Clinical research: where does it come from? Where is it going?

In this editorial the author examines briefly the past, present and future of clinical investigation in general and particularly in Switzerland, where the same problems are encountered as in other European countries and North America. The main problems reside in the fragmentation of internal medicine into subspecialities with their own separate meetings and journals, at the expense of multidisciplinary sources of information on medical progress, thus widening the gap between the practitioners and the scientific community. Through examples, it is pointed out that the progression of medical knowledge follows the path from basic research in biochemistry, cellular biology, animal experiments, clinical investigation and finally clinical medicine not unidirectionally but bidirectionally. Thanks to the Swiss National Science Foundation, the Medical Schools of the five Universities and many private foundations, a considerable effort has been made in past decades to foster basic and clinical research, resulting in a most favorable position for our country on the international scene. There is a fear that political and administrative decision could jeopardize the present situation and imperil the future. Finally, citing Osler from his work "Aequanimitas", the author stresses that "the true test of a nation's life... is to be found in its intellectual and moral standards", and that "the measure of the value of a nation to the world is neither the bushel nor the barrel, but mind".     

A novel point mutation in the translation initiation codon of the pre-pro-vasopressin-neurophysin II gene: cosegregation with morphological abnormalities and clinical symptoms in autosomal dominant neurohypophyseal diabetes insipidus

Autosomal dominant neurohypophyseal diabetes insipidus (ADNDI) is a rare variant of idiopathic central diabetes insipidus. Several different mutations in the human vasopressin-neurophysin II (AVP-NP II) gene have been described. We studied nine family members from three generations of an ADNDI pedigree at the clinical, morphological, and molecular levels. AVP concentrations were measured during diagnostic fluid restriction tests. Coronal and sagittal high resolution T1-weighted images of the pituitary were obtained from affected and healthy family members. PCR was used to amplify the AVP-NP II precursor gene, and PCR products were directly sequenced. Under maximal osmotic stimulation, AVP serum levels were close to or below the detection limit in affected individuals. Magnetic resonance imaging studies revealed the characteristic hyperintense ("bright spot") appearance of the posterior pituitary in two healthy family members. This signal was absent in all four ADNDI patients examined. The coding sequences of AVP and its carrier protein, neurophysin II, were normal in all family members examined. Affected individuals showed a novel single base deletion (G 227) in the translation initiation codon of the AVP-NP II signal peptide on one allele. The mutation in the AVP-NP II leader sequence appears to be responsible for the disease in this kindred, possibly by interfering with protein translocation. The absence of the hyperintense posterior pituitary signal in affected individuals could reflect deficient posterior pituitary function.     

Plasma cell content of main and accessory lacrimal glands and conjunctiva

Chloroquine compounds are known to cause a retinopathy which typically begins in the central fundus giving rise to a "bull's eye" macula. Ultimately peripheral changes may become apparent. In the routine eye examination of such patients emphasis has been laid on the central area of the fundus. A case is presented where the retinopathy was not diagnosed until marked peripheral changes had occurred with peripheral pigment changes, attenuated retinal vessels, slight optic atrophy, peripheral visual field restriction and a subnormal electroretinogram. The typical "bull's eye" changes were not apparent. Routine examination of the peripheral fundus by means of ophthalmoscopy and perimetry is necessary to avoid missing any such retinopathy.     

Visibility of the nailfold plexus and heredity

The parents of 37 normal healthy teenagers selected on the basis of nailfold capillary patterns (16 low-plexus children and 21 high-plexus children) were examined by capillary microscopy and rated "blindly" for plexus visualization scores (PVS). The hypothesis that high PVS is a hereditary trait transmitted as a monogenic autosomal dominant is supported by these data. The additional hypothesis that the high PVS may be associated with a higher social class is also confirmed in this sample. The transmission of high PVS in schizophrenics, where it is frequently observed in association with more serious features of this disease, appears to follow the same mode of inheritance as in normal subjects. The importance of detecting a biological hereditary characteristic which appears to have a modifying effect on the schizophrenic process is emphasized.     

Meconium ileus equivalent in adults with cystic fibrosis of pancreas: a report of six cases

Eleven episodes of "meconium ileus equivalent" have been seen in six adults with cystic fibrosis of the pancreas. Three patients were initially treated surgically; one died and the other two developed serious postoperative chest infections. Six episodes were successfully treated medically with acetylcysteine orally and by enema, nasogastric suction, and intravenous fluids. Operation should be avoided if possible, and maintenance treatment with acetylcysteine may be necessary to prevent relapse.     

Blood lead levels in Victorian children

A recent study of lead levels in the blood of Sydney schoolchildren purported to show "an alarming situation of epidemic proportions", with up to 24% of children in one survey having blood lead levels greater than 25 microgram/100 mL (1.21 mumol/L). In the present study, 446 Victorian children were tested for lead level in venous blood, showing a mean blood lead level of 11.4 microgram/100 mL (0.55 mumol/L), and only six children (1.3%) with blood lead levels in excess of 25 microgram/100 mL (1.21 mumol/L) were found. It is suggested that the blood lead levels in the Sydney study may have been falsely high because of the use of capillary blood samples which are prone to contamination.     

Myelination in organotypic cultures of sympathetic ganglia

Explants of mouse superior cervical ganglion (SCG), co-cultured with dorsal spinal cord, were grown for up to 4 weeks in vitro. In such cultures, scattered internodes of peripheral nervous system (PNS) myelin were observed, apparently associated with SCG neurites. Although rare, the incidence of PNS myelination in this system might merit further experimentation to provide a model facilitating the evaluation of postganglionic sympathetic myelination, which in vivo may be both extensive and morphologically unusual.