphylococcus aureus during postantibiotic phase.

The postantibiotic effects (PAEs) of macrolide antibiotics, such as midecamycin acetate (Miocamycin, MOM), erythromycin (EM), josamycin (JM) and clarithromycin (CAM), on Staphylococcus aureus and the ultrastructure of the pathogen during the postantibiotic phase were investigated. After exposure to 2 x MIC for 2 h, MOM showed the longest PAE of 3.9 h, while EM, JM and CAM showed PAE durations 1.2, 2.5 and 1.9 h, respectively. On examining the serum levels of these agents in man, the longest PAE of 2.4 h was induced by exposure to MOM. JM and CAM induced PAEs for durations of 1.4 and 1.3 h, but EM hardly induced the PAE. The ultrastructure was examined by transmission electron microscopy, and thick cell walls with an undulating outer layer and a multiple thick cross-section were observed for 4 h after exposure to 2 x MIC of MOM for 2 h. After exposure to 2 x MIC of EM, JM and CAM for 2 h, ultrastructural changes were observed for 1, 2 and 2 h, respectively. The size of these cells was about 1.5 to 2 times larger than the normal cells. Ultrastructural changes in S. aureus were observed during the PAE phase of each macrolide.


Efficacy of tosufloxacin in the treatment of experimentally induced intra-abdominal infections in rats.

A reproducible experimental model of intra-abdominal infections in rats has been devised in order to simulate intra-abdominal sepsis in patients. Preoperatively, the rats were fed with lean ground beef for two weeks in order to change the intestinal flora to one similar to that of humans. A 1-cm segment of ileum was isolated on its vascular pedicle. The intestine was then divided at each end of the segment and intestinal continuity was reestablished by an end-to-end anastomosis. The segment of ileum was then returned to the abdominal cavity. This experimental model was used to compare the efficacy of tosufloxacin alone and in combination with metronidazole, with the combination gentamicin and metronidazole in the treatment of intra-abdominal infections. Eighty per cent of the untreated animals died within three days. Within three days 20% of the animals receiving tosufloxacin died. Animals treated with tosufloxacin plus metronidazole or gentamicin plus metronidazole had a significantly decreased mortality and increased cure rates during the experimental period. Only 5% of these animals died. Thus the combination of tosufloxacin and metronidazole seems to be as successful as gentamicin plus metronidazole in the treatment of intra-abdominal infections.


Compared kinetics of 2-(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 016) and its active metabolite 2-(2,3-dihydro-5-hydroxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 005) in plasma and bronchial alveolar liquid in mice.

The concentration of 2-(2,3-dihydro-5-acetoxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 016) and its active metabolite 2-(2,3-dihydro-5-hydroxy-4,6,7-trimethylbenzofuranyl) acetic acid (IRFI 005) in bronchial alveolar liquid (BAL) and plasma of mice were studied. IRFI 016 and its active metabolite IRFI 005 are both present in BAL and plasma after oral administration of IRFI 016. In BAL no delay times were noted, in comparison with plasma, regarding Cmax time nor significant variation of t1/2 and the elimination constant (Kel). IRFI 016, orally administered, is very rapidly absorbed and, both in unaltered form and as its active metabolite, reaches the anatomic site where it carries out its principal pharmacological activity, according to the same kinetic course observed in plasma.


Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases.

Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e. type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients. The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels. In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


First effects of warning labels on alcoholic beverage containers.

Health warning labels are now required on alcoholic beverage containers in the United States. This study addresses who has seen these labels and respondents' reported changes in relevant knowledge, attitudes and behavior. Random samples of adults in the general population of the United States were interviewed by telephone 6 months prior to and 6 months after the enactment in November 1989 of the warning label law (N = 2006 and 2000, respectively). Six months after introduction of warning labels, over one fifth of the respondents reported having seen the labels. Greater proportions of key target groups, such as heavy drinkers and young men at risk for drunk driving, reported seeing the warnings. No statistically significant changes in knowledge of the health risks included on the labels were detected, but we found that knowledge levels for two non-included potential warnings had declined somewhat. After controlling for demographics and alcohol consumption, respondents who probably saw the warning labels were significantly more likely to report several behaviors indicative of heightened awareness of, and caution regarding, the hazard of drinking and driving and of drinking during pregnancy, hazards that are both included on the warning labels.


Alcohol consumption and rates of personal violence in Australia.

A time-series analysis of suicide and homicide rates in Australia from 1966 to 1985 revealed that suicide rates were lower and homicide rates higher in years when more alcohol was consumed per capita. The association of alcohol consumption with homicide was expected, but the association with suicide was opposite to that predicted.


Attitude towards alcohol, church attendance and denominational identity.

This paper describes the development of a 16-item Likert scale of attitude towards alcohol. Data derived from 315 individuals, concerned with various forms of youth work in England, demonstrate that both denominational affiliation and frequency of church attendance are significant determinants of attitudes towards alcohol. Membership of the Free Churches and frequent church attendance are associated with less liberal attitudes. These conclusions are discussed against the background of previous discrepant findings relating religiosity with alcohol use and abuse and contemporary sociological theories regarding the compartmentalisation of religious beliefs.


