Exploratory Multisite MR Spectroscopic Imaging Shows White Matter Neuroaxonal Loss Associated with Complications of Type 1 Diabetes in Children.

BACKGROUND AND PURPOSE: Type 1 diabetes affects over 200,000 children in the United States and is associated with an increased risk of cognitive dysfunction. Prior single-site, single-voxel MRS case reports and studies have identified associations between reduced NAA/Cr, a marker of neuroaxonal loss, and type 1 diabetes. However, NAA/Cr differences among children with various disease complications or across different brain tissues remain unclear. To better understand this phenomenon and the role of MRS in characterizing it, we conducted a multisite pilot study. MATERIALS AND METHODS: In 25 children, 6-14 years of age, with type 1 diabetes across 3 sites, we acquired T1WI and axial 2D MRSI along with phantom studies to calibrate scanner effects. We quantified tissue-weighted NAA/Cr in WM and deep GM and modeled them against study covariates. RESULTS: We found that MRSI differentiated WM and deep GM by NAA/Cr on the individual level. On the population level, we found significant negative associations of WM NAA/Cr with chronic hyperglycemia quantified by hemoglobin A1c (P < .005) and a history of diabetic ketoacidosis at disease onset (P < .05). We found a statistical interaction (P < .05) between A1c and ketoacidosis, suggesting that neuroaxonal loss from ketoacidosis may outweigh that from poor glucose control. These associations were not present in deep GM. CONCLUSIONS: Our pilot study suggests that MRSI differentiates GM and WM by NAA/Cr in this population, disease complications may lead to neuroaxonal loss in WM in children, and deeper investigation is warranted to further untangle how diabetic ketoacidosis and chronic hyperglycemia affect brain health and cognition in type 1 diabetes.

["Do-not-rescuscitate"--Results of introducing a standardized order sheet on documentation quality]. / "Do not rescuscitate"--Auswirkungen der Einführung eines standardisierten Formulars auf Therapiebegrenzungen in der klinischen Praxis.

INTRODUCTION: DNR orders have been used internationally since the 1970 s. Despite the growing importance of patient preference in German law, there is little data on DNR orders in Germany Methods: The prevalence of DNR orders was assessed on the hospital wards. Healthcare were asked about their experiences and opinions in two polls. The charts of all deceased patients were reviewed for DNR notes for 9 month before and after introduction of the new DNR order sheets. RESULTS: The prevalence of DNR orders remained constant at 8% of patients. In 12,4% of these DNR status was not known by the nursing staff. After introduction of the order sheet, the percentage of orders with comprehensive documentation increased from 5.9 to 65.4% of orders (p < 0.001). In the polls the healthcare workers saw a significant improvement in information content of DNR orders after introduction of the new order sheets. The chart review documented an improved documentation of DNR status going up from 28.8 to 40.8% of deceased patients (p < 0.001). The fraction of comprehensive orders increased from 32% to 84.6% (p < 0.001). CONCLUSION: INTRODUCTION of DNR order sheets in a German hospital lead to objective improvements in the quality of end-of life care documentation while the prevalence of DNR orders remained unchanged.

Progressive decrease in N-acetylaspartate/Creatine ratio in a teenager with type 1 diabetes and repeated episodes of ketoacidosis without clinically apparent cerebral edema: Evidence for permanent brain injury.

Recent data suggest that DKA may contribute to cognitive impairment in children with type 1 DM. We measured the NAA/Cr ratio in a teenager during and following 2 separate episodes of DKA without clinically apparent cerebral edema. The NAA/Cr ratio decreased during DKA and improved following recovery. However, the NAA/Cr value was lower after the second episode of DKA (1.76) than after the first (1.97). These findings provide support for the hypothesis that neuronal injury may result from DKA.

Cerebral proton magnetic resonance spectroscopy in children with diabetic ketoacidosis.

