Body conformation in Great Danes with and without clinical signs of cervical spondylomyelopathy.

It has been suggested that a combination of large head and long neck cause abnormal forces on the cervical vertebral column and are involved in the pathogenesis of cervical spondylomyelopathy (CSM) in Great Danes. The aim of this study was to compare the body conformation of 15 clinically normal and 15 CSM-affected Great Danes. There were no statistically significant differences between clinically normal and CSM-affected Great Danes in any body measurements. There were no significant associations between body conformation and the severity of neurological signs or cervical vertebral body dimensions determined by magnetic resonance imaging in CSM-affected Great Danes. The results of this study do not support the hypothesis that differences in body conformation related to head size, neck length, and body height and length, play a role in the pathogenesis of CSM in Great Danes.

Cervical vertebral trabecular bone mineral density in Great Danes with and without osseous-associated cervical spondylomyelopathy.

BACKGROUND: Great Danes (GDs) with osseous-associated cervical spondylomyelopathy (CSM) have osteoarthritis (OA) of the cervical vertebrae. OA is often associated with increases in bone mineral density (BMD) in people and dogs. HYPOTHESIS/OBJECTIVES: To compare the trabecular BMD of the cervical vertebrae between clinically normal (control) GDs and GDs with osseous-associated CSM by using computed tomography (CT). We hypothesized that the vertebral trabecular BMD of CSM-affected GDs would be higher than that of control GDs. ANIMALS: Client-owned GDs: 12 controls, 10 CSM affected. METHODS: Prospective study. CT of the cervical vertebral column was obtained alongside a calibration phantom. By placing a circular region of interest at the articular process joints, vertebral body, pedicles, and within each rod of the calibration phantom, trabecular BMD was measured in Hounsfield units, which were converted to diphosphate equivalent densities. Trabecular BMD measurements were compared between CSM-affected and control dogs, and between males and females within the control group. RESULTS: Differences between CSM-affected and control dogs were not significant for the articular processes (mean = -39; P = .37; 95% CI: -102 to 24), vertebral bodies (mean = -62; P = .08; 95% CI: -129 to 6), or pedicles (mean = -36; P = .51; 95% CI: -105 to 33). Differences between female and male were not significant. CONCLUSIONS AND CLINICAL IMPORTANCE: This study revealed no difference in BMD between control and CSM-affected GDs. Based on our findings no association was detected between cervical OA and BMD in GDs with CSM.

Cervical spondylomyelopathy in Great Danes: a magnetic resonance imaging morphometric study.

Morphometric investigations comparing normal and affected animals increase our understanding of spinal diseases in dogs. The aim of this study was to generate morphometric data for osseous-associated cervical spondylomyelopathy (CSM) in Great Danes (GDs). Magnetic resonance imaging (MRI) morphometric features of the cervical vertebral column of GDs with and without clinical signs of CSM were characterized and compared. Thirty client-owned GDs were prospectively enrolled, including 15 clinically normal and 15 CSM-affected GDs. All dogs underwent MRI of the cervical to thoracic vertebral column (C2-C3 through T1-T2). Areas of the cranial and caudal articular processes, and the height, width and areas of the vertebral canal and spinal cord were determined. Middle foraminal heights were measured. Intervertebral disc width was measured before and after traction. Intraobserver and interobserver agreement were calculated. CSM-affected GDs had larger areas of the caudal articular processes from C2-C3 through T1-T2. In CSM-affected GDs, the vertebral canal and spinal cord areas were significantly smaller at C5-C6 and C6-C7, the vertebral canal width was significantly narrower at C6-C7 and C7-T1, and the spinal cord width was significantly narrower at C5-C6 and C6-C7. Middle foraminal height was smaller in CSM-affected GDs from C3-C4 through C7-T1. Neutral intervertebral disc widths were smaller in CSM-affected GDs. It was concluded that the cervical vertebral canal dimensions are significantly different between normal and CSM-affected GDs. Absolute vertebral canal stenosis and severe foraminal stenosis involving the cervical vertebrae distinguish CSM-affected from clinically normal GDs. These findings are relevant to the pathogenesis of osseous-associated CSM and should be taken into consideration when performing imaging studies and planning surgery.

Cytokine concentrations in the cerebrospinal fluid of great danes with cervical spondylomyelopathy.