Unidimensionality of alcohol dependence syndrome?

To evaluate the coherence of Alcohol Dependence Syndrome (ADS), as per DSM-III-R criteria, 72 and 223 subjects with alcohol dependence disorder from Hospital and Community settings, respectively, were interviewed. Nine DSM-III-R criteria assessing the dependence syndrome were factor-analysed. A single factor model provides an adequate description of the interrelationship among the nine criteria and supports the coherence of the dependence syndrome for the hospital sample but not for the community. A two factor model, namely 'withdrawal' and 'social', fits the community data. When the criteria were combined into cumulative scales, they formed good approximations of unidimensional Guttman scales for both the hospital and community settings. For hospital data, preoccupation was the highly central criterion (lambda = 0.95) in defining the dependence syndrome while 'can't stop' (v = 0.11) measured the most severe level of dependence. In the community the 'socially dysfunctional use' identified as a separate secondary factor measured the most severe level of dependence.


Effects of ethanol and toluene on fixed-ratio performance in short sleep and long sleep mice.

This study examined the effects of ethanol (EtOH) and toluene on fixed-ratio (FR) responding in mice selectively bred for sensitivity to the effects of EtOH on sleep time. Although the more sensitive long sleep (LS) mice showed greater EtOH-induced impairment in a motor performance task than did the less sensitive short sleep (SS) mice, changes in FR performance in the two lines did not differ in response to EtOH, regardless of route (oral or intraperitoneal) or time (40 vs. 60 min pre-session) of administration. These results emphasize the importance of considering task variables in determination of the behavior of different genotypes. In contrast to results with EtOH, the volatile inhalant toluene produced different effects on FR responding in the selected lines, with SS mice being more sensitive than LS mice.


Psychiatric symptoms in drug abusing adolescents.

Psychiatric symptoms and psychosocial variables were investigated in 46 adolescent drug abusers referred to a psychiatric clinic. There were high rates of behavioural symptoms (mostly oppositional and delinquent), emotional symptoms (mostly depressive) and an abundance of adverse life events and family dynamics. When compared to a control group of non-abusing adolescents, drug users were only more behaviourally disturbed. Cluster analysis of the drug abusing adolescents showed that they fell into three distinct groups of (1) behavioural dysfunction (76%); (2) family dysfunction (16%); and (3) emotional dysfunction (8). The clinical implications of these findings are discussed.


Adolescent drug use, health and personality.

Four factors have confounded the association between drug use and morbidity: (a) known drug users may be less healthy than unknown drug users; (b) drug users are rarely compared to control subjects; (c) the socio-economic status of drug users predisposes them to ill-health; (d) the personality of drug users predisposes them to ill-health. Here, controlling for these confounds, in a study of 210 adolescent drug users it was found that subjective ill-health was more strongly related to drug use than was objective ill-health. Drug use was related to neuroticism and psychopathic deviance. Controlling for personality, drug use accounted for little additional variance in health. It is concluded that drug use and health are not strongly related amongst adolescent drug users, although, because of their personalities, drug users tend not to feel well. Implications are discussed for the self-treatment explanation of drug use and for the design of preventative programmes.


[Physical exercise tolerance in chronic obstructive emphysematous bronchitis and coronary heart disease under antiobstructive therapy].

19 consecutive patients (18 men, one woman, mean age 61.4 [49-73]years) with chronic obstructive airways disease (bronchitis and emphysema) together with angiographically confirmed coronary heart disease were studied to investigate their cardiopulmonary exercise tolerance and the effects of bronchodilators on their myocardial ischaemia. Because they were receiving drug therapy for angina or because they had previously undergone aortocoronary bypass operation or balloon dilatation, the patients were symptom-free. In three cases slight ischaemia was demonstrable during maximal exertion. Aerobic and anaerobic exercise capacity was determined by spiroergometry after inhalation of salbutamol (S, 0.2 mg) alone or in combination with oxitropium bromide (O, 0.2 mg). The supplementary effect of oral theophylline (T, 15 mg/kg.day) was studied in 13 patients. In terms of maximal aerobic exercise tolerance the following improvements were noted: energy output (watts): S: + 6.3%; S and O: + 12.3% (P < 0.05); S, O and T: + 14.0% (P < 0.01). Oxygen uptake (ml/min): S: + 8.2% (P < 0.05); S and O: + 18.2% (P < 0.01); S, O and T: + 35.4% (P < 0.01). Maximum exercise capacity was not significantly improved, although maximum oxygen uptake was significantly increased by the two-drug combination by 16.9% (P < 0.05) and by the three-drug combination by 19.2% (P < 0.05). Maximum minute volume and tidal volume rose significantly, though respiratory rate was unchanged. Heart rate and blood pressure remained practically unaffected by the treatment, both at rest and during exertion. There was no evidence of significant aggravation of ventricular arrhythmias or of ischaemia during ergometric testing.


[Regional hyperthermic fibrinolytic perfusion in postoperative deep venous thrombosis of the leg].

