Biomarkers predicting the controller dose of omalizumab in patients with chronic spontaneous urticaria.

BACKGROUND: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response. METHODS: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer. RESULTS: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/µL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients. CONCLUSIONS: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients.

Dysregulated microRNAs involved in contrast-induced acute kidney injury in rat and human.

BACKGROUND: Contrast-induced nephropathy (CIN) is a complex syndrome of acute nephropathy that occurs following infusion of intravascular contrast agents, and is associated with an increased risk for adverse cardiovascular events. While there is no ideal biomarker for making an early diagnosis of CIN, we hypothesized that levels of specific circulating microRNA (miRNA) species might serve such a role. METHODS: miRNA microarray assays were used to detect miRNAs in the kidney tissue of rats studied as an animal model of CIN. Real-time PCR was performed to validate results of the microarray assays. Kidney-enriched miRNAs detected in rat plasma were used as biomarkers to screen for CIN. Results obtained from the rat model of CIN were further validated in human patients with CIN. RESULTS: Fifty-one miRNAs were aberrantly expressed in the kidney tissues between CIN and control rats; and among these, 17 miRNAs showed a >2-fold change of expression in the kidney tissues of CIN rats when compared with their expressions in non-CIN control rats. Among the 17 miRNAs aberrantly-expressed miRNAs screened from kidney tissue, only six also showed significantly different expression in the plasma of CIN rats. When compared with their levels in non-CIN control rats, the levels of three miR-30 family members (miR-30a, miR-30c, and miR-30e), as well as miR-320, were significantly increased in the plasma of CIN rats, while the plasma levels of miRNAs let-7a and miR-200a were significantly decreased. In a validation study of these results conducted with human plasma samples, only miR-30a, miR-30c, and miR-30e showed > 2-fold increases in CIN patients when compared with non-CIN patients. Receiver operating curves constructed to examine the abilities of miR-30a, miR-30c, and miR-30e to discriminate CIN patients from non-CIN patients showed AUCs of 0.954, 0.888, and 0.835, respectively. CONCLUSIONS: Our study provides the first evidence that plasma miRNAs, and especially three miR-30 family members (miR-30a, miR-30c, and miR-30e), might serve as early biomarkers and (or) target candidates for CIN.

Trimethylamine N-oxide levels are associated with NASH in obese subjects with type 2 diabetes.

AIMS: Trimethylamine N-oxide (TMAO), choline and betaine serum levels have been associated with metabolic diseases including type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD). These associations could be mediated by insulin resistance. However, the relationships among these metabolites, insulin resistance and NAFLD have not been thoroughly investigated. Moreover, it has recently been suggested that TMAO could play a role in NAFLD by altering bile acid metabolism. We examined the association between circulating TMAO, choline and betaine levels and NAFLD in obese subjects. METHODS: Serum TMAO, choline, betaine and bile acid levels were measured in 357 Mexican obese patients with different grades of NAFLD as determined by liver histology. Associations of NAFLD with TMAO, choline and betaine levels were tested. Moreover, association of TMAO levels with non-alcoholic steatohepatitis (NASH) was tested separately in patients with and without T2D. RESULTS: TMAO and choline levels were significantly associated with NAFLD histologic features and NASH risk. While increased serum TMAO levels were significantly associated with NASH in patients with T2D, in non-T2D subjects this association lost significance after adjusting for sex, BMI and HOMA2-IR. Moreover, circulating secondary bile acids were associated both with increased TMAO levels and NASH. CONCLUSIONS: In obese patients, circulating TMAO levels were associated with NASH mainly in the presence of T2D. Functional studies are required to evaluate the role of insulin resistance and T2D in this association, both highly prevalent in NASH patients.

Laparoscopic adrenalectomy: lessons learned from an initial series of 100 patients.