BACKGROUND AND PURPOSE: Subclinical cerebral edema occurs in many, if not most, children with diabetic ketoacidosis (DKA) and may be an indicator of subtle brain injury. Brain ratios of N-acetylaspartate (NAA) to creatine (Cr), measured by proton MR spectroscopy, decrease with neuronal injury or dysfunction. We hypothesized that brain NAA/Cr ratios may be decreased in children in DKA, indicating subtle neuronal injury. MATERIALS AND METHODS: Twenty-nine children with DKA underwent cerebral proton MR spectroscopy during DKA treatment (2-12 hours after initiating therapy) and after recovery from the episode (72 hours or more after the initiation of therapy). We measured peak heights of NAA, Cr, and choline (Cho) in 3 locations within the brain: the occipital gray matter, the basal ganglia, and periaqueductal gray matter. These regions were identified in previous studies as areas at greater risk for neurologic injury in DKA-related cerebral edema. We calculated the ratios of NAA/Cr and Cho/Cr and compared these ratios during the acute illness and recovery periods. RESULTS: In the basal ganglia, the ratio of NAA/Cr was significantly lower during DKA treatment compared with that after recovery (1.68 +/- 0.24 versus 1.86 +/- 0.28, P<.005). There was a trend toward lower NAA/Cr ratios during DKA treatment in the periaqueductal gray matter (1.66 +/- 0.38 versus 1.91 +/- 0.50, P=.06) and the occipital gray matter (1.97 +/- 0.28 versus 2.13 +/- 0.18, P=.08). In contrast, there were no significant changes in Cho/Cr ratios in any region. CONCLUSIONS: NAA/Cr ratios are decreased in children during DKA and improve after recovery. This finding suggests that during DKA neuronal function or viability or both are compromised and improve after treatment and recovery.

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes.

Risk factors for cerebral edema in children with diabetic ketoacidosis. The Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics.

BACKGROUND: Cerebral edema is an uncommon but devastating complication of diabetic ketoacidosis in children. Risk factors for this complication have not been clearly defined. METHODS: In this multicenter study, we identified 61 children who had been hospitalized for diabetic ketoacidosis within a 15-year period and in whom cerebral edema had developed. Two additional groups of children with diabetic ketoacidosis but without cerebral edema were also identified: 181 randomly selected children and 174 children matched to those in the cerebral-edema group with respect to age at presentation, onset of diabetes (established vs. newly diagnosed disease), initial serum glucose concentration, and initial venous pH. Using logistic regression we compared the three groups with respect to demographic characteristics and biochemical variables at presentation and compared the matched groups with respect to therapeutic interventions and changes in biochemical values during treatment. RESULTS: A comparison of the children in the cerebral-edema group with those in the random control group showed that cerebral edema was significantly associated with lower initial partial pressures of arterial carbon dioxide (relative risk of cerebral edema for each decrease of 7.8 mm Hg [representing 1 SD], 3.4; 95 percent confidence interval, 1.9 to 6.3; P<0.001) and higher initial serum urea nitrogen concentrations (relative risk of cerebral edema for each increase of 9 mg per deciliter [3.2 mmol per liter] [representing 1 SD], 1.7; 95 percent confidence interval, 1.2 to 2.5; P=0.003). A comparison of the children with cerebral edema with those in the matched control group also showed that cerebral edema was associated with lower partial pressures of arterial carbon dioxide and higher serum urea nitrogen concentrations. Of the therapeutic variables, only treatment with bicarbonate was associated with cerebral edema, after adjustment for other covariates (relative risk, 4.2; 95 percent confidence interval, 1.5 to 12.1; P=0.008). CONCLUSIONS: Children with diabetic ketoacidosis who have low partial pressures of arterial carbon dioxide and high serum urea nitrogen concentrations at presentation and who are treated with bicarbonate are at increased risk for cerebral edema.

Cerebral edema in children with diabetic ketoacidosis.

Cerebral edema is the most frequent serious complication of diabetic ketoacidosis (DKA) in children, occurring in 1% to 5% of DKA episodes. The rates of mortality and permanent neurologic morbidity from this complication are high. The pathophysiologic mechanisms underlying DKA-related cerebral edema are unclear. A number of past and more recent studies have investigated biochemical and therapeutic risk factors for the development of cerebral edema. Recent studies have shown that a higher initial serum urea nitrogen concentration and lower initial partial pressure of carbon dioxide are associated with the development of cerebral edema. This and other information suggests that the pathophysiology of DKA-related cerebral edema may involve cerebral ischemia.

Acid-base homeostasis in children with growth hormone deficiency.