Four days after an operation for fusion of lumbar and sacral vertebrae a 30-year-old man developed bilateral deep-vein thrombosis in the legs, extending on the left from the fibular group of veins to the popliteal vein. On the right all deep veins of the lower leg were occluded, including the confluence of the popliteal vein. As systemic fibrinolysis was contraindicated, surgical thrombectomy was undertaken. After incomplete removal of the thrombi, regional hyperthermic perfusion with streptokinase was performed using a heart-lung machine. After a compression bandage had been applied to the right leg above the veins the leg was perfused via the common femoral vein at 40 degrees C from the heart-lung machine, at a flow rate of 600-800 ml/min, for 60 min with a solution containing 1 million IU streptokinase. Measurement of various components in the perfusate indicated marked fibrinolysis (fibrinogen: not measurable; fibrinogen breakdown products: > 80 micrograms; streptokinase: 100 FU/ml after 30 min, 62 FU/ml after 60 min). At the same time there was no demonstrable fibrinolytic activity in the systemic circulation. Fibrinogen concentration fell from 340 mg/dl 30 min before the onset of perfusion to 245 mg/dl 90 min after it. After 60 min of perfusion the blood from the right leg was discarded and the leg flushed through with 1.5 l of an electrolyte solution and then filled up with previously obtained and stored patient's own blood concentrate. Subsequent phlebography and venous occlusion plethysmography demonstrated complete recanalization of the deep-vein system with normal venous valve function.


[Carbohydrate and lipid metabolism following heart bypass operations. The effect of the intravenous hypocaloric administration of glucose versus glucose xylitol (1:1)].

The effect of glucose-xylitol infusion on carbohydrate and lipid metabolism was investigated in 18 metabolically normal men (mean age 56.1 [35-65] years) with coronary heart disease after they had undergone a coronary artery bypass operation. During the first postoperative hours, group I (n = 6) received glucose only (2 mg/kg.min), group II (n = 6) glucose+xylitol (1 mg/kg.min each), and group II a glucose-containing electrolyte solution (0.83 mg/kg.min glucose). Blood glucose and insulin concentrations during the infusion period were significantly (P < 0.05) lower in groups II and III than I (glucose after 6 h: group I 21.5 [15.3-26.8] mmol/l; group II 14.2 [11.2-18.1] mmol/l; group III 12.6 [6.8-16.0] mmol/l). The highest lactate concentrations were reached in group I, 6 hours after the operation. Palmitine and stearine, as well as oleic and linoleic acid concentrations were significantly lower 12 hours postoperatively in group I than groups II and III (P < 0.05). These data indicate that energy-ineffective high glucose concentrations were avoided and endogenous lactate production reduced by the postoperative infusion of glucose+xylitol. In addition, it achieved a higher supply of free fatty acids as energy source to the myocardium without reaching toxic concentrations in the postischaemic myocardium.


[The color Doppler-guided compression therapy of a large false aneurysm of the femoral artery following left heart catheterization].

A ventrally located false aneurysm (7 x 5.2 x 3.4 cm) of the right common femoral artery occurred, after left-heart catheterization by the Judkins technique via this artery, in an 83-year-old woman with aortic valve stenosis. Colour Doppler sonography demonstrated a puncture canal (neck of the aneurysm) filling in both systole and diastole, as well as turbulent flow within the aneurysm. Flow into the aneurysm was considerably reduced when the transducer head compressed the aneurysm, while flow continued in the femoral artery and vein. This compression, maintained for 25 min, completely thrombosed the puncture canal and aneurysm so that no vascular surgery was required.


[Morbidity and mortality in type 1 and type 2 diabetes mellitus after the diagnosis of diabetic retinopathy].

One to ten years after laser coagulation for diabetic retinopathy, 229 type I diabetics (mean age 44.3 years) and 157 type II diabetics (mean age 65 years) were re-studied for morbidity and mortality (progression of late damage, duration of survival, cause of death). The duration of diabetes at the first laser coagulation averaged 23.1 years for type I diabetics (15.9 years for type II). Average period from the first laser coagulation to the re-examination was 6.5 years for type I, 5.1 for type II diabetics. Of those patients still alive 6.7% had gone blind (type II: 7.3%). 2.1% and 4.6%, respectively, were receiving dialysis treatment, while renal transplantation had been performed in 3.1 and 1.8%, respectively. Stroke was the most frequent macrovascular complications (8.4 and 16.5%), followed by leg amputation (3.6 and 14.7%) and myocardial infarction (3.7 and 18.3%). 83 patients had died: 35 (15.3%) type I and 48 (30.6%) type II diabetics. Causes of death were septicaemia 14.3% (0%), uraemia 11.4% (8.3%), myocardial infarction 14.3% (33.3%), heart failure 8.6% (29.2%) and stroke 5.7% (6.3%). 10.7% (24.2%) had died within the first 5 years after laser coagulation. Despite a lower incidence of blindness in patients with diabetic retinopathy, the vascular disease progresses in other vascular regions so that a large proportion of diabetics will develop renal failure or die early from macrovascular complications.