BACKGROUND: Laparoscopic adrenalectomy is considered the gold standard for the surgical treatment of adrenal disorders in most centers. This study analyzes the authors' experience using the lateral intraperitoneal approach with the first 100 patients. In addition to analyzing the authors' experience, this article aims to contrast it with some published series as an internal quality control. METHODS: In a 10-year period, 138 laparoscopic adrenalectomies were performed for 100 patients. Demographics, surgical results, complications, and long-term outcomes were analyzed. RESULTS: The participants comprised 69 women and 31 men with a mean age of 37 years. The procedures included 24 right, 38 left, and 38 bilateral adrenalectomies. The indications for surgery were Cushing's disease for 33 patients, pheochromocytoma (4 bilateral) for 23 patients, Cushing's syndrome for 18 patients, Conn's syndrome for 16 patients, and incidentaloma for 10 patients. Five procedures were converted to open surgery. Two patients with pheochromocytoma required intraoperative blood transfusion. The mean operative time was 174 min for unilateral adrenalectomies and 302 min for the bilateral procedures. The mean hospital stay was 5 days. Surgical morbidity included an abdominal wall hematoma, a small pneumothorax, and intraabominal bleeding in one patient that required reexploration. There were three operative mortalities not related to the technique. The long-term results showed control of hypercortisolism in all the patients with Cushing's disease and 82% of the patients with pheochromocytoma. Most of the patients with Conn's syndrome (91.4%) became normotensive after surgery. CONCLUSIONS: Laparoscopic adrenalectomy is safe and effective. The complications are mild, and mortality is related more to the patient's condition than to the surgical technique.

Functional Outcomes 18 Months After Total and Midarm Transplantation: A Case Report.

BACKGROUND: The function reported after arm transplantation is deemed beneficial relative to the marked disability that upper arm amputation causes. OBJECTIVE: We report a 51-year-old man with a Disabilities of the Arm, Shoulder and Hand (DASH) score of 75.83 who underwent bilateral arm transplantation in October 2015. PROCEDURE: The right arm was transplanted at the glenohumeral joint level, including transplantation of the humeral head, joint capsule, and rotator cuff ligaments and tendons. Additionally, neurorrhaphies were performed at the origin of the terminal branches of the brachial plexus, including the axillary and musculocutaneous nerves. Therefore, this was considered a total arm transplantation. The left arm was transplanted at the transhumeral level, with complete transplantation of the biceps and triceps brachii, and terminolateral neurorrhaphy of the donor musculocutaneous nerve to the receptor radial nerve. A maintenance triple immunosuppression scheme was administered, with tacrolimus levels kept at 10 ng/mL. RESULTS: At 18 months post-transplantation, the intrinsic musculature in the left hand showed electrical registry, DASH score was 67.5, Carroll test score was 28 in both extremities, Hand Transplant Score System was 67.5 in the right extremity and 77.5 in the left extremity, and Short Form-36 score was 96.1. The patient was healthy, with restored body integrity. He could lift medium-sized weightless objects, eat and go to the bathroom by himself, drink liquids with bimanual grasp, swim, dress almost independently, and drive. CONCLUSION: The functional evolution of the patient was similar to previously reported transplanted arms, even though the right arm transplant involved the glenohumeral joint and axillary and musculocutaneous nerve repair.

Infundibulo-hypophysitis-like radiological image in a patient with pituitary infiltration of a diffuse large B-cell non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is a hematological tumor caused by abnormal lymphoid proliferation. NHL can arise in any part of the body, including central nervous system (CNS). However, pituitary involvement is a quite rare presentation. The diffuse large B-cell lymphoma (DLBCL) is the most common subtype when pituitary is infiltrated. Here, we report a case of pituitary infiltration of NHL DLBCL type in a woman with hypopituitarism and an infundibulum-hypophysitis-like image on magnetic resonance imaging (MRI). A female aged 64 years, complained of dyspepsia, fatigue, weight loss and urine volume increment with thirst. Endoscopy and gastric biopsy confirmed diffuse large B-cell lymphoma. Treatment with chemotherapy using R-CHOP was initiated. During her hospitalization, hypotension and polyuria were confirmed. Hormonal evaluation was compatible with central diabetes insipidus and hypopituitarism. Simple T1 sequence of MRI showed thickening of the infundibular stalk with homogeneous enhancement. After lumbar puncture analysis, CNS infiltration was confirmed showing positive atypical lymphocytes. Pituitary and infundibular stalk size normalized after R-CHOP chemotherapy treatment. In conclusion, pituitary infiltration of NHL with infundibular-hypophysitis-like image on MRI is a rare finding. Clinical picture included hypopituitarism and central diabetes insipidus. Diagnosis should be suspected after biochemical analysis and MRI results. Treatment consists of chemotherapy against NHL and hormonal replacement for pituitary dysfunction. LEARNING POINTS: Pituitary infiltration by lymphoma can present with signs and symptoms of panhypopituitarism and diabetes insipidus.MRI findings can resemble an autoimmune hypophysitis.Patients can recover pituitary function as well as normalization of MRI after chemotherapy treatment.

