D. van Velzen

The effect of intrauterine growth retardation on the development of renal nephrons

Objective To investigate the effect of Type II (asymmetrical) intrauterine growth retardation (IUGR) on renal development.

Strictures of ascending colon in cystic fibrosis and high-strength pancreatic enzymes

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.

Selective decontamination with nystatin for control of a Candida outbreak in a neonatal intensive care unit.

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.

Megacystic microcolon intestinal hypoperistalsis syndrome: Evidence of a primary myocellular defect of contractile fiber synthesis

Two infant boys with megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) are reported. Presenting with neonatal intestinal obstruction, they underwent laparotomies that showed megacystis, microcolon, and aperistaltic shortened small bowel without any mechanical obstruction. Patient 1 gradually improved and is developing normally at home, on a normal diet without genitourinary or gastrointestinal complaints (now 11 years old). Patient 2, who underwent vesicoamniotic drainage antenatally, never developed adequate gastrointestinal or genitourinary function in spite of appropriate diversion and pharmacologic support. He showed progressive deterioration and died at the age of 7 months. Detailed histo-immuno- and ultrastructural pathology assessment, although confirming results in the existing literature in some aspects, showed previously unreported neuronal dysplastic changes associated with increased laminin and fibronectin. Although patient 1 showed ultrastructural features of vacuolar degeneration of smooth muscle as reported in the literature, patient 2 showed ultrastructural and histochemical evidence of excessive smooth muscle cell glycogen storage with severely reduced contractile fibres displaced to the extreme periphery of the cells, suggesting a fundamental defect of glycogen-energy utilization. A deficiency of fiber synthesis as the alternative primary defect is discussed. In both cases, a two-step genetic defect may explain the variability in clinical outcome and pathological findings.

Stereological estimation of the absolute number of glomeruli in the kidneys of lambs.

An association between the arrest of renal development and intra-uterine growth retardation (IUGR) has been demonstrated in human beings and it has been suggested that the same defect may occur in the kidneys of lambs affected by IUGR. Using design-based stereological methods, the physical disector and Cavalieris principle, smaller absolute numbers of glomeruli were found in all six IUGR lambs studied with a low birthweight and in two of six control lambs studied with a normal birthweight than in other lambs with a normal birthweight. There was no difference in absolute numbers of glomeruli between twin births and singletons. The absolute numbers of glomeruli in three stillborn lambs were distributed among results obtained from the normal and IUGR lambs in accordance with their individual bodyweights. IUGR had a profound detrimental effect on the renal development of the lambs.

Composition of the inflammatory infiltrate in pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans): a prospective, comparative immunophenotyping study.

Dermatopathological evaluation of pediatric preputial inflammatory disease rarely allows for specific diagnosis other than pediatric penile lichen sclerosus et atrophicus (balanitis xerotica obliterans, LSA/BXO). A prospective immunopathological study was performed on 20 consecutive, unselected, clinically and histopathologically confirmed LSA/BXO cases to determine the relative presence of T and B lymphocytes. There were seven cases with early stages of disease, eight with florid disease, and five with later stages of disease. Two ritual circumcision specimens and 12 specimens with non-LSA/BXO balanitis, collected during the same period, were used as controls. The infiltrate in LSA/BXO patients was wholly composed of T cells (positive with UCLH-1 antibody) in all cases. B cells (positive with L-26 antibody) were found only focally in small, discreet, easily recognizable (follicular or early follicle-like) aggregates, positioned slightly deeper than the band-like infiltrate of T cells. T cells were inconspicuous in 9 of the 12 control specimens. In the three other controls, T cells were much more obvious and these patients showed clinical features possibly suggestive of LSA/BXO in early, prediagnosable phases of development. We conclude that limited immunophenotyping may be a useful adjunct to diagnosis in pediatric cases in which only limited tissue is available or the disease may be more difficult to classify with confidence.

Cerebral malaria in the Rhesus monkey (Macaca mulatta): observations on host pathology

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.

HIRSCHSPRUNG'S DISEASE: A Viral Etiology?

This study investigates the hypothesis that Hirschsprungs disease (HD), congenital rectal aganglionosis, may be etiologically linked to antenatal cytomegalovirus (CMV) infection. Bowel specimens from 72 HD patients, 144 control I infants (Hirschsprung-like symptoms, normal histology), and 36 control II infants (deaths from nongastrointestinal causes) were analyzed for CMV genomes by polymerase chain reaction. Positive results were obtained in 6 HD patients (8.8%) and none of the controls. Our findings suggest that antenatal CMV infection, a potentially preventable condition, may be one of the etiological factors in HD.

Collateral Blood Flow in the Distal Ileum of Neonatal Piglets: A Clue to the Pathogenesis of Necrotizing Enterocolitis

Normal blood flow was measured in two regions of the ileum (distal and proximal) of normal birth weight (NBW) and low birth weight (LBW) neonatal piglets. Compensatory collateral blood flow in response to occlusion of vessels in the mesenteric vascular arcades was also measured in distal and proximal ileum of NBW and LBW neonatal piglets. Under normal control conditions the blood flow in the distal ileum of NBW piglets is reduced (40% less than proximal) and in LBW animals this reduction is greater (55% less than proximal). Both proximal and distal ileum of NBW animals but the proximal ileum only of LBW animals could mount compensatory collateral flow, whereas the distal ileum of LBW animals was unable to do so. This decompensation in LBW distal ileum may explain the predilection of NEC lesions for the distal ileum and proximal colon.

PCNA independence of Ki‐67 expression in HPV infection.

12 Infectious Wart lesions were stained using the streptavidin‐biotin immunoperoxidase method for PCNA10, MIB‐1 (Ki‐67 equivalent antigen) and Human Papilloma Virus antigen to study the effect of HPV presence on epidermal proliferation. Using strict methods to avoid observer bias, Ki‐67 antigen was found in a high proportion of nuclei in the suprabasal layers together with HPV antigens, in the absence of PCNA staining. This finding indicates that DNA synthesis related, Ki‐67 antigen bearing structures can be raised in the human nucleus in the absence of induction of PCNA bearing structures, suggesting also structural independence between the antigen bearing molecules.