Clinical and biochemical features of muscle dysfunction in subclinical hypothyroidism

Alterations in muscle structure and function have been reported in overt hypothyroidism, with decreased activity of enzymes involved in anaerobic and oxidative glucose metabolism. To test whether similar changes in muscle energy metabolism are present in subclinical hypothyroidism (sHT), we studied 12 patients with sHT who complained of mild neuromuscular symptoms. The control group included 10 sex- and age-matched healthy volunteers. Skeletal muscle lactate and pyruvate production were determined in the resting state and during dynamic arm exercise. During exercise, blood lactate was significantly higher in sHT patients than in controls from the third exercise step onward (P = 0.02 at 30%, p = 0.008 at 40%, and P = 0.002 at 50% of maximal voluntary contraction). Moreover, the mean increment in blood lactate during exercise was positively related (r2 = 0.44; P = 0.02) to the duration of sHT, but not to serum levels of TSH, free T3, or free T4. No significant difference was found in blood pyruvate concentrations between the two groups at baseline or during exercise. Thus, the lactate/pyruvate ratio curve paralleled the lactate curve in patients as well as controls. We conclude that muscle energy metabolism is impaired in sHT in rough proportion to the known duration of the disease. Early L-T4 therapy may be useful not only to provide specific treatment for such metabolic changes, but also to avoid progression to frank hypothyroidism.     

Congenital hypothyroidism: clues to an early clinical diagnosis

Congenital hypothyroidism is clinically difficult to diagnose early in life. A review of the common signs and symptoms of this treatable disease is presented, and a case diagnosed on the third day of life is discussed. Until neonatal thyroid screening is generally available it behooves all physicians caring for newborns and young infants to have a high index of suspicion for this disease.     

Echocardiographic changes and alterations in lipid profile in cases of subclinical and overt hypothyroidism

Forty four patients (22 of overt hypothyroidism and 22 of subclinical hypothyroidism) and 11 controls underwent lipid profile evaluation and two dimensional echocardiography. Amongst the various parameters evaluated, mean Interventricular Septal (IVS) dimensions were significantly (p < 0.005) raised in overt hypothyroidism [IVS: end diastolic (ED) = 0.973 +/- 0.223 cm.; end systolic (ES) = 1.300 +/- 0.240 cm.] with respect to control group [IVS : ED = 0.747 +/- 0.118 cm.; ES = 1.073 +/- 0.173 cm.]. Mean Left Ventricular Posterior Wall (LVPW) thickness was also significantly (p < 0.005) raised in overt hypothyroidism [LVPW : ED = 0.944 +/- 0.200 cm.; ES = 1.350 +/- 0.243 cm.] in comparison with control group [LVPW : ED = 0.779 +/- 0.091 cm.; ES = 1.176 +/- 0.128 cm.]. Evidence of diastolic dysfunction was present in both subclinical (n = 2) and overt hypothyroidism (n = 6) while pericardial effusion was seen only in overt hypothyroidism (n = 10). Mean Serum cholesterol was significantly raised in both subclinical (192.13 +/- 47.40 mg%) (p < 0.05) and overt hypothyroidism (231.27 +/- 68.30 mg%) (p < 0.005) with respect to control group (157.63 +/- 37.69 mg%). In overt hypothyroid patients mean serum Triglyceride (235.59 +/- 137.53 mg%) (p < 0.05), LDL (126.09 +/- 54.99 mg%) (p < 0.05) and Apo-B (0.698 +/- 0.354 g/L) (p < 0.05) levels were significantly higher as compared to control group (serum triglyceride 165.45 +/- 49.15 mg%, LDL 88.72 +/- 38.75 mg%, Apo-B 0.474 +/- 0.176 g/L.     