BACKGROUND: Chronic inflammation is involved in the pathogenesis of human cervical spondylotic myelopathy and could also play a role in cervical spondylomyelopathy (CSM) in dogs. HYPOTHESIS/OBJECTIVES: That cerebrospinal fluid (CSF) cytokine concentrations would differ between clinically normal (control) and CSM-affected Great Danes (GDs), with affected GDs showing higher levels of inflammatory cytokines, such as interleukin (IL)-6 and monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2). ANIMALS: Client-owned GDs: 15 control, 15 CSM-affected. METHODS: Prospective study. Dogs underwent cervical vertebral column magnetic resonance imaging and collection of CSF from the cerebellomedullary cistern. Cytokine concentrations were measured using a commercially available canine multiplex immunoassay. Cytokine concentrations were compared between groups. Associations with the administration of anti-inflammatory medications, disease duration and severity, severity of spinal cord (SC) compression, and SC signal changes were investigated in affected GDs. RESULTS: Affected GDs had significantly lower MCP-1/CCL2 (mean 138.03 pg/mL, 95% confidence interval [CI] = 114.85-161.20) than control GDs (212.89 pg/mL, 95% CI = 165.68-260.11, P = .028). In affected GDs, MCP-1/CCL2 concentrations correlated inversely with the severity of SC compression. There were no associations with administration of anti-inflammatory medications, disease duration, or disease severity. IL-6 concentrations were significantly higher (2.20 pg/mL, 95% CI = 1.92-2.47, P < .001) in GDs with SC signal changes. CONCLUSIONS AND CLINICAL IMPORTANCE: Lower MCP-1/CCL2 in CSM-affected GDs might compromise clearance of axonal and myelin debris, delay axon regeneration, and affect recovery. Higher IL-6 in CSM-affected GDs with SC signal changes suggests more severe inflammation in this group.

Transcranial magnetic motor evoked potentials in Great Danes with and without clinical signs of cervical spondylomyelopathy: association with neurological findings and magnetic resonance imaging.

Transcranial magnetic motor evoked potentials (TMMEPs) assess the functional integrity of the descending motor pathways, which are typically compromised in canine cervical spondylomyelopathy (CSM). The objective of this prospective study was to establish the reference ranges of TMMEP latency and amplitude in clinically normal (control) Great Danes (GDs), compare TMMEPs obtained in GDs with and without CSM, and determine whether there is any association between TMMEP data and severity of neurological signs or magnetic resonance imaging (MRI) findings. Twenty-nine client-owned GDs were enrolled (15 controls, 14 CSM-affected). All dogs underwent TMMEPs under sedation, and latencies and amplitudes were recorded from the extensor carpi radialis (ECR) and cranial tibial (CT) muscles. MRI of the cervical vertebral column was performed to evaluate the presence and severity of spinal cord (SC) compression, and the presence of SC signal changes. ECR and CT latencies were significantly longer in CSM-affected than control GDs. No significant differences between groups were found for amplitudes or neuronal path lengths. For the CT TMMEPs, CSM-affected GDs with moderate and severe clinical signs had significantly longer latencies than those with mild clinical signs. Significantly longer CT latencies were found in dogs with moderate and severe SC compression compared with dogs with mild compression. CT TMMEPs could not be recorded in 7/9 CSM-affected GDs with SC signal changes. These results provide a reference range for TMMEPs of clinically normal GDs. The use of TMMEPs is a valid ancillary test to assess the integrity of motor pathways in GDs with CSM.

Liver transplantation for type Ib glycogenosis with reversal of cyclic neutropenia.

We describe a case of glycogen storage disease type Ib in 32-year old male patient with poor metabolic control in spite of medical and nutritional management and the use of recombinant granulocyte stimulating factor. Because of this, liver transplantation was considered as a definitive treatment. We comment on the metabolic results of liver transplantation performed, with reversal of hypoglycemia, hyperuricemia, hypertriglyceridemia and cyclic neutropenia, all of which persist 4 years post-transplant. In view of this case, we believe that liver transplantation is a feasible option to consider in patients with type Ib glycogenosis as a definitive therapeutic procedure.

[Effect of preconceptional metabolic control in the course of pregnancy in diabetic patients]. / Influencia del control metabólico preconcepcional en la evolución de la gestación de la paciente diabética.

