Post-translational processing of thyrotropin-releasing hormone precursor in rat brain: identification of 3 novel peptides derived from pro TRH

The sequence of rat hypothalamic pro-thyrotropin releasing hormone, deduced by sequencing of cDNA, in addition to 5 TRH progenitor genitor sequences contains leader, trailer and 4 intervening sequences separated by paired basic amino acid sequences. We have developed radioimmunoassays to synthetic peptides corresponding to portions of these cryptic proTRH sequences and have used these assays to identify and partially characterize proTRH peptides, distinct from TRH, in extracts of rat brain. Two of these peptides correspond closely in size to one intervening sequence and the car☐y-terminal sequence of proTRH. Three other peptides correspond to the intact amino-terminal leader sequence and two peptides formed by a further cleavage of the leader sequence at an internal paired basic amino acid sequence.     

Immunological blockade of endogenous thyrotropin-releasing hormone impairs recovery from hyperglycemia in mice

Administration of antiserum to thyrotropin-releasing hormone (TRH) into the lateral cerebral ventricle of mice significantly attenuated recovery from hyperglycemia induced by treatment with 2-deoxyglucose but had no effect on the plasma glucose of saline-treated mice. TRH, injected centrally together with the anti-TRH antibody, reversed the effect of the antiserum and blocked the development of hyperglycemia. These findings suggest that activation of TRH neurons in the central nervous system may be a physiological event influencing recovery from hyperglycemia.     

Congratulation on World Journal of Gastroenterology

Dear Professor Lian-Sheng Ma, Professor Michael Hobsley and I have greatly enjoyed reading the account of all you have done towards the development of "The World Journal of Gastroenterology", as described in the article by Zhen-Xi Li in the November 21st. Issue of the Journal.     

Blood pressure in adults with short stature skeletal dysplasias

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.     

Computerized family practitioner committee records — a data base for general practitioners

In the primary care environment the role of preventive medicine is assuming increasing importance and general practitioners need accurate and up-to-date information about their practice population. Computerization of family practitioner committee registers should provide a readily accessible data base from which data about groups of patients within the practice area can easily be extracted. This paper describes a study carried out in Northumberland, which set out to establish the type of information which would be of interest to general practitioners and how it could be produced.

It was found that a data base holding only registration data was of limited value to general practitioners, although useful for identifying target groups for screening programmes and showing demographic trends within the practice. The doctors felt that the inclusion of medical data would make the register a far more effective resource.

     

The growth hormone response to apomorphine at 4 days postpartum in women with a history of major depression

We have examined the responsiveness of dopamine sensitive neurones in the postpartum period in woman with a history of major depression who are at high risk of experiencing a recurrence of illness in the postpartum period. Fourteen women were assessed at 36 weeks of pregnancy and during the 3 months following delivery, using the Schedule for Affective Disorders and Schizophrenia, including its change version. They were not depressed at initial assessment. Five of the 14 women went on to experience a postpartum relapse (2 major depressive disorder, 2 generalised anxiety disorder, 1 panic disorder). On the fourth day postpartum, ie before relapse, the growth hormone response to the dopamine agonist apomorphine was measured as an index of the functional state of hypothalamic dopamine D2 receptors. Women who subsequently relapsed had a significantly greater growth hormone response to apomorphine than those who remained well. This was particularly marked in women with anxiety/panic. The development of increased sensitivity of hypothalamic dopamine D2 receptors in the postpartum period appears to predict the onset of depressive and anxiety disorders.     

Hypochromic macrocytes: are they reticulocytes?

Automated full blood counters measuring the size and haemoglobin concentration of individual red cells by high and low angle light scatter can provide estimates of the percentage of cells which are abnormal in either or both of these variables. The hypothesis that an increase in the number of large cells with a reduced haemoglobin content ("hypochromic macrocytes") was indicative of a reticulocytosis was investigated. A correlation was shown between the percentage of hypochromic macrocytes and the reticulocyte count. This correlation was too weak to allow the actual reticulocyte percentage to be predicted from the percentage of hypochromic macrocytes. An increased percentage of hypochromic macrocytes, however, often indicates an increased reticulocyte count and thus serves to chart the haematologist to this possibility.     

Dichotically presented emotionally intoned words produce laterality differences as a function of localisation task

Two-syllable words (burden; furrow; mantle; ration) each spoken in happy, angry, sad, and neutral tones of voice were dichotically paired. For each presented word-pair, subjects were asked to localise ("left"; "right") or reject the presence of one pre-specified word on one block of trials and one pre-specified emotional tone on a second trial block. Right ear advantages (REAs) indicated by a superior hit rate averaging 9.6% were found for all words. Left ear advantages (LEAs) averaging 15.2% were obtained for emotional intonation, with additional evidence of differences between emotion categories. Results are discussed in terms of complementary hemispheric roles for linguistic and prosodic analysis.     

Randomized Controlled Trial of the Safety and Efficacy of Daptomycin versus Standard-of-Care Therapy for Management of Patients with Osteomyelitis Associated with Prosthetic Devices Undergoing Two-Stage Revision Arthroplasty

The prevalence of Staphylococcus aureus causing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 (16.0%) (daptomycin, 6 mg/kg) and 5 of 23 (21.7%) (daptomycin, 8 mg/kg) daptomycin-treated patients and 2 of 25 (8.0%) comparator patients. Adverse-event rates were similar among daptomycin and comparator groups. Among modified intent-to-treat patients at TOC, clinical success rates were 14 of 24 (58.3%) for 6 mg/kg daptomycin, 14 of 23 (60.9%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for the comparator. Overall microbiological success at TOC was 12 of 24 (50.0%) for 6 mg/kg daptomycin, 12 of 23 (52.2%) for 8 mg/kg daptomycin, and 8 of 21 (38.1%) for comparator patients. In conclusion, daptomycin at 6 and 8 mg/kg given for up to 6 weeks was safe and appeared to be effective in managing staphylococcal PJI using a 2-stage revision arthroplasty technique in a total of 49 patients.