BACKGROUND: Although the primary use of growth hormone (GH) is to promote linear growth, it is also known to affect many metabolic processes and to influence renal function. In laboratory animals, growth hormone deficiency (GHD) causes a mild metabolic acidosis that is corrected by GH treatment. We observed a patient with GHD who initially presented with acidosis of unclear etiology and corrected the acidosis with GH treatment. OBJECTIVES: To determine: 1) whether children with GHD have lower mean serum bicarbonate concentrations than do children with short stature because of other causes; and 2) whether the presence of a low serum bicarbonate concentration increases the probability of GHD among children with short stature. METHODS: We collected data from the medical records of 143 children with short stature who had serum electrolyte concentrations measured as part of their initial evaluations, 66 with GHD and 77 with short stature as a result of other causes. We compared mean serum bicarbonate concentrations and bicarbonate standard deviation scores (SDS) between these two groups and determined the probability of GHD for patients according to bicarbonate SDS. RESULTS: The mean serum bicarbonate concentration was significantly lower in patients with GHD (mean standard deviation [SD]; 23.9 [0.4] mEq/L vs 25.2 [0.3] mEq/L) as was the bicarbonate SDS (-0.12 [0.14] SD vs 0.38 [0.10] SD). Twelve (75%) of 16 patients with bicarbonate SDS 1 SD. Patients with bicarbonate SDS between -1 SD and 1 SD had an intermediate probability of GHD, 46/102 (45%), similar to the overall prevalence of GHD in the study population (46%). Mean bicarbonate concentrations and bicarbonate SDS increased significantly in 9 patients who had repeat electrolyte measurements during treatment with GH (mean bicarbonate; 21.7 [1.1] mEq/L vs 26.9 [0.59] mEq/L, mean bicarbonate SDS; -1.24 [0.43] SD vs 0.55 [0.27] SD). CONCLUSIONS: Serum bicarbonate concentrations are lower in patients with GHD than in patients with short stature as a result of other causes. In addition, serum bicarbonate concentrations rise with GH treatment in patients with GHD. The probability of GHD is increased for patients with bicarbonate SDS 1 SD. These findings indicate a role for GH in maintaining normal acid-base homeostasis and suggest that GHD should be considered in children whose growth failure is attributed to other causes of acidosis.

Immunosuppressant neurotoxicity in liver transplant recipients. Clinical challenges for the consultation-liaison psychiatrist.

Neuropsychiatric problems are common among liver transplant recipients, and immunosuppressant neurotoxicity is an important etiologic factor in the posttransplant period. Four typical cases of immunosuppressant neurotoxicity are presented from the clinical experience of the University of California, Los Angeles-Dumont Liver Transplant program. All patients presented with acute behavioral symptoms and received urgent psychiatric consultation; each proved to be suffering from a variant of immunosuppressive-related neurotoxicity. Correlative neuroimaging studies and descriptions of clinical course are included. Psychiatrists are urged to become familiar with the signs, symptoms, differential diagnosis, neuroimaging findings, and management of immunosuppressive neurotoxicity and secondary psychiatric disorders in solid organ recipients.

Non-insulin dependent diabetes mellitus in Mexican-American children.

To define the clinical and metabolic characteristics of children with non-insulin-dependent diabetes mellitus (NIDDM), we reviewed the medical records of 18 children and adolescents who met either or both of the following criteria for the diagnosis of the disease: evidence of continued endogenous secretion of insulin beyond that expected in insulin-dependent diabetes mellitus and satisfactory glycemic control with diet alone or in combination with an oral hypoglycemic agent more than 2 years from the time of diagnosis. Patients who met these criteria but had islet cell antibodies or insulin autoantibodies were eliminated from the study group. Patients with NIDDM constituted 8% of all patients with diabetes seen in our pediatric clinics and 19% of diabetic patients of Central or South American ancestry. Of the 18 patients, 12 (67%) were Mexican American. The mean age of onset was 12.8 years (range, 5 to 17). Obesity (n = 9) and acanthosis nigricans (n = 12) were common findings. Ketonuria was present at diagnosis in 5 (33%) of 15 patients and acidosis in 2 of 14 (14%). Challenge with a nutritional supplement (Sustacal, Mead Johnson Nutritionals) (n = 10) showed a mean fasting serum C-peptide concentration of 1.19 nmol per liter (3.6 ng per ml). A family history of NIDDM was present in 13 (87%) of 15 patients, with 7 (47%) having 3 or more generations affected. Children with NIDDM are an important subset of those with diabetes, and this disease should be suspected in diabetic children presenting without ketoacidosis and with acanthosis nigricans, obesity, and a strong family history, particularly among those of Mexican-American ethnicity. Children with these characteristics should undergo testing of endogenous insulin secretion for appropriate therapeutic intervention.

