Nineteenth century mortality at the Royal Hospital for Sick Children, Glasgow.

BACKGROUND AND AIMS: Since Glasgow's Royal Hospital for Sick Children opened in 1882, significant advances have been made in child health. Our aim was to investigate the hospital mortality that occurred in the last decade of the 19th century at Royal Hospital for Sick Children. METHODS AND RESULTS: Hospital mortality records for the decades, 1890-1899, were collected from the Archives of the Royal Hospital for Sick Children. Data were extracted from the hospital inpatient records and the pathology records. In the decade 1890-1899, there were 731 hospital deaths. The main cause of death at that time in the 19th Century was infection, particularly of the respiratory tract. The age at which death occurred was analysed and the recorded cause were analysed as was the distance patients travelled to the hospital. The ratio of boys to girls and length of inpatient stay was similar to that seen in the hospital currently. CONCLUSION: This study records the mortality in a children's hospital in a large developing industrial city in the 19th century as experienced in a children's hospital.

Brain peptides and glial growth. II. Identification of cells that secrete glia-promoting factors.

Glia-promoting factors (GPFs) are brain peptides which stimulate growth of specific macroglial populations in vitro. To identify the cellular sources of GPFs, we examined enriched brain cell cultures and cell lines derived from the nervous system for the production of growth factors. Ameboid microglia secreted astroglia-stimulating peptides, while growing neurons were the best source of the oligodendroglia-stimulating factors. These secretion products co-purified by gel filtration, anion exchange chromatography, and reverse-phase high performance liquid chromatography with GPFs isolated from goldfish and rat brain. Our findings suggest that glial growth in the central nervous system is regulated in part by a signaled release of peptides from specific secretory cells.

Pericarditis resulting from infection and fistula between the left ventricle and transverse colon.

A patient is described who presented with acute pericarditis and acute ulcerative colitis. Previous resection of a left ventricular apical aneurysm had been performed four years earlier, and no problems had arisen until pericarditis developed. After hospital admission and investigation, the patient's condition suddenly deteriorated, and he died. Autopsy showed the causes of death to be a fistula between the left ventricle and transverse colon and septicemia.

Cefotaxime lavage in children undergoing appendicectomy.

In an attempt to reduce postoperative sepsis, a series of randomised, double-blind studies was begun in 1982, using cefotaxime as backbone therapy. Up to 1985 (stages I and II), the best results were obtained using a combination of cefotaxime (75 mg/kg intravenously in 3 doses at 12-hourly intervals) plus metronidazole (10 mg/kg intravenously in 3 doses), both drugs administered 1 hour before surgery (preoperatively) or at anaesthetic induction (peroperatively). In 300 consecutive cases, the wound infection rates were 1% in uncomplicated acute appendicitis and 5% in perforated/gangrenous appendices. The present study (stage III) reports the findings in 401 consecutive patients: 215 treated with the above regimen, either pre- or perioperatively (group 1) and 186 who additionally had peritoneal lavage with cefotaxime 2 g/L during surgery (group 2). There were 16 wound infections overall, 2 among patients administered prophylaxis preoperatively and 14 in those administered prophylaxis perioperatively. All produced mixed cultures, with Escherichia coli, Streptococcus milleri and Bacteroides fragilis predominating. The overall figures for postoperative sepsis are 12/215 (5.6%) in the non-lavage group and 8/186 (4.3%) in the lavage group. Among patients with a perforated and/or gangrenous appendix, the wound infection rate was 8/72 (11.1%) in the non-lavage group (group 1) and 4/66 (6.1%) in the lavage group (group 2). Each group had 2 cases of pelvic abscess.

Additional Plasmodium species from Anolis lizards of Hispaniola and Panama.