BACKGROUND: We analysed the relationship between metabolic control parameters during the preconception stage and pregnancy outcome in diabetic patients. PATIENTS AND METHOD: We examined 69 diabetic patients who underwent a preconception control at the Diabetes and Pregnancy Unit between 1992-1998. At the end of the preconception care period, 50 women (72.6%) became pregnant. Eight out of them (16%) had an abortion. RESULTS: Women who had an abortion did not differ from those who had not an abortion with regard to HbA1c levels at the end of the preconception period, age, duration of diabetes, age at diagnosis,anti-thyroid antibodies or microvascular disease. Among 41 single age stations, fetal macrosomia was observed in 36.6% cases, neonatal hypoglycemia in 19.5% and major congenital malformations in one case. Average level of HbA1c was 7.6 +/- 1.3%and 6.5 +/- 0.7 at the beginning and at the end of the preconception period, respectively (p < 0.001). In the group with macrosomia,average HbA1c at the end of the preconception period was 6.8 +/- 0.66% as opposed to 6.3 +/- 0.7% for the non-macrosomic group (p < 0.05). A linear correlation was seen between HbA1c levels at the end of the preconception period and infant weight (r = 0,432; p = 0,014), birth weight ratio (r = 0,450; p = 0,009), and a morbidity score (r = 0,458;p = 0,007). CONCLUSIONS: A better metabolic control during the preconception period may contribute to lessen the risk of fetal macrosomia and neonatal morbidity.

Molecular scanning for mutations in the insulin receptor substrate-1 (IRS-1) gene in Mexican Americans with Type 2 diabetes mellitus.

BACKGROUND: Insulin receptor substrate-1 (IRS-1) is an endogenous substrate for the insulin receptor tyrosine kinase, which plays an important role in insulin signaling. Mutations in the IRS-1 gene are associated in some populations with obesity and Type 2 diabetes. METHODS: To determine whether variation in the IRS-1 gene contributes to genetic susceptibility to insulin resistance and Type 2 diabetes in Mexican Americans, the entire coding region of the IRS-1 gene was screened for variation in 31 unrelated subjects with Type 2 diabetes using single-stranded conformational polymorphism analysis (SSCP) and dideoxy sequence analysis. Variants encoding amino acid substitutions were genotyped in 27 unrelated nondiabetic Mexican Americans and in all family members of subjects containing these variants, and association analyses were performed. To trace the ancestral origins of the variants, Iberian Caucasians and Pima Indians were also genotyped. RESULTS: Eight single base changes were found: four silent polymorphisms and four missense mutations (Ala94Thr, Ala512Pro, Ser892Gly and Gly971Arg). Allele frequencies were 0.009, 0.017, 0.017 and 0.043, respectively. There were no significant associations of any of these variants with diabetes, glucose or insulin levels during an oral glucose tolerance test, or with body mass index (BMI) in Mexican American families except for a modest association between the Ala94Thr variant and decreased BMI (30.4 kg/m(2) vs 24.0 kg/m(2); p=0.035). None of these four missense mutations were detected in Pima Indians. In Iberian Caucasians, neither Ala94Thr nor Ser892Gly were detected, and Ala512Pro was detected in only 0/60 diabetic patients and 1/60 nondiabetic controls. Gly971Arg was relatively more common in Iberian Caucasians with 12/58 diabetic patients and 7/60 nondiabetic controls being heterozygous for this variant (p=0.21 for comparison between diabetic and nondiabetic subjects). CONCLUSIONS: Ala94Thr, Ala512Pro and Ser892Gly mutation are rare in the populations studied. Gly971Arg, is more common in Mexican Americans and Caucasians, but is not a major contributor to genetic susceptibility to Type 2 diabetes.

Early postpartum metabolic assessment in women with prior gestational diabetes.

OBJECTIVE: To present the results of early postpartum metabolic assessment in women with gestational diabetes mellitus (GDM), to determine predictive factors for subsequent diabetes, and to investigate the association of postpartum glucose tolerance with other components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: A total of 788 women were evaluated 3-6 months after a GDM pregnancy. A 75-g oral glucose tolerance test (OGTT) was performed. Cholesterol, HDL cholesterol, triglycerides, blood pressure, BMI, and body fat distribution were assessed. Clinical and obstetric history, baseline variables at the diagnosis of GDM, metabolic control during pregnancy, and index pregnancy outcome were compared in women with diabetes and women without diabetes (American Diabetes Association [ADA] criteria) after pregnancy. Multivariate logistic regression analysis was used to ascertain independent predictors of subsequent diabetes. Correlation coefficients were assessed between postpartum glucose tolerance and lipid levels, blood pressure, BMI, and body fat distribution. RESULTS: According to ADA criteria, 588 (74.6%) women were normal, 46 (5.8%) had impaired fasting glucose, 82 (10.4%) had impaired glucose tolerance, 29 (3.7%) had both impaired fasting glucose and impaired glucose tolerance, and 43 (5.4%) had diabetes. Prepregnancy obesity, recurrence of GDM, gestational age at diagnosis of GDM, glucose values in the 100-g OGTT, number of abnormal values in the 100-g OGTT, fasting C-peptide levels in pregnancy, C-peptide/glucose score in pregnancy, insulin requirement in pregnancy, 3rd trimester HbA1c levels, and macrosomia differed significantly in women with subsequent diabetes. Independent predictors of postpartum diabetes were prepregnancy obesity, C-peptide/glucose score during pregnancy, and the number of abnormal values in the 100-g diagnostic OGTT. The area under the postpartum glucose curve was positively associated with BMI, waist circumference, waist-to-hip ratio, triglycerides, and systolic and diastolic blood pressures. CONCLUSIONS: Low C-peptide/glucose score during pregnancy together with prepregnancy obesity and severity of GDM (number of abnormal values in the 100-g diagnostic OGTT) are independent predictors of subsequent diabetes. Our data suggest that regardless of obesity and severity of GDM, a beta-cell defect increases the risk of postpartum diabetes. The association of postpartum glucose tolerance with triglyceride levels, blood pressure, obesity, and regional distribution of body fat suggests that postpartum glucose intolerance anticipates a high-risk cardiovascular profile that comprises other risk factors besides diabetes.