Lack of agreement between the World Health Organization Category of impaired glucose tolerance and the American Diabetes Association category of impaired fasting glucose.

OBJECTIVE: To study the concordance between the 1997 American Diabetes Association (ADA) impaired fasting glucose (IFG) category with the World Health Organization (WHO) impaired glucose tolerance (IGT) status in a population with a high prevalence of diabetes. RESEARCH DESIGN AND METHODS: We analyzed the oral glucose tolerance tests (OGTTs) carried out at the Instituto Nacional de la Nutrición Salvador Zubiran (INNSZ) central laboratory from June to December 1997. We included patients with fasting plasma glucose (FPG) between 60 and 160 mg/dl. The results from the glucose tolerance test were selected as the gold standard. RESULTS: Among the 1,802 glucose tolerance test results available for analysis, 1,706 fulfilled the requirements to be included. Diabetes and IGT were remarkably more frequently diagnosed when the WHO criteria were applied. The new ADA criteria failed to diagnose 69% of WHO diabetic patients and the vast majority of WHO glucose-intolerant subjects. Using the new criteria, 82% were considered normal. Of the IFG subjects, 39% were classified as diabetic and 23% were normal according to the 2-h postchallenge glucose values. Only 37% of the IFG patients were, in fact, glucose intolerant according to the WHO criteria. CONCLUSIONS: Our results clearly show that the 1997 ADA criteria are less sensitive for diagnosing diabetes than OGTT-based WHO criteria. Even more important, there is poor agreement between the WHO category of IGT and the ADA category of IFG.

Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.

The apolipoprotein E4 allele is not associated with an abnormal lipid profile in a Native American population following its traditional lifestyle.

The apolipoprotein E4 allele is associated in industrialized countries with an elevated LDL cholesterol concentration and an increased cardiovascular risk. Our purpose in this study was to assess the influence of the genetic variation at the APOE gene locus on the lipid profile of a Native American rural population. We examined plasma lipid levels and the common apo E alleles in 142 healthy randomly selected adults living in their native communities in western Mexico. Their age was 38+/-17 years and the BMI 25.7+/-4.5 kg/m2. Plasma cholesterol, triglycerides, LDL C and HDL C were 165+/-29.6, 126+/-83, 98+/-26 and 42+/-12.7 mg/dl respectively. Ninety-one per cent of the subjects had Lp(a) concentrations below 20 mg/dl and 30% had levels lower than 2 mg/dl. The most common APOE genotype was E3/3 (63%), followed by E3/4 (30.1%). The prevalence of the E2 allele was very low (2.3%). No difference was observed in LDL C concentrations between the E3/E3 and E3/E4 subjects; however carriers of the E2/3 genotype had lower LDL C levels. Similar results were obtained for cholesterol and apo B levels. In summary, the increased LDL C levels associated with the E4 allele in previous studies were not observed in a population with non-westernized habits. Environmental factors, such as diet and lifestyle, could outweigh the hypercholesterolemic predisposition resulting from the presence of the apo E4 allele.

Efficacy and safety of atorvastatin in hyperlipidemic, type 2 diabetic patients. A 34-week, multicenter, open-label study.

