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Organ development may be assessed by estimating the total number of functional units within an organ over time; the potential functional capacity of that organ may be represented by the total number of functional units present in the fully developed, mature organ. Relative development of the lung at birth is essential to provide sufficient oxygenation of body tissues and so maintain ex utero life. Estimation of the number of one type of functional unit of the lung – terminal bronchiolar duct endings – provides important information regarding development of the lung. This investigation used stereological techniques, specifically Cavalieri’s Principle and the “physical disector”, to estimate total number of terminal bronchiolar duct endings in the upper lobe of the right lung of a group of 14 control infants between 0 and 66 weeks post-natal age. Results demonstrate that total terminal bronchiolar duct ending number does not increase significantly over the first 24 weeks of post-natal life in normal infants ( P =0.997). The unbiased, design-based techniques used in this paper confirm previous model-based research that indicates that terminal bronchiolar duct ending development is completed before birth.

Objective: To determine the precise contribution of congenital malformations to perinatal mortality in a region. Design : Prospective, descriptive. Setting : Region, Delft–Westland–Oostland (DWO) in the Netherlands. Material and methods : The registration was based on data concerning all deliveries of women domiciled in the health region DWO of the Netherlands. The incidence and contribution of congenital malformations to perinatal death was evaluated by a team consisting of a gynaecologist, a paediatrician and a paediatric pathologist. Malformations were classified as lethal or nonlethal and recorded separately for stillbirth (from 28 weeks gestation) and liveborn infants with 7-day follow-up. Results : In 10 years (1993–1992) 28 983 children were born in the region DWO. The perinatal mortality was calculated as 247 cases (0.85%). The overall incidence of congenital malformations in the perinatal death-group was 33%. Lethal congenital malformations were found in 51% of the cases in the stillbirth-group and 70% of the cases in the neonatal death-group. Congenital malformations of the central nervous system are mostly lethal in the stillbirth-group (45%). Cardiovascular- and pulmonary-defects were more prominent in the neonatal period (27% and 33% respectively of the neonatal deaths). Uro–genital and minor malformations (miscellaneous) are more often seen in perinatal deaths without being a contributor to the cause of death. Conclusions : As most congenital malformations are multifactorial in origin, it is in the understanding and control of such conditions that efforts and resources should now be turned. Through a detailed postmortem fetal and placental examination and clinical–pathological correlations lethal congenital malformations were found in 51% in stillbirths (mainly central nervous system) and 70% in neonates (mainly cardiovascular and pulmonary defects).

The oxidation of aqueous solutions of Fe(II)NTA was investigated in a bubble column reactor. The rate of the oxidation reaction was found to be proportional to the partial pressure of oxygen and to have an order of 0.5 with respect to the Fe(II)NTA concentration. The overall transfer of oxygen appears to be predominantly reaction controlled for Fe(II)NTA concentrations in the order of 1 mmol 1−1 whereas for high concentrations (100 mmol 1−1) mass transfer becomes the controlling factor. Overall mass transfer coefficients and reaction rate constants were determined in the range between 25 and 60 °C and for a wide range of Fe(II)NTA concentrations (5–250 mmol 1−1).

Previous in vitro studies have suggested that successful neural crest cell migration in the developing gut could be influenced by the composition of the extracellular matrix components, tenascin and fibronectin. The authors aimed to gain insight into the pathogenesis of Hirschsprung's disease (HD) by studying the distribution of tenascin and fibronectin in bowel specimens of patients with HD. Immunohistochemical examination was performed in specimens from 10 HD patients (8 aganglionic, 5 transitional, and 10 normoganglionic zones) and 18 age- and site-matched controls undergoing other types of gastrointestinal surgery. The distribution of tenascin was restricted to the basement membranes of the smooth muscle and vasculature, and in the basement membranes surrounding neuronal ganglia in all the controls and in 10 proximal normoganglionic HD specimens. More intense tenascin immunofluorescence was observed in the smooth muscle basement membranes of the muscularis externa of eight aganglionic and five transitional zones of HD. Wide-spread distribution of fibronectin was found in all the basement membranes as well as in the lamina propria and submucosa of all control and 10 normoganglionic HD sections. However, more intense immunofluorescence with fibronectin was observed in all the layers of eight aganglionic and five transitional zones of HD specimens. The present findings show that the mesenchymal and basement membrane extracellular matrix constitution is abnormal in the affected bowel of HD. Although a causal relationship has not been demonstrated, corroborative evidence from earlier animal experiments in other studies suggests that the extracellular matrix abnormalities may contribute to the pathogenesis of HD.