[Preconceptional control in diabetic women]. / El control preconcepcional en la gestante diabética.

The experience of the Preconceptional Clinic developed in our hospital from 1992 to 1996 is here reported. Twenty-eight insulin-dependent diabetic patients underwent a preconceptional control (PCC). Pregnancy was obtained in 19 patients (2 miscarriages, 12 full pregnancies, and 5 pregnancies in course). A comparative case-control study was performed between the 12 patients undergoing PCC, who have completed their pregnancy, and other 12 prepregnant diabetic patients, controlled from the 7-12 weeks of pregnancy. HbA1c levels in the PCC group were lower, and no differences regarding fetal morbidity were observed. The presence of a severe congenital malformation in the PCC group, with normal periconceptional HbA1c levels, denotes the teratogenic influence of factors yet to be elucidated.

[The metabolic control of insulin-dependent diabetes mellitus and diabetic nephropathy]. / Control metabólico de la diabetes mellitus insulinodependiente y nefropatía diabética.

Long-term complications of Insulin Dependent Diabetes Mellitus (IDDM) have been associated with several risk factors, particularly the degree of metabolic control and evolution time of the disease. A study was conducted with 219 randomly selected patients with IDDM at our clinic; evolutive, clinical and analytical parameters were assessed and conventional or multiple insulin therapy was evaluated. The classification of glycated hemoglobin (Hb A1c) in quartiles demonstrated a relatively higher incidence of diabetic retinopathy and nephropathy in the upper quartiles versus the lower quartile (p < 0.05). Likewise, patients with multiple insulin therapy had lower retinopathy (24.5% vs. 50.6, p < 0.001) and nephropathy rates (12.9% vs. 26.6%, p < 0.05) compared with those following a conventional insulin therapy. The multivariate analysis showed a statistically significant regression model (p < 0.001) for microalbuminuria level in patients with no established nephropathy; in these patients, the evolution time of IDDM and their Hb A1c level showed a positive independent association, and the use of multiple insulin therapy was a protective factor. The regression analysis of microalbuminuria levels compared with glycated hemoglobin in patients with no established nephropathy showed a value for Hb A1c of 9% as a break-point; from this point upwards microalbuminuria levels increased more markedly. The multivariate analysis here presented can help identify the presence of microalbuminuria in the pathological range in patients with IDDM followed at a hospital clinic from feasible clinical variables (evolution time, glycated hemoglobin level, program of insulin therapy used) establishing a metabolic objective which helps prevent the development of this complication.

[Magnesium. New perspectives]. / Magnesio. Nuevas perspectivas.

We reviewed the literature on the Mg++ cation with special attention on the clinico-therapeutical, physiopathogenic, and biochemical aspects. We extended the survey to some pathologies such as cardiovascular diseases and diabetes mellitus, given our understanding that a deficiency of this ion may constitute a primary cardiovascular risk factor. The dissociation present between the levels of intracellular and serum Mg++ is shown, since it may invalidate results that follow. We place special emphasis on the necessity to treat certain pathologies with magnesium salts and to quantify, with successive studies, the amount to administer.

Effect of the infusion of p-Glu-His-Ala-OH, analog of the anorexigenic peptide, on the insulin response induced by intravenous glucose. Preliminary results with obese subjects.