Hyperlipidemia is common in type 2 diabetic patients and is an independent risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of once-daily atorvastatin 10-80 mg for the treatment of hyperlipidemia in type 2 diabetics with plasma low-density lipoprotein cholesterol (LDL-C) levels exceeding 3.4 mmol/l (130 mg/dl). One hundred and two patients met the study criteria and received 10 mg/day atorvastatin. Patients who reached the target LDL-C level of

The prevalence of diabetes and associated coronary risk factors in urban and rural older Mexican populations.

OBJECTIVE: To determine the prevalence of diabetes and examine its association with food intake, anthropometric and metabolic variables, and other coronary risk factors in urban and rural older Mexican populations. DESIGN: A cross-sectional study. SETTING: Three Mexican communities (urban areas of medium and low income and a rural area). PARTICIPANTS: A total of 121 men and 223 women aged 60 years and older and 93 men and 180 women aged 35 to 59 years were selected randomly for inclusion in the survey, which was derived from the CRONOS study (Cross-Cultural Research on Nutrition in the Older Adult Study Group) promoted by the European Economic Community. MEASUREMENTS: A personal interview assessed demographic information, personal medical history, and functional status, and a 24-hour diet recall was obtained. A physical examination included anthropometric and blood pressure measurements. A fasting blood sample was obtained for measurements of lipids, insulin, and glucose. RESULTS: Diabetes prevalence was higher in men than in women for all age groups: 16.7% versus 9.5% in younger adults and 30.8% versus 22.8% in older adults. For all age groups, diabetes was more highly prevalent in urban communities. Using a multivariate stepwise logistic regression, variables associated independently with diabetes in older individuals were: gender (male sex: OR = 2.1; P < .009); diminished carbohydrate intake in the diet (OR = 0.77; P < .03); central distribution of adiposity (OR = 1.9; P < .03); and functional disability (OR = 2.3; P < .01). This relationship was not observed with living area, income, education, fiber and alcohol intake, body mass index, or age. Individuals 80 years and older had a diminished atherogenic risk profile. Diabetes in older people was associated significantly with hypertriglyceridemia, impaired functional status, and an increased prevalence of ischemic heart disease; in younger adults diabetes was associated with low density lipoprotein (LDL) hypercholesterolemia, hypertriglyceridemia, and a proportionally higher fat intake. CONCLUSION: This survey confirms the high prevalence of diabetes in the older Mexican population - particularly in men and in individuals living in urban areas - associated with an increased prevalence of other coronary risk factors. Diabetes was associated with higher fat, low carbohydrate, low fiber diets and increased prevalence of central distribution of adiposity. In the older subjects, diabetes was associated significantly with hypertriglyceridemia, impaired functional status, and increased prevalence of ischemic heart disease. A bias produced by early mortality and a survivorship effect must be considered in studies of older individuals. The health situation in the older Mexican population presents a complex problem that needs correct diagnosis and better strategies to benefit those segments of the population at increased risk.

Lipids, apoprotein B, and associated coronary risk factors in urban and rural older Mexican populations.

The objective of this comparative cross-sectional study was to determine the prevalence of dyslipidemias and examine its association with food intake and metabolic variables in urban and rural elder Mexican populations. Three different communities (urban areas of medium and low income and a rural area) were studied. A total of 344 subjects aged 60 years and older and 273 aged 35 to 59 years were included. The evaluated parameters were personal medical data, 24-hour diet recall, and fasting plasma lipids, insulin, and glucose levels. Older subjects, especially men, living in the rural area had lower cholesterol levels (5.02 +/- 0.97 v 5.6 +/- 1.07 mmol/L; P <.05) and insulin levels (12 +/- 10 v 42 +/- 68 mU/mL) and higher high-density lipoprotein cholesterol concentrations (1.31 +/- 0.36 v 1.07 +/-0.28 mmol/L) than the elders from the urban medium-income group. Possible explanations for these differences are found in the dietary habits of the groups. Rural elders had higher amounts of fiber (20 +/- 11 v 10 +/- 6 g/d) and carbohydrate (70% +/- 0.08% v 52% +/- 0.11% of calories) and lower fat (18% +/- 0.07% v 33% +/- 0.1% of calories) in their diets. In the urban groups, low-density lipoprotein hypercholesterolemia was present in 17.8% of adult and 39.1% of elderly women (P =.00001). In conclusion, environmental factors still play a prominent role in the pathophysiology of the dyslipidemias in the elderly.

