Need for follow up in coeliac disease

The use of follow up studies was evaluated in 128 patients with coeliac disease during their first visit to a department for adults. The original diagnosis had been made in childhood in all patients. Fifty eight (45%) of the subjects were following a gluten free diet, 23 (18%) were following a gluten free diet but with occasional gluten consumption, and 47 (37%) had adopted an unrestricted, gluten containing diet for a mean of 11.2 years. There was no correlation in individual subjects between the presence of symptoms, biochemical and immunological abnormalities, severity of histological findings, and the amount of dietary gluten, despite the greater frequency of symptoms in the group following an unrestricted diet than in the other two groups. Short stature and epilepsy with cerebral calcifications only occurred in patients following an unrestricted diet. As only diagnosis based on two or three biopsy samples and regular follow up correlated positively with dietary compliance, it is suggested that a histologically confirmed diagnosis of coeliac disease and regular lifelong follow up are essential in the management of these patients.     

Pathological complications of non-survivors of newborn extracorporeal membrane oxygenation

The pathology was reviewed of the early deaths identified from the first 50 neonates treated with extracorporeal membrane oxygenation (ECMO) during its introduction to the UK. Fifteen neonates died during or shortly after ECMO between August 1989 and June 1992. Data on 12 are presented (three did not have a postmortem examination). The clinical diagnoses at referral for ECMO were as follows: persistent pulmonary hypertension of the newborn (six infants), primary congenital pneumonia (one infant), community acquired pneumonia (two infants), birth asphyxia (one infant), respiratory distress syndrome (one infant), and meconium aspiration syndrome (one infant). In our group, at necropsy, five had significant haemorrhage (three intracranial, one pulmonary, one pericardial and intraventricular). Three of five infants with evidence of haemorrhage also had signs of sepsis. Six infants had evidence at necropsy of systemic sepsis, five showed evidence of severe anoxic brain injury, and four infants had cerebellar haemorrhages. Three infants had evidence of myocardial ischaemia. It is difficult to discriminate between the relative influence of the primary diagnosis, the mode of treatment, and the severity of presentation in the genesis of this pathology. It is likely that the extent and severity of some of the findings represent a pathological progression that would have been interrupted by the death of the patient, had ECMO not been instituted.     

Human embryonic stem cell research and the Juvenile Diabetes Research Foundation International – a work in progress

Abstract:  The Juvenile Diabetes Research Foundation International (JDRF) was founded in 1970 by parents of children with juvenile diabetes to find a cure for diabetes and its complications through the support of research. The foundation was an early supporter of stem cell research, recognizing the promise of stem cells to quicken the pace of discovery for a cure for juvenile diabetes. The JDRF has committed considerable resources to supporting stem cell research in both the United States and abroad. In the United States, the organization has been an advocate on the state and national level for increased funding and for expansion of current federal policy restricting embryonic stem (ES) cell research.     

Amplification of cyclic AMP generation reveals agonistic effects of certain beta-adrenergic antagonists

Some beta-adrenergic receptor (beta AR) antagonists, in addition to blocking receptor-mediated responses, possess agonistic properties or intrinsic sympathomimetic activity (ISA). In this study we describe several techniques for amplification of cAMP levels as a measure of agonistic activity, and we apply these techniques to the study of beta AR antagonists with ISA. We show that 1) a variety of beta AR antagonists with ISA, including alprenolol and cyanopindolol, enhance cyclic AMP accumulation in S49 lymphoma cells if cells are also incubated with the diterpene forskolin; 2) beta AR blockers with ISA stimulate cAMP accumulation in the presence of a water-soluble analog of forskolin but not in the presence of 9,11-dideoxyforskolin (which does not activate adenylyl cyclase); 3) the potentiation by forskolin is not unique to S49 cells but is also observed in BC3H1 smooth muscle-derived cells; 4) stimulation of cAMP accumulation by beta-blockers with ISA occurs in S49 cells in three additional settings that do not involve the use of forskolin, after pretreatment with pertussis toxin to inactivate the inhibitory guanine nucleotide binding protein, after pretreatment with [D-Trp8]-somatostatin to sensitize adenylyl cyclase, and using a radioimmunoassay to quantitate levels of cellular cAMP. We conclude that beta AR antagonists with ISA can weakly stimulate intracellular cAMP accumulation, but this stimulation is not easily detected. Elevation of cAMP levels may account for the agonistic effects of these drugs or, at least provides a measure of stimulatory guanine nucleotide-binding protein activation by these compounds.     

Serum MBP immunoreactivity and immunoglobulin level as markers of tumour type

Summary Forty three patients, admitted to the department of Neurological Surgery for management of central nervous system tumours, were studied pre-operatively for serum myelin basic protein immunoreactivity as a marker of central nervous system lesion and for circulating immunoglobulins and complement (C₃) levels. Myelin basic protein concentration did not appear to correlate with tumour type or grade. Serum immunoglobulin levels were found to be within the normal range but the mean IgM level was significantly higher in the glioma group when compared with meningiomas.     

Differential response of hypertrophied rat hearts to various α1-adrenoceptor agonists

Summary— With respect to the heart, the prolonged existence of hypertension, both in man and in experimental animals is predominantly characterized by an increase in left ventricular myocardial mass. In this process, the autonomic nervous system plays an important role. Although endogenous catecholamine stimulation of the heart is mainly exerted via the β-adrenoceptors, in several mammalian species, the stimulation of cardiac α-adrenoceptors also mediates positive inotropic actions. We investigated the functional responses of isolated hypertrophied hearts taken from spontaneously hypertensive rats (SHR) and rats with an induced aortic stenosis (ASR) to various α₁-adrenoceptor agonists and compared them with those from age matched Wistar Kyoto (WKY) and "sham" operated controls. Accordingly, we studied the functional response to: methoxamine (α₁), cirazoline (α₁) and phenylephrine (α₁ > β₁). The inotropic response to the α₁-adrenoceptor agonists cirazoline and methoxamine proved to be significantly weaker in hypertrophied hearts from SHR and ASR than in non-hypertrophied hearts from WHY and "sham" operated controls ( p < 0.05). The inotropic response to phenylephrine remained intact in hypertrophied myocardial tissue. However, it was significantly reduced when the hearts were pre-treated with the intracellular Ca²⁺-antagonists ryanodine and TMB-8. These findings show that the mechanism of sarcolemmal Ca²⁺ release, activated by phenylephrine, is still intact in the hypertrophied myocardial cell. In conclusion, these data show that cardiac hypertrophy, be it of genetical or mechanical origin, leads to a reduced response of the isolated heart to α₁-adrenoceptor stimulation.     

Clinical Assessment of Gestational Age

There is disagreement among authors as to what criteria are most reliable in assessing postnatal fetal age. A comparison–for objectivity, accuracy, and frequency of use– of specific criteria was made using three independent examiners at different educational levels: a second-year medical student, a perinatal nurse practitioner, and a pediatrics resident. It was shown that trained examiners develop favorite criteria which differ among examiners and thus sacrifice accuracy; however, accurate assessment of fetal age can be accomplished by an examiner with minimum clinical knowledge.