Segmental reflex sympathetic dystrophy: clinical and scintigraphic criteria

Clinical and scintigraphic criteria are proposed for the diagnosis of segmental reflex sympathetic dystrophy. Eight patients met previously described clinical criteria for reflex sympathetic dystrophy with involvement limited to only a portion of the hand. The delayed phase of the three-phase radionuclide bone scan was found to be highly sensitive (100%) for this small group of patients. Consecutive bone scans (n = 127) performed during a 6-month period for a variety of upper extremity problems were reviewed, and a segmentally diffuse pattern of tracer uptake was found to be highly specific (98%) for segmental reflex sympathetic dystrophy. Recognition and documentation of a more localized form of reflex sympathetic dystrophy will allow earlier recognition and treatment, which is an important factor in a successful outcome for managing pain dysfunction disorders.     

10-Oximeguanacone, the first nitrogenated acetogenin derivative found to be a potent inhibitor of mitochondrial complex I

BACKGROUND: Several retrospective studies have claimed that extracorporeal photopheresis (ECP) prolongs survival in patients with erythrodermic cutaneous T-cell lymphoma. In a retrospective study of 44 patients with Sézary syndrome, we compared survival in patients treated with ECP with that of patients treated conventionally at the same institute. All patients had genotypic evidence of a peripheral blood T-cell clone. OBSERVATIONS: Twenty-nine patients received ECP (group 1); 15 patients did not receive ECP, 8 patients when ECP was available (group 2) and 7 before ECP was available (group 3). Forty-three of 44 patients received other conventional treatments. Median survival from diagnosis of Sézary syndrome was 39 months in group 1, 22 months in group 2, and 27.5 months in group 3 (Kaplan-Meier analysis). Cox regression analysis showed no significant difference between the 3 groups after correcting for age, sex, and initial Sézary cell count (hazard ratio, 0.56; 95% confidence interval, 0.26-1.17; P = .12). CONCLUSIONS: This study does not support the contention that ECP prolongs survival in patients with Sézary syndrome. The median survival in the ECP-treated group is considerably less than that reported in other published series, possibly because genotypic evidence of clonality in the peripheral blood was required for inclusion in this study. We believe that a randomized trial comparing ECP with standard chemotherapy is urgently needed.     

MELAS syndrome in a five year-old child: clinical, biological and genetic characteristics

BACKGROUND: MELAS syndrome is a rare mitochondrial cytopathy; its diagnosis can be difficult. CASE REPORT: A 6-month-old boy presented with febrile seizures, possibly due to viral meningitis. At 7 months, he developed myoclonia and "brain attacks" and, subsequently, myoclonical attacks, regression of psychomotor and mental acquisitions, and progressive visual loss. The ratio of lactatorachia/lactacidemia was increased. The molecular genetic analysis showed an heteroplasmic point mutation with A-to-G mutation at nucleotide 3243 of the mitochondrial tRNA(leu) (UUR) gene. He was the second child of a mother having frequent headaches. His great aunt, a sister of his maternal grandmother, was mentally retarded and had frequent epileptic seizures and hemiparesy since her childhood. CONCLUSION: Any unusual neurological symptom, particularly when combined with "illegitimate" symptoms, should lead to search for a mitochondrial cytopathy.     

Simultaneously found transient hypothyroidism due to Hashimoto's thyroiditis, autoimmune hepatitis and isolated ACTH deficiency after cessation of glucocorticoid administration

We present a 42-year-old woman with concomitant transient hypothyroidism due to Hashimoto's thyroiditis, autoimmune hepatitis and isolated ACTH deficiency. Two months after ceasing prednisolone (5 mg/day) for uveitis, she was discovered incidentally to have liver dysfunction with hypergammaglobulinemia, later diagnosed as autoimmune hepatitis by histological examination of the biopsied liver. In addition, primary hypothyroidism due to Hashimoto's thyroiditis and secondary hypocortisolism due to isolated ACTH deficiency were revealed by endocrinological examination. Although not treated, her liver dysfunction and hypothyroid state recovered simultaneously, and the isolated ACTH deficiency was restored six months later. We concluded, after a needle-biopsy of the thyroid, that the transient hypothyroidism was due to Hashimoto's thyroiditis and the reversible ACTH deficiency was probably due to autoimmune hypophysitis. This case shows that cessation of steroid treatment may transiently exacerbate the polyglandular autoimmune syndrome.     