Ciprofibrate versus gemfibrozil in the treatment of mixed hyperlipidemias: an open-label, multicenter study.

Mixed hyperlipidemia is a common risk factor for cardiovascular disease. The aim of this trial was to evaluate the efficacy and safety of ciprofibrate versus gemfibrozil for the treatment of patients with mixed hyperlipidemia carefully selected for similar lipid profiles. A total of 68 patients who had mixed hyperlipidemia after following an isocaloric American Heart Association (AHA) phase I diet for 4 weeks were included. The plasma lipid levels at the inclusion were low-density lipoprotein-cholesterol (LDL-C) > or = 130 mg/dL, cholesterol > or = 240 mg/dL, and triglycerides > or = 200 mg/dL. Patients were randomly assigned to receive ciprofibrate 100 mg/d or gemfibrozil 1,200 mg/d. At the end of the 8-week treatment period, efficacy and safety parameters were compared with baseline values. The primary efficacy parameters of the study were percentage changes in triglycerides and LDL-C from baseline. After 8 weeks, plasma triglyceride concentrations were decreased by 43.5% and 54% compared with baseline during ciprofibrate and gemfibrozil therapy, respectively (P <.001). High-density lipoprotein-cholesterol (HDL-C) concentrations were increased 20.8% and 19.3% during ciprofibrate and gemfibrozil, respectively (P <.001). Apoprotein B, cholesterol, and very-low-density lipoprotein-cholesterol (VLDL-C) concentrations were also improved by the study drugs (18.6%, 13.2%, and 30.9%, respectively, during ciprofibrate and 44%, 13.8%, and 14.4%, respectively, during gemfibrozil). Meanwhile, the effect of the drug was minimal on LDL-C. A significant decrease in non-HDL-C resulted from both treatments (19% and 19.5%, respectively, P <.05). The only statistically significant difference observed between treatments was the effects on fibrinogen concentration, a coronary risk factor. Ciprofibrate significantly decreased its concentration by 18.8%, fibrinogen was slightly increased during gemfibrozil treatment. No patient had a significant modification on any of the safety tests. In summary, ciprofibrate and gemfibrozil are well-tolerated and efficacious treatments for mixed hyperlipidemia. Significant reductions in triglycerides, non-HDL-C, and apolipoprotein B were achieved with both drugs. A significant fibrinogen reduction was obtained with ciprofibrate.

Nortriptyline-fluphenazine vs. carbamazepine in the symptomatic treatment of diabetic neuropathy.

We compared the efficacy and tolerance of the combination of nortriptyline-fluphenazine (NF) vs. carbamazepine (CMZ) in the symptomatic therapy of patients with severe, distal, symmetrical, predominantly sensitive diabetic polyneuropathy (DPN). We followed a double blind, crossover, randomized and double placebo design. Sixteen patients with severe DPN participated in the study. Patients received either NF (1 tablet three times a day (tid)), for 2 weeks and 2 tablets tid for the next 2 weeks or CMZ 1/2 tablet tid for 2 weeks and 1 tablet tid for the next 2 weeks. After this, patients received placebos of both drugs (wash-out period), until symptoms returned to baseline levels (100%), then they were crossed over to receive the other comparing drug schedule. A visual analogue scale was used to evaluate the percent changes in pain and paresthesia. HbA1, fasting serum glucose, and safety tests were performed at 2- and 4-week intervals, respectively. Both therapies produced significant improvement of both pain and paresthesia. No statistically significant differences were observed between both therapies for either pain or paresthesia. No significant biochemical changes were observed with any of the two therapies. Side effects were mild and more frequent in the NF period. In this study no superiority of either drug schedule was demonstrated; therefore, the decision to use any of them should be made according to the associated pathology and potential side effects of each drug.

