Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.     

Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Atrial natriuretic peptide in the diagnosis of patent ductus arteriosus

The aim of this study was to measure plasma atrial natriuretic peptide in preterm infants with a patent ductus arteriosus before and after closure with indomethacin. Atrial natriuretic peptide was measured in 28 preterm infants with clinical and echocardiographic evidence of a patent ductus arteriosus and in eight preterm infants who did not develop clinical evidence of a patent ductus arteriosus. Plasma concentration of atrial natriuretic peptide was measured by radioimmunoassay. In 18 infants the patent ductus arteriosus closed after one course of indomethacin; atrial natriuretic peptide levels decreased from median 1240 pg/ml (range 201-5483 pg/ml) to 266 pg/ml (range 62-1108 pg/ml). In four infants the patent ductus arteriosus closed after two courses of indomethacin and two infants had surgical ligation after indomethacin treatment failed. The patent ductus arteriosus closed spontaneously in four infants (atrial natriuretic peptide median level 152 pg/ml, range 61-495 pg/ml). In the eight infants without patent ductus arteriosus, atrial natriuretic peptide level was median 224 pg/ml (range 38-876 pg/ml). Measurement of plasma atrial natriuretic peptide concentration has a role in predicting when indomethacin treatment is indicated.     

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.     

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.     

Development of an improved multi-pressure-sensor probe for recording muscle contraction in human intestine

We have developed an improved semiconductor recording probe for monitoring motility of the upper small intestine in humans. The probe consists of six ultraminiature silicon pressure sensors spaced 10 cm apart and encased in a flexible polyurethane sheath. The probe is small [2.67 mm (8F) diameter], is easily passed transnasally, and is tolerated by patients for prolonged recording periods (24–36 hr) with a minimum of discomfort. The initial semiconductor and catheter material were those designed for use in the cardiovascular system, but they proved to be easily damaged by gastric acid and enzymes. After improvement of this probe, we now have recordings from more than 100 patients for an approximate total of 6000 hr of recording time. The improved probe is a durable recording device that facilitates the investigation of motility of the small intestine in humans in health and disease.This study was supported by funds from the Medical Research Service of the Veterans Administration and by National Institutes of Health Clinical Research Center grant RR-82.