Summary A rat-specific mouse monoclonal antibody, exclusively reacting with a blood-brain and blood-nerve barrier protein, was employed to assess the post-natal, age-related changes in morphology and intraparenchymal distribution of barrier competent microvessels in normal rat forebrain. Antibody binding first appeared in single cells over the external surfaces of the brain between days 3 and 6 post-partum and increased progressively with age. In mature rats, the cerebral grey matter showed higher vascularization by barrier competent microvessels than white matter. Microvessels in the hippocampus were immunocytochemically more avid but less “networked” than the rest of the neocortex. These features may be related to morphological, metabolic and haemodynamic changes associated with brain growth and development.

Selective decontamination of the digestive tract (SDD) with oral nystatin was evaluated as a measure to control an outbreak of Candida infection in a neonatal intensive care unit (NICU). Seventy-six out of 106 neonates who carried Candida spp. received the main study manoeuvre (the application of oral nystatin in the throat and stomach) during the 12-month open trial. One third of the neonates weighed < 1500 g whilst about half were being ventilated. The mean stay was 33.2 d (SD +/- 46.9). Two cases with candidaemia within a fortnight were associated with a yeast carriage rate in the NICU of about 50%; more than 80% of the isolates were Candida parapsilosis. During the implementation period there were four new neonates with fungaemia caused by C. parapsilosis. Once the carriage rate dropped below 5% (P < 0.001), no new cases of systemic infection with the outbreak strain were recognized in the following 8 months. It took 3.5 months to control the outbreak. The observation that all other clinical diagnostic samples were free from Candida suggests that translocation from throat or gut into the systemic circulation occurred. SDD with oral nystatin was effective in reducing the yeast carriage index (mean index 1.93, before SDD; 0.45, after SDD; P < 0.001). A significant reduction of carriage, both in rates and indices, is thought to have contributed to the control of this candida outbreak.

Infection was induced in five rhesus monkeys (Macaca mulatta) by intravenous inoculation with a virulent strain of Plasmodium knowlesi. Approximately one week after inoculation, four of the exposed animals developed acute malaria and died or were killed when moribund after varying periods of illness. Post-mortem and light microscopical examination showed marked cerebral vascular congestion and widespread plugging of the brain capillaries and venules (microvessels) by heavily parasitized erythrocytes mixed with uninfected erythrocytes. Electronmicroscopically, the major changes seen were adherence of large numbers of parasitized erythrocytes and macrophages to swollen microvascular endothelial cells; increased numbers of fibroblasts and deposition of collagen bundles in the extracellular matrix around damaged and parasite-packed microvessels were also found in many areas. This animal model may prove useful for further investigation of the pathogenesis of cerebral malaria.

Valid alternatives to the selective catalytic reduction (SCR) process for the removal of nitrogen oxides from waste gases (denoxing) may be found in wet scrubbing processes where the low solubility of NO in aqueous media is enhanced by the application of chelate complexes. The most widely used complex for this purpose is Fe II EDTA (iron II ethylenediaminetetra-acetic acid). Iron II nitrilotriacetic acid (Fe II NTA) might be another candidate, with similar chemical properties as Fe II EDTA but available industrially at a considerably lower price. For the development of technical processes, a knowledge of the equilibrium data over a range of temperature is of prime importance. Therefore experimental investigations were carried out concerning the chemical equilibrium of the reaction:NO + Fe II NTA ⇌ Fe II NTA · NO The equilibrium constant was determined in the temperature range 22–80 °C. All experimental data fit the equilibrium constant equation well: K p = 3.05 x 10 -8 exp(7332/T) (bar -1 ) The equilibrium constant for Fe II NTA is approximately 25% lower than the constant for Fe II EDTA. However, considering the price difference between the two complexants, Fe II NTA is an interesting alternative to Fe II EDTA.