Diabetic ketoacidosis in adults: clinical and laboratory features.

In this retrospective study, we report the clinical and biochemical features of diabetic ketoacidosis (DKA) in adult patients who were managed at the Instituto Nacional de la Nutrición during a 6.5 year period. There were 98 episodes in 46 patients: 22 females (48%) and 24 males (52%). Six patients (13%) had four or more episodes of DKA. Thirty five percent of the events occurred in patients with IDDM; 48% in "late onset" NIDDM: 9% in "early onset" and 9% in classical NIDDM. Infections as the precipitating factor in 41% of episodes of DKA were the initial manifestation of diabetes. We compared our results with those from other reported series, finding no differences among them. The mean anion gap in our series was 30.4. Main complications identified were hypokalemia in five cases, hypoglycemia in four cases, hypernatremia in four cases, and acute pulmonary edema, ventricular fibrillation, neurological deficit and coma in one case each. There were three deaths (6.5%) in the whole group. To our knowledge, this is the largest series on adult patients with DKA reported in our country in the last decade. The obtained results may help evaluate prospectively the impact of different diagnostic and therapeutic strategies in the management of DKA.

Leukocyturia in women with diabetes and its clinical implications.

BACKGROUND: Urinalysis is one of the most common studies performed on the diabetic patient at every visit. The presence of leukocyturia is relatively common but it is not clear what the attitude of the physician toward this particular finding should be. The main objective of the present study was to investigate the clinical significance of leukocyturia in diabetic women. METHODS: Ninety-eight diabetic women (84.7% type 2) aged 57 +/- 13 years who were being seen at the diabetic out-patient clinic were randomly selected. All patients underwent a clinical and gynecologic examination and a urinalysis. A Papanicolaou smear and a urine culture were also obtained. RESULTS: The overall prevalence of leukocyturia (>5 cells/high power field (hpf)) was 46.5%. Patients with urinary tract infections (UTI) were 7.5 times more likely to have leukocyturia, while a leukocyte count <5cells/hpf predicted the absence of UTI in 96% of the women. In the comparison of patients with and without leukocyturia, we found that proteinuria (p = 0.06) and bacteriuria (p <0.002) were more common in the women with leukocyturia. A significant association with leukorrhea was not demonstrated. The empirical use of antibiotics was 12 times more frequent in the patients with leukocyturia. CONCLUSIONS: A urinary culture should be requested in all diabetic patients with leukocyturia. The possibility of a UTI is remote when leukocyturia is absent.

Hypopituitarism in two brothers born by breech delivery.

OBJECTIVE: To describe two brothers with hypopituitarism who had been born by breech delivery and to discuss whether this condition corresponds to a familial form or to a pituitary stalk section as a result of the breech delivery. METHODS: We present the clinical, biochemical, and magnetic resonance imaging (MRI) characteristics of two Mexican brothers, 19 and 21 years old, with hypopituitarism and a history of breech delivery. RESULTS: Physical examination of both patients showed short stature with normal body proportions, an obviously younger appearance than that expected for their chronologic age, high-pitched voice, irregularly positioned teeth, no axillary or pubic hair, and prepubertal genitalia. Biochemical testing showed low thyroxine and free thyroxine values with inadequate or normal thyrotropin, low basal testosterone, and mildly increased serum prolactin levels. Stimulation tests showed a normal and a delayed thyrotropin response to thyrotropin-releasing hormone, subnormal serum cortisol, considerably blunted growth hormone (GH) response to insulin-induced hypoglycemia, and absence of GH response to GH-releasing hormone in both cases. MRI showed an ectopic neuropituitary gland. In case 1, a caudal portion of a very thin pituitary stalk was observed, suggesting the preservation of a vascular component of the stalk. Because both parents of these brothers shared the major histocompatibility complex haplotype HLA-A*2301, B*3501, DRB1*0407, DQA1*03, DQB1*0201, consanguinity was suggested. CONCLUSION: The phenotype of these patients differs from that described in families with POU1F1 (Pit-1) and PROP1 mutations. These cases are most likely related to an autosomal recessive gene mutation that warrants further research. To our knowledge, this is the first report of hypopituitarism in two brothers born by breech delivery.