Variation in the management of pediatric diabetic ketoacidosis by specialty training.

OBJECTIVE: To compare management strategies for pediatric diabetic ketoacidosis (DKA) among physicians with different specialty training. METHODS: We conducted a mail survey of 1000 randomly selected physicians, including 200 pediatric endocrinologists, 200 general emergency physicians, 200 pediatric emergency physicians, 200 pediatric intensivists, and 200 pediatric chief residents. We posed questions regarding a hypothetical 10-year-old patient with new onset of diabetes mellitus who is approximately 10% dehydrated but alert, with venous pH of 7.1 and serum glucose concentration of 34.7 mmol/L (625 mg/dL). Questions involved the rate of rehydration, content of intravenous fluids, insulin therapy, potassium replacement, use of sodium bicarbonate, and adjustments in therapy for decreasing serum glucose concentration. We compared responses of physicians in each specialty and used multiple regression analysis to adjust for potential confounding variables, including number of years in practice, number of children with DKA seen per month, and practice setting. RESULTS: Five hundred eighty-one physicians (58.1%) completed the survey, with responses demonstrating significant, consistent differences between specialties. Extremes of responses included the following: (1) 59% of endocrinologists vs 11% of general emergency physicians would give an initial fluid bolus of less than 20 mL/kg (odds ratio [OR], 11.7; 95% confidence interval [CI], 5.0-27.7) (P < .001); (2) 83.5% of general emergency physicians vs 42.5% of pediatric intensivists would administer an initial insulin bolus (OR, 4.1; 95% CI, 2.0-8.7) (P < .001); (3) 58.2% of pediatric intensivists vs 9% of general emergency physicians would replace fluids over a period of greater than 24 hours (OR, 14.1; 95% CI, 5.5-37.5) (P < .001); and (4) 54.3% of general emergency physicians vs 7.3% of pediatric intensivists would use potassium chloride alone for potassium replacement (OR, 10.8; 95% CI, 5.0-23.8) (P < .001). All of these differences persisted after adjusting for the potential confounding variables. CONCLUSIONS: Substantial differences exist in the management of pediatric DKA among physicians of different specialties, presumably due to differences in specialty training. These differences obscure our ability to evaluate the treatment of DKA and highlight the necessity for further studies comparing the outcomes of different treatment strategies.

Predictors of early remission of hyperthyroidism in children.

Children with hyperthyroidism often require prolonged courses of antithyroid medication to achieve remission, and long-term compliance is problematic. To determine which clinical and laboratory features predict early remission, we reviewed the records of 191 patients less than 19 yr old with Graves' disease. We compared patients achieving remission within 2 yr (group 1, n = 27) with those who completed more than 2 yr of medical therapy but did not achieve a remission (group 2, n = 79). Patients who were in neither of the above categories (n = 85) were excluded from the statistical analysis. Variables that were measurable at the time of diagnosis, recorded in more than 50% of the study population and associated with early remission in the univariate analysis (P < or = 0.05), were entered into a stepwise multiple logistic regression analysis. Variables retaining a significant association with early remission (P < 0.05) were considered independent predictors of early remission. Patients achieving early remission were older (mean, 12.5 vs. 10.9 yr, P = 0.039) and had higher body mass indexes (BMI, 19.0 vs. 16.6, P = 0.002), higher BMI SD scores (-0.03 vs. -0.60, P = 0.004), lower heart rates (110 vs. 121, P = 0.023), smaller goiters (group 1: 60% with moderate/large goiter; group 2: 83%, P = 0.050), lower platelet counts (272 vs. 339 K/microL, P = 0.006), lower serum T4 and T3 concentrations at presentation (T4: 18.3 vs. 22.5 microg/dL, P = 0.015; T3: 439 vs. 613 ng/dL, P = 0.008), and were less likely to have a positive test for thyroid stimulating Igs (group 1: 50% vs. group 2: 93%, P = 0.008). Regression analysis identified BMI SD score and goiter size as independent predictors of early remission (P < 0.05). Eighty-six percent of patients with BMI SD score above -0.5 SD and minimal/small goiters achieved early remission, compared with 13% of those with BMI SD score below -0.5 SD and moderate/large goiters. We conclude that, of multiple clinical and laboratory variables associated with early remission, BMI SD score and goiter size are independent predictors. Algorithms employing these two variables can be used to facilitate counseling of patients and expedite therapeutic decisions.