Premature peripheral vascular disease: clinical profile and abnormal lipid peroxidation

Type 2 diabetes is extremely common and increasing in the United States. The pathophysiology of type 2 diabetes is a combination of increased insulin resistance and inadequate secretion. The main risk factors for diabetes are family history, obesity, sedentary lifestyle, ethnic background, age, and a history of gestational diabetes. Diet and exercise, the cornerstones of diabetes management, will improve insulin sensitivity and indirectly augment insulin secretion. Until recently, the only pharmacological approaches to diabetes were sulfonylureas and insulin, which either augment insulin secretion or replace insulin, thus acting only on the insulin side of the equation. Recently, a series of new drugs have become available that are capable of decreasing hepatic glucose output (metformin), slowing postprandial glucose absorption (acarbose), and improving peripheral insulin sensitivity (troglitazone). With these drugs, either alone or in combination, and behavioral therapies, it is now feasible to achieve good to outstanding glycemic control in most individuals with type 2 diabetes.     

Heart rate variability index in congestive heart failure: relation to clinical variables and prognosis

AIM: To evaluate the clinical and prognostic value of the heart rate variability index in patients with congestive heart failure. METHODS: Sixty-four patients with chronic congestive heart failure and sinus rhythm underwent clinical assessment, 24-h ambulatory electrocardiography and echocardiography. Patients were followed for 6 to 30 months. Cardiac death or heart transplantation constituted the primary end-point of the study. RESULTS: The heart rate variability index was related to left ventricular ejection fraction (r=0.29, P=0.02) and New York Heart Association class (P=0.01). Patients with a restrictive left ventricular filling pattern had a lower heart rate variability index compared to patients with a non-restrictive pattern (26+/-11 vs 33+/-9 units, P=0.01). Patients who died (n=11) or underwent heart transplantation (n=4) had a lower heart rate variability index compared to survivors (21+/-10 vs 33+/-9 units, P<0.0001). In multivariate survival analysis, a reduced heart rate variability index was related to survival independent of parameters of left ventricular function. CONCLUSION: The heart rate variability index provides independent information on clinical status and prognosis in patients with chronic congestive heart failure.     

Acetone in urine as biological index of occupational exposure to isopropyl alcohol

To analyze whether HLA may be a determinant of the risk of developing cervical cancer precursor lesions, the association between HLA and cervical neoplasia among HPV16-seropositive and -negative subjects was determined in a population-based cohort in the V?sterbotten county of Northern Sweden. HLA genotyping of DR and DQ was done by PCR in 74 patients and 164 healthy controls matched for age, sex and area of residence. The presence of DQA1*0102 was weakly associated with cervical neoplasia in HPV16-seropositive patients. DQB1*0602 was weakly associated with disease in all patients, but was strongly increased among HPV16-seropositive patients compared to HPV16-seropositive controls. DR15 had an association with disease that was particularly strong among HPV16-seropositive subjects. The haplotype DQA1*0102-DQB1*0602 (DQ6) was also weakly associated with disease in all patients and significantly increased among HPV16-positive patients when compared to HPV16-positive controls. A similar association was seen when analysis was restricted to CIN 2-3 patients. DQA1*0501-DQB1*0301 (DQ7) was more common among HPV16-negative patients than among HPV16-negative controls and was also more common among HPV16-negative patients than among HPV16-positive patients. In conclusion, DQA1*0102-DQB1*0602 (DQ6) is associated with an increased risk of cervical neoplasia among HPV16-seropositive subjects and DQA1*0501-DQB1*0301 (DQ7) with an increased risk among HPV16-seronegative subjects.     