Previous immunohistochemical studies have shown an abnormal distribution of extracellular matrix (ECM) proteins, including laminin, in the smooth muscle layer of muscularis externa in Hirschsprung's disease (HD) bowel. These findings supported the hypothesis that an abnormal ECM microenvironment may be responsible for the failure of migration and/or development of the neural crest cells in the gut in HD. In order to determine the cause of the abnormality in laminin distribution, solid-phase enzyme-linked immunosorbent assays and immunoblots were used to quantitate the ECM protein laminin and characterize its subunits, respectively, in extracts of the dissected smooth muscle layer of the muscularis externa. In the aganglionic bowel, laminin (median concentration, 32.4 ng/mg of tissue) was found to be present in significantly greater quantity than in both the normoganglionic bowel of the same specimen (median, 17.2 ng/mg, P less than or equal to .05) and the normal bowel of age-matched controls (median, 9.7 ng/mg, P less than or equal to .05). Laminin concentration was also found to be significantly higher in normoganglionic HD bowel (median, 17.2 ng/mg) than in age-matched control specimens (median, 10.8 ng/mg, P less than or equal to .05). No difference was observed in the subunit composition of laminin in HD and control extracts analysed by immunoblot after polyacrylamide gel electrophoresis. This study demonstrates a quantitative abnormality of laminin in the bowel in HD, supporting the hypothesis that "abnormal microenvironment" may have a role in the pathogenesis of HD.

In vitro neurite outgrowth and neuronal survival are promoted by laminin, and neuronal migration is promoted by collagen type IV. This led to the hypothesis that Hirschsprung's disease (HD) could be the result of an abnormal extracellular matrix microenvironment in the affected bowel during embryogenesis. Using indirect immunohistochemistry, we studied the distribution of laminin and collagen type IV in the bowel specimens of eight HD patients (four neonates and four infants) and 16 age- and site-matched controls from non-HD patients. In eight HD specimens, the tissue studied was from the aganglionic, transitional, and proximal normoganglionic zones. Uniform distribution of laminin and collagen type IV was observed in the basement membranes of all control specimens. The semiquantitative abnormality in the distribution of these proteins in HD occurred as follows: immunoreactivities were more intense in the inner circular layer, diminishing with a gradient in the outer muscularis externa in six of six aganglionic, four of five transitional, and three of eight normoganglionic sections. The qualitative abnormality of these proteins in HD was speckled immunofluorescence outside the basement membranes of the muscularis externa in all three zones of neonatal specimens only. These findings support the microenvironment hypothesis of the pathogenesis of HD.

The ossification of the anterior skull base, especially the lamina cribrosa, has been studied by computed tomography and histopathology. Sixteen human fetuses, (referred to our laboratory for pathological examination after spontaneous abortion between 18 and 32 weeks of gestation) and three infants, (1, 2 and 6 years of age, respectively) were examined. The cartilaginous preformation of the anterior skull base creates a 'pseudo-defect' on CT in the coronal plane, even with ultra thin sections and high resolution CT. By the age of 6 years of life this 'artefact' is no longer, as the present ossification of the lamina cribrosa is, by that time, complete.

We describe the radiological and histopathological findings in five children with cystic fibrosis who presented recently to our hospital. Each child underwent surgery after failing to respond to medical management for suspected distal intestinal obstruction syndrome. Four patients had preoperative ultrasound and contrast enema examinations. Wall thickening and dilatation of the ascending colon was seen on ultrasound and contrast enema revealed a stricture of the ascending colon in all four. At surgery these findings were confirmed. All five patients had histopathological changes of post-ischaemic ulceration repair. One child had symptoms of intestinal obstruction 5 months after right hemicolectomy. Radiological investigation revealed a stricture in the descending colon which was resected. The histopathological changes were the same as before. Colonic strictures should be considered in cystic fibrosis patients who do not respond to medical management of distal intestinal obstruction syndrome.

We have observed five children with cystic fibrosis, who presented over 2 months, with meconium ileus equivalent that failed to respond to medical management. At surgery, four had a stricture in the ascending colon, and all had histopathological changes of post-ischaemic ulceration repair, with mucosal and submucosal fibrosis. The only common change in the management of these children was a switch from conventional enteric-coated pancreatic enzymes to high-strength products 12-15 months before presentation.