The effect of the intravenous infusion of peptide p-Glu-His-Ala-OH, analog of the postulated anorexigenic peptide, on the insulinaemic response to an intravenous bolus of 20 g glucose was studied in 6 obese patients (body mass index 43.12 +/- 5.77 kg/m2). The infusion of the peptide reduced the insulinaemic response (p < 0.05) without modifying either the C-peptide or the glucose response. This decreased insulinaemic response is associated with a greater hepatic extraction of insulin (86.45 +/- 1.1% vs 82.1 +/- 1.2%; p 0.05), determined in terms of the molar ratio of the C-peptide to insulin) but not with a smaller pancreatic secretion (determined as C-peptide levels). Our results confirm that the infusion of the peptide increases the hepatic insulin extraction without its effect being mediated by any intestinal factor. Its therapeutic application remains to be determined.

Effect of weight loss on insulin sensitivity and cardiovascular risk factors in glucose tolerant and intolerant obese subjects.

We observed 170 obese patients during 55 weeks in order to study the influence of insulin resistance and insulin sensitivity on cardiovascular risk factors in such patients as well as the changes occurring on these subjects as a result of weight loss. At the beginning of the study, the patients were divided into two groups, according to the results of an oral glucose tolerance test (OGTT) performed with 75 g of glucose: Group A, glucose tolerant subjects (n = 81), Group B, glucose intolerant subjects (n = 89). Initially Group B patients showed higher values for fasting blood glucose, 2 h after OGTT, systolic and diastolic blood pressure, cholesterol, triglycerides and cholesterol/HDL-cholesterol ratio when compared to Group A patients (p less than 0.05). Fasting and 1 h-post glucose load serum insulin levels in both Group A and Group B patients were higher than those found out in non over-weight tolerant subjects, but there were no differences between both groups. The serum glucose descent slope after an insulin tolerance test (ITT) was lower for group B than for group A (p less than 0.05), whereas both groups demonstrated lower descent slopes than non overweight tolerant subjects (p less than 0.05). After a 55 weeks follow-up period, the patients in Group A had lost 4.6 +/- 0.7 kg and those in Group B 6.2 +/- 1.1 kg. In both groups, the values for SBP, DBP, FBG, triglycerides and cholesterol/HDL-cholesterol ratio had dropped significantly, with a rise in the HDL-cholesterol level.(ABSTRACT TRUNCATED AT 250 WORDS)

[Influence of diabetes mellitus in hospital emergencies]. / Influencia de la diabetes mellitus en la Urgencia Hospitalaria.

A study performed at the Internal Medicine Emergency Department of the General Hospital "La Paz" (Madrid) over a six month period is presented. Its goal was to check the problems of the diabetic patient at his entrance to the medical emergency. We review the emergency pathological causes and we established that vascular (32%) and acute metabolic (17%) alterations were the most common pathologies, both in insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients. We analyzed the acute metabolic alterations considering that they can be foreseeable with an adequate knowledge of the disease. We point out an aspect that to our knowledge is basic: the diabetological information-education of diabetic patients (only 5% had a good knowledge of the disease and, furthermore, only 18% declared to have received some diabetological information). We also highlight the overuse that diabetic patients do of the hospital emergency departments, as a consequence of the previously mentioned poor information received which also reflects the insufficient or inadequate medical assistance in Primary Care Centers.

Programme of education for obese patients. Preliminary results after one year.

We have evaluated the effects of a Programme of education for Obese Patients with a duration of 12 hours on weight loss and the modification of other indices for cardiovascular risk in 88 obese patients, during the first year of therapy. The BMI dropped from 33.1 +/- 0.2 Kg/m2 to 31.7 +/- 0.7 (p less than 0.01) and 30.9 +/- 0.7) (p less than 0.01) at 5 and 10 weeks respectively, stabilizing subsequently at 35 and at 55 weeks. This was accompanied by a decrease of the triglycerides levels (141 +/- 9 vs 111 +/- 6 mg/dl; p less than 0.01) and of the total cholesterol/HDL-cholesterol ratio (4.7 +/- 0.3 vs 4.2 +/- 0.12; p less than 0.05), as well as of the values for systolic blood pressure (143 +/- 3 vs 121 +/- 3 mm Hg; p less than 0.05) and diastolic blood pressure 81 +/- 2 vs 64 +/- 1 mm Hg; p less than 0.01) at the end of the study. In terms of OGTT, initially 23 patients were classified as diabetic (BMI 32 +/- 0.9 Kg/m2), 25 presented intolerance to carbohydrates (BMI 34.1 +/- 1.6 Kg/m2) and 40 were normal (BMI 33.2 +/- 1.2 Kg/m2). The weight loss in the first 5 weeks was less in patients with diabetes then in those with carbohydrate intolerance and in the normal patients (2.2 vs 3.7 vs 5.9 Kg; p less than 0.01). From the 10th week on no differences were recorded.(ABSTRACT TRUNCATED AT 250 WORDS)