Cystic fibrosis screening: a fetus with hyperechogenic bowel may be the index case

BACKGROUND: The potential of hyperechogenic fetal bowel to act as a hallmark for prenatal cystic fibrosis screening in the general population is controversial. METHODS: Our goal was to evaluate the incidence of cystic fibrosis in 209 fetuses with hyperechogenic bowel diagnosed at routine ultrasonography and with no family history of cystic fibrosis. The diagnosis of cystic fibrosis was based on prenatal screening for the eight mutations most frequently observed in France (deltaF508, deltaI507, 1717-1G-->A, G542X, G551D, R553X, W1282X, N1303K) and at postnatal follow up. RESULTS: The overall incidence of cystic fibrosis was 7/209 (3.3%) which is 84 times the estimated risk of CF in the general population (112500). Of these seven cases, six were diagnosed prenatally based on DNA analysis (deltaF508/deltaF508, n=5; deltaF508/G542X, n=1). One case in which only one mutation had been recognised was diagnosed clinically after birth (deltaF508/unidentified mutation). Of the seven cases, none was diagnosed at 16-19 weeks, four at 16-24 weeks, and three after this. The incidence of heterozygous fetuses (15/209, 7%) was not significantly higher than the 5% expected in the general population. The mutations involved in these heterozygous cases were deltaF508 (n=13), G542X (n=1), and G551D (n=1). CONCLUSIONS: Screening for cystic fibrosis should be offered to families in which fetal hyperechogenic bowel is diagnosed at routine ultrasonography. This underlines the need to review genetic counselling in this situation where the fetus is the index case for a genetic disease.     

Resistance to macrolide antibiotics found in methicillin-resistant Japanese clinical isolates of Staphylococcus aureus in 1996

OBJECTIVE: To study the effect of sufficient energy intake, by means of the protocolized administration of naso-gastric tube feeding, on the nutritional status of a child with cancer. DESIGN: A comparative experimental study. SETTING: Tertiary care at the Centre for Pediatric Oncology, South East Netherlands, University Hospital, Nijmegen. SUBJECTS: Seven children, newly diagnosed with cancer, were included in the experimental study and all completed the trial period. Fourteen patients were included in the retrospective study. They were randomly chosen from a group of patients previously treated for a malignancy at our department and who had received naso-gastric tube feeding for at least 16 weeks. INTERVENTION: Protocolized (experimental group) vs non-protocolized (retrospective group) administration of naso-gastric tube feeding over a period of 16 weeks. The main difference was the amount of tube feeding administered. In addition to energy from other foods, children in the experimental group received 106+/-13% of their total daily energy requirements (TDER) by means of tube feeding, whereas children in the retrospective group had received 75+/-24%. MAIN OUTCOME MEASURES: Weight as a percentage of weight for height according to the 50th percentile of a healthy reference population=ideal weight. RESULTS: Weight, expressed as a percentage of the ideal weight, increased significantly in the experimental group (18.2 8.4; P=0.01) and the retrospective study group (5.2 7.3; P=0.001). However, the increase was statistically significant in favour of the experimental group (P=0.003), in which all the children reached their ideal weight, compared to 21% in the retrospective group. CONCLUSION: Aggressive protocolized nutritional intervention during the intensive phase of anti-cancer treatment, in the form of naso-gastric tube feeding that provides the child's total daily energy requirements, results in considerable improvement in the nutritional status.     

Illusory correlation in clinical judgment: Effects of amount of information to be processed.

Investigated the relationship between the amount of information to be processed in a judgment task and the reporting of illusory correlations. 130 undergraduate judges were assigned to 1 of 4 groups that differed in information-processing loads. Ss' reports of cue clinical problem relationships on the judgment task (Draw-A-Person test drawings) were evaluated for correct observations and for illusory correlations. As predicted, correct observations decreased and reports of illusory correlation increased as the information-processing load increased. (2 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)