Cycles for the thermochemical decomposition of water belonging to the FeCl family have been considered potentially attractive. An analysis of the thermal efficiency, investments costs and development potential of this family is presented, where electrolysis of water serves as a reference process. It is concluded that the thermal efficiency of these cycles is probably considerably below the values obtained with direct electrolysis whereas investment costs are presumably higher by a factor of more than two. Main problem areas are situated in the hydrolysis of FeCl2 as well as in the thermal decomposition of FeCl3. Both problems have to be solved simultaneously; finding a solution to only one will not be sufficient to build an attractive process. A number of possible alternative solutions to these problems are discussed.

Preclinical studies were performed in mice, rats and dogs of cis-diamminedichloroplatinum(II) (CDDP) and its derivatives cis-1,1-di(aminomethyl) cyclohexane platinum(II) sulphate (TNO-6), cis-diammine-1,1-cyclobutanedicarboxylate platinum(II) (CBDCA) and cis-dichloro, trans-dihydroxybis-isopropylamine platinum(IV) (CHIP). In mice toxicity and antitumour activity were determined. All three derivatives were at least as toxic as CDDP for haemopoietic stem cells and were less active than CDDP against the mouse tumours leukaemia L1210 and osteosarcoma C22LR. Toxicology studies in rats revealed no renal toxicity after a single dose of TNO-6. Fractionated doses of TNO-6 and CBDCA did cause renal toxicity but less than CDDP. CHIP produced little or no kidney damage. In dogs, TNO-6 (1.5 mg/kg) produced more severe kidney damage--although this was reversible--than CDDP (2 mg/kg). Half-lives of distribution were 4.0-5.1 min for TNO-6 and 9.7 min for CDDP, while half-lives of elimination were 3.6-6.6 days and 5.9 days respectively. Plasma levels, normalized for the dose, were at least two times higher after TNO-6 than after CDDP. Twelve weeks after drug administration, plasma levels were undetectable, while tissue concentrations could still be measured. The platinum concentration in kidney cortex was higher after CDDP than after TNO-6.

The reaction of SO 2 , Br 2 and H 2 O, forming HBr and H 2 SO 4 , is one of the reactions of the hybrid cycle for thermochemical decomposition of water, Mark-13. Experimental work on this reaction is described in this paper. Equilibrium measurements show that high sulfuric acid concentrations (higher than 80 wt%) are attainable. At low sulfuric acid concentrations only traces of Br 2 and/or SO 2 remain in the gaseous phase. Besides the equilibrium determinations, development work by dynamic experiments has also been carried out. A simple mathematical model for the reaction rate in packed columns has been developed which satisfactorily fits the available experimental data.

The experimental work in the field of the development of cycles of the Fe/Cl family is described. It appeared that application of a homogeneous support material for the gas-solids reaction was not feasible due to unexpected side reactions. The hydrolysis of ferrous chloride has been found to give good results and the development and operation of a continuously operating bench-scale reactor for this reaction has been described. The chlorination of the resulting magnetite could not be performed according to the originally proposed scheme. A satisfactory alternative has been found, i.e. chlorination at 150–200C with only hydrogen chloride and introduction of the reverse Deacon reaction as a fourth reaction in the cycle.

The Mark-13 cycle, invented by Schutz and Fiebelmann in 1974, consists of the following three reactions: SO 2 + Br 2 +2 H 2 O → H 2 SO 4 +2 HBr , (320–370 K) 2 HBr → H 2 + Br 2 , (electrochemical) H 2 SO 4 → H 2 O + SO 2 +0.50 2 . (1000–1100 K) In the present paper the state of the art of the experimental development work carried out at JRC-Ispra is given. The results obtained have been considered a sound basis for the design and construction of a complete laboratory-scale cycle. The expected net hydrogen production rate of this plant is 4.0 gmol/h, i.e. about 100 l/h S.T.P. The aim of the work is the construction of a reliable small scale model of the process which should yield indispensable information for further scale-up. Therefore we applied design and/or simulation rules in the design calculations for the process. It is believed that this installation is the first demonstration of a complete thermochemical hydrogen production process.

The bench-scale plant for thermochemical hydrogen production by the Mark-13 process has been successfully operated since May 1978. The nominal hydrogen production rate of the plant working at atmospheric pressure is 100 STP 1. h −1 . A concise description of the process flow scheme is given. Operation of the plant demonstrated that thermochemical water decomposition is a viable process and a valid alternative to other processes for hydrogen production from water. The availability of the plant for experimental work was very high and no special start-up procedure was required. All reactions and product separation units were working within their specifications and no by-product formation was observed.