Colin L. Berry

Improving vascular grafts: the importance of mechanical and haemodynamic properties

In the last 40 years, as techniques and materials have improved, the success rate of vascular prostheses with a diameter greater than 6mm has risen steadily, 5‐year survival rates exceeding 95% in most centres. With smaller grafts no comparable improvement has occurred, the majority failing within 5 years, usually as a result of intimal hyperplasia and, ultimately atherosclerosis, in and around the downstream anastomosis. Clinical evidence suggests that the patency rates of small grafts are improved by matching the elastic properties of the graft to that of the artery into which it is placed. Although there is little reliable evidence that ‘elastic mismatch’ per se is the cause of intimal hyperplasia, it is generally accepted that mechanical factors are important in its genesis. These include disturbed flow at the anastomosis leading to fluctuations in shear stress at the endothelium (a known cause of intimal hyperplasia in normal arteries), injury due to suturing and stress concentration at the anastomosis. Few suitable materials or techniques have yet been developed to improve the long‐term survival rates of small grafts. Recent advances in tissue engineering in which prostheses are manufactured by culturing vascular smooth muscle cells on a tubular scaffold of biodegradable polymer may ultimately make it possible to manufacture biologically and haemodynamically compatible grafts with diameters as small as 1mm. Copyright

The effects of maternal protein deprivation on the fetal rat pancreas: major structural changes and their recuperation

There is evidence that low birth weight and poor growth in early life cause a long‐term predisposition to non‐insulin‐dependent diabetes. Morphological changes were assessed in fetal rat pancreas subjected to both pre‐ and post‐natal maternal protein deprivation (LP). Further groups were subjected to purely prenatal maternal protein deprivation (preLP) and purely postnatal maternal protein deprivation (postLP), as well as a control group. The results show that the LP and postLP groups had fewer but larger islets than the control group, while the preLP group had more numerous, smaller islets. All three low protein groups had more irregularly shaped islets than the control group. There was a reduction in the amount of beta cells within each islet in all three protein‐deprived groups. The LP and postLP groups showed a reduction in the percentage of islet tissue and beta cells per pancreas, but the percentage of islet tissue expressed per unit body weight was similar in all four groups. These results show that in maternal protein deprivation, homeostatic mechanisms ensure a constant amount of pancreatic endocrine tissue per unit of body weight. However, there remain major structural changes in the size, shape, and composition of the islets. These results support the theory that early development profoundly affects the structure of the pancreas and may play a role in the later development of adult diseases, such as non‐insulin‐dependent diabetes mellitus.

Intravascular Papillary Endothelial Hyperplasia in the skin and subcutaneous tissue

Twenty-four cases of Intravascular Papillary Endothelial Hyperplasia (IPEH) have been studied. IPEH comprises approximately 2% of benign and malignant vascular tumours of the skin and subcutaneous tissue. This peculiar tumour-like process lacks specific clinical characteristics and its diagnosis must be based on microscopic examination. Histologically it is characterised by a papillary proliferation of endothelial cells forming vascular channels, commonly assocaited with thrombus and in some cases simulating angiosarcoma. — Follow-up of 10 cases indicates a benign clinical course.

Argyrophilic and hormone immunoreactive cells in normal and hyperplastic pancreatic ducts and exocrine pancreatic carcinoma

Scattered argyrophil cells were present in normal, large, medium-sized and small pancreatic ducts (ductules). There was marked increase in argyrophil cells in ducts with hyperplastic epithelium. Argyrophil cells were also found in 67.7% of all exocrine pancreatic carcinomas. In a well differentiated group including cystadenocarcinoma, mucinous carcinoma and well differentiated ductal adenocarcinoma argyrophil cells were found in all cases examined. Using four antisera (against insulin, glucagon, somatostatin and gastrin), insulin, glucagon and somatostatin cells were identified in 2.65%, 0.001% and 1.2% of normal ducts, and 7.5%, 2.4% and 4.6% of ducts with hyperplastic epithelium respectively and were also greatly increased in numbers in the latter group. Immunoreactive cells were present in 66.7% of exocrine carcinomas. Cells reactive for insulin were found in 7/15 cases; glucagon in 6/15 cases; somatostatin in 5/15 cases and gastrin in 2/15 cases. Eight cases contained two or more than two types of immunoreactive cells. The presence of argyrophil and hormone immunoreactive cells in pancreatic ducts and carcinomas is indicative of the close developmental relationship between endocrine and exocrine parts of the pancreas. The inter-relationship of response in the different cell types following stimulus suggests that injury to a common precursor may be involved.