Effect of major improvement in glycemic control on results of cardiovascular function tests in patients with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the effect of major improvement in glycemic control on cardiovascular function tests in patients with insulin-dependent diabetes mellitus (IDDM). METHODS: Eight men with chronic, poorly controlled IDDM (serum fructosamine >300 mmol/L and mean fasting blood glucose >200 mg/dL), who were 24 +/- 6 years of age and had a mean duration of diabetes of 8 +/- 1 years, were studied. No patient had microalbuminuria, was taking medication other than insulin, or had evidence of heart disease. Patients underwent baseline continuous ambulatory blood pressure monitoring, echocardiographic studies, and cardiovascular autonomic function tests, which were repeated after 4 weeks of an intensified insulin treatment program (IITP), during which they reached and maintained blood glucose concentrations and serum fructosamine levels in near-normal, nondiabetic ranges. RESULTS: Substantial changes in glycemic control had no significant influence on results of ambulatory blood pressure monitoring, cardiovascular autonomic function tests, and echocardiographic studies. CONCLUSION: Major improvement in glycemic control during a 1-month period in patients with IDDM had no significant influence on cardiovascular function tests. We cannot exclude the possibility that, after a longer duration of an IITP or in patients with clinically evident heart disease or evidence of major complications of diabetes, different responses might be observed.

An ectopic adrenocorticotropic hormone syndrome caused by a sacrococcygeal chordoma: report of a case with a slow progression.

OBJECTIVE: To report the first case of an ectopic adrenocorticotropic hormone (ACTH) syndrome caused by a sacrococcygeal chordoma. METHODS: We present a case report with clinical, laboratory, and histologic details. RESULTS: A 76-year-old man was admitted to the hospital because of urinary obstruction. Five years previously, a urethral mass had been detected, and transurethral prostatectomy had been performed. Annual computed tomographic (CT) scans showed no change in size of the mass. In 1995, skin hyperpigmentation, central obesity, and bilateral edema were noted. The patient was admitted to the hospital in July 1996. A CT scan of the abdomen revealed a large mass close to the sacrum and compressing the bladder and rectum. Cortisol measurements (AM and PM) were 309 and 271 ng/mL, respectively. The plasma ACTH concentration was extremely elevated (3,125 pg/mL). Although resection of the mass was attempted, complete resection was not possible because the tumor had infiltrated the sacrum. Plasma cortisol concentrations in samples obtained 7 and 8 days postoperatively were normal. Plasma ACTH was substantially decreased (180 pg/mL) but remained above normal. The histologic features of the tumor were compatible with a chordoma. Neoplastic cells stained positively for ACTH. CONCLUSION: This report describes the first case of an ectopic ACTH syndrome caused by a sacrococcygeal chordoma. A slow progression of symptoms in an ectopic ACTH syndrome had been described only for carcinoid tumors. These data add a new entry to the list of neoplasms capable of causing this syndrome.

Diabetes knowledge and its determinants in a Mexican population.

PURPOSE: The purpose of this study was to measure the level of diabetes knowledge in a representative group of Mexican individuals with diabetes and to identify the factors that influence it. METHODS: A validated questionnaire was administered to 570 outpatients; 11.2% had Type 1 diabetes, 36.4% had Type 2 diabetes treated with insulin, and 52.2% had Type 2 diabetes treated with oral agents. Samples for HbA1c determination also were obtained. RESULTS: The percentage of correct answers in each section of the questionnaire was low. Type 1 patients had the highest scores, followed by the insulin-treated Type 2 patients; those with chronic complications also had high scores. Educational background, attendance at diabetes courses, age, and HbA1c concentration were the main predictors of knowledge. Attendance at courses was influenced by the severity of the disease. CONCLUSIONS: The amount of patient knowledge about diabetes-related issues was low in this representative Mexican population. The educational efforts were focused on those with the worst metabolic control and/or with diabetes complications.