Non-insulin-dependent diabetes mellitus in childhood and adolescence.

NIDDM in children and adolescents represents a heterogeneous group of disorders with different underlying pathophysiologic mechanisms. Most subtypes of NIDDM that occur in childhood are uncommon, but some, such as early onset of "classic" NIDDM, seem to be increasing in prevalence. This observed increase is thought to be caused by societal factors that lead to sedentary lifestyles and an increased prevalence of obesity. In adults, hyperglycemia frequently exists for years before a diagnosis of NIDDM is made and treatment is begun. Microvascular complications, such as retinopathy, are often already present at the time of diagnosis. Children are frequently asymptomatic at the time of diagnosis, so screening for this disorder in high-risk populations is important. Screening should be considered for children of high-risk ethnic populations with a strong family history of NIDDM with obesity or signs of hyperinsulinism, such as acanthosis nigricans. Even for children in these high-risk groups who do not yet manifest hyperglycemia, primary care providers can have an important role in encouraging lifestyle modifications that might delay or prevent onset of NIDDM.

Home monitoring for infants at high risk for the sudden infant death syndrome.

The rate of sudden infant death syndrome (SIDS) In Israel is relatively low (0.5-0.9:1,000). Home cardiorespiratory monitoring (HM) is an accepted practice in infants at high risk for SIDS. We report our experience with 261 infants who were referred to our SIDS prevention program. They included: 52 preterm infants with apneas and bradycardias, 83 SIDS siblings (3 twins), 22 infants of drug-addicted mothers, and 104 infants after an idiopathic apparent life-threatening event (ALTE). HM was performed in 40 of 52 preterms, 38 of 83 SIDS siblings, all 22 infants of addicted mothers and 67 of 104 post-ALTE. All received 24 h/day medical and technical backup as well as emotional support, and were closely followed until 15 months of age. None of the 261 infants died. Five infants experienced six ALTEs that required resuscitative measures; another 28 infants had monitor alarms judged as real by the caregivers. The average duration of HM was 3.2 months (range 1-7). In 8 of 167 cases the parents stopped HM earlier than recommended, and in 34 of 167 cases (20%), parents continued HM beyond the time when discontinuation was recommended by the medical personnel. Among the caregivers, 85% found HM to be reassuring and stated that it helped them to conduct a normal life. We suggest that in our population, HM may have a favorable effect on family life. With close backup and support, most families will benefit from HM and will gain reassurance that will enable them to conduct normal life.

Obsessive compulsive disorder in a woman with left basal ganglia infarct: A case report.

This report presents a syndrome resembling obsessive convulsive disorder (OCD) secondary to a stroke in the left basal ganglia. The patient's syndrome is virtually identical to those that have been described in bilateral damage of the basal ganglia. However, the stroke described in this case report is located unilaterally in the left basal ganglia. In addition, experience in treating a patient with OCD induced by structural damage of basal ganglia is presented.

Founders hold the future of integrated provider organizations.

Success of an integrated delivery system will be based on a common understanding of the new business of integrated care delivery and the creation of a stable and organized provider structure. Physicians' income will be based on the efficiency and success of integrated provider organizations--how well they manage patients and how well providers work with their peers to promote high-quality care while managing the cost of care and its utilization.

Hermansky-Pudlak syndrome: case report and clinicopathologic review.

The Hermansky-Pudlak syndrome is an autosomal recessive disorder consisting of the triad of albinism, a bleeding diathesis, and ceroid deposition within the reticuloendothelial system. In this study of a patient with Hermansky-Pudlak syndrome, we demonstrate the presence of ceroid within dermal macrophages. Electron microscopic studies suggest that melanosomes may be a substrate for the formation of ceroid in the skin. A review of the clinical and pathophysiologic features of this disorder is presented.

AIDS-related angiomatosis.

We report multifocal cutaneous and mucosal vascular proliferations with the clinical and histological features of lobular capillary hemangioma and histiocytoid hemangioma in a 32-year-old acquired immunodeficiency syndrome patient. The lesions resolved subsequent to erythromycin therapy.