Effects of hypertension on the intercellular contacts between smooth muscle cells in the rat thoracic aorta.

A qualitative and quantitative study was made of the contacts between muscle cells in the media of the thoracic aorta of hypertensive and normotensive Sprague-Dawley rats. In ultrathin sections, the type and number of contacts per 100 microns cell perimeter and per 100 cell profiles were determined using an image analysis computer. The intercellular contacts in both groups were in the form of simple appositions, interdigitations, intermediate junctions and nexus junctions. In the hypertensive group, there was a reduction in the number of simple appositions and intermediate junctions, but the nexus junctions (which provide intercellular communication) were increased in density. Interdigitations demonstrated no change. Decreased intercellular cohesion may play an important role in the mechanisms by which hypertension predisposes degeneration of the media with progression to ectasia, aneurysm formation and dissection.

Nexus junctions between vascular smooth muscle cells in the media of the thoracic aorta in normal and hypertensive rats. A freeze-fracture study.

Freeze-fracture electron microscopy and image analysis have been used to study the nexus junctions (NJ) between smooth muscle cells in the media of the thoracic aorta of normal and hypertensive Sprague-Dawley rats. The NJ found in both groups revealed particles on the P-face and depressions or pits in the E-face. Within each face, particle- or pit-free areas were identified in some junctions. NJ are usually surrounded by a narrow area devoid of particles and in certain fracture planes a close relationship of NJ with smooth endoplasmic reticulum was seen. Larger and more irregular NJ were found in the hypertensive group than in the controls. The differences observed in the hypertensive animals may be associated with an increase in tangential tension in the vessel wall.

Is the incidence of primary adenocarcinoma of the lung increasing

Primary carcinoma of the bronchus is a major cause of death in males and females. Several studies report an increase in the incidence of adenocarcinoma and have suggested that this reflects changes in smoking habits or, alternatively, that it is a spurious rise due to changes in diagnostic criteria. To examine the latter suggestion we reviewed three cohorts of bronchial carcinoma from 1970, 1980 and 1990, using immunocytochemical techniques to refine diagnosis. We found that squamous cell carcinoma had been consistently overdiagnosed and adenocarcinoma and adenosquamous carcinoma consistently underdiagnosed in all groups. Also, many tumours showed evidence of divergent differentiation with both squamous and glandular components present. There was a small, but real temporal increase in the proportion of adenocarcinoma over the 10 years between 1970 and 1980, but this was not sustained between 1980 and 1990.

Purkinje cell toxicity ofβ-aminopropionitrile in the rat

Compounds causing neurolathyrism are putative aetiological agents in neurodegenerative disorders including amyotrophic lateral sclerosis.β-Aminopropionitrile (BAPN) is one such compound. We have administered this lathyrogenic agent at a dose of 1 g/kg by the intraperitoneal route in experiments in adult Sprague-Dawley rats during a period of 10 weeks. The rats developed marked kyphoscoliosis, ataxia with paralysis and muscle wasting of the hind limbs. Vacuolation and loss of Purkinje cells developed, but no anterior horn cell degeneration was noted. Immunohistochemical studies of phosphorylated neurofilaments and the 72 kDa heat shock protein were normal and no intraneuronal ubiquitinated inclusions were seen. High-dose intraperitoneal BAPN in the rat causes Purkinje cell changes, but no other central nervous system abnormalities.

Development and pathology: the Pax gene.

During development, many genes support different functions at different times, when they are expressed in different tissues, or in response to different transcription factors. Pathologists should be cautious about ascribing functions to such genes in pathological processes. Copyright

Retinoic acid, neoplasia, differentiation and development

Retinoic acid has pronounced effects on cultures of neoplastic cells. These have attracted the attention of pathologists, but it is important to note that much of the critical data about retinoic acid has been obtained from the current extension of our knowledge in the field of development. Some of these changes are reviewed here.