Saurian malaria parasites in the Caribbean were previously represented by only two species, Plasmodium azurophilum and P. floridense. An additional three species of Plasmodium occur on Hispaniola which appear, because of morphometric and qualitative similarities, to be related to South and Middle American species: a subspecies of Plasmodium tropiduri in Anolis cybotes; a population of Plasmodium minasense anolisi in A. cybotes and A. distichus; and another parasite in A. distichus which is designated as a subspecies of a previously undescribed Plasmodium species in Anolis limifrons. Taxonomic descriptions based upon morphology of mature schizonts and gametocytes are given, the previously unknown parasites are described as new species/subspecies, and comparison is made with P. floridense which also occurs in their respective host species. A Fallisia species was also present but is not described. The increased diversity of Plasmodium parasites in Hispaniolan anoles is attributed to colonization of the island by four separate evolutionary lines of Anolis lizards, in comparison to fewer invasions of Jamaica and Puerto Rico, where only P. floridense and P. azurophilum are found.

Transovarial transmission of Rio Grande virus (Bunyaviridae: Phlebovirus) by the sand fly, Lutzomyia anthophora.

The growth of Rio Grande (RG) virus, the only phlebovirus known to occur in the United States, was studied in Lutzomyia anthophora, its suspected sand fly vector. RG viral titers in infected flies increased more than 10,000-fold within 7 days after intrathoracic inoculation. Experimentally infected female L. anthophora transmitted virus transovarially (vertically) to 54.8% of their F1 progeny. This is the first virologically confirmed demonstration of transovarial transmission of a phlebovirus by sand flies. It indicates one mechanism by which RG and possibly other phleboviruses may be maintained in nature.

Possible determination of the vector and reservoir of leishmaniasis in the Dominican Republic.

Two species of sand flies were collected by various methods from sites in the Dominican Republic. Lutzomyia cayennensis hispaniolae was the more common of the two. It was found in wooded habitats from sea level to an elevation of 442 m. This species was observed feeding on lizards (Anolis sp.) in the wild. In the laboratory, it fed only on lizards and only under lighted conditions. The other species, Lu. christophei was only found in the vicinity of seven leishmaniasis case sites. It readily fed on or probed rodents and humans. Although no naturally infected sand flies were collected, in the laboratory Lu. christophei was readily capable of transmitting the Dominican Leishmania parasite to uninfected BALB/c mice. We collected 167 specimens of three species of rodents and three Herpestes auropunctatus (mongoose) from the vicinity of two case sites. All four species are non-endemics introduced in post-Columbian times. Although we were unable to isolate parasites from any of these specimens, four of 44 Rattus rattus from one case site were seropositive for antibodies against Leishmania by indirect fluorescent antibody testing. This represents the first report of transmission of the Dominican Leishmania parasite by a sympatric species of sand fly and suggests that commensal rodents may play a role in the epidemiologic cycle.

Biology of Arboledas virus, a new phlebotomus fever serogroup virus (Bunyaviridae: Phlebovirus) isolated from sand flies in Colombia.

Six isolates of a new phlebotomus fever serogroup virus, designated Arboledas virus, were obtained from sand flies (Lutzomyia spp.) collected in northeastern Colombia. One of the isolates was made from a pool of male sand flies. By immunofluorescence, Arboledas virus is related to Caimito and Pacui viruses; by neutralization test, it is distinct. Arboledas virus neutralizing antibodies were found in the sera of opossums (Didelphis marsupialis) and humans living in the study area. D. marsupialis inoculated with the virus developed a viremia of four days' duration, and sand flies (Lutzomyia gomezi) feeding on a viremic opossum were readily infected. Transovarial transmission of Arboledas virus was also demonstrated in experimentally infected Lu. gomezi. Results of the above laboratory studies suggest that Arboledas virus is maintained in nature by two mechanisms: vertical (transovarial) transmission in the insect vector, and an alternating marsupial-sand fly cycle. The implications of this complex maintenance cycle for other phleboviruses are discussed.

Characterization of Leishmania colombiensis sp. n (Kinetoplastida: Trypanosomatidae), a new parasite infecting humans, animals, and phlebotomine sand flies in Colombia and Panama.

Characterization of Leishmania colombiensis sp.n. is presented, which on the basis of biological and molecular criteria, appears to be a new member of the L. braziliensis complex. A total of nine isolates of the new parasite were made in Colombia and Panama between 1980 and 1986: two from human cases of cutaneous leishmaniasis, six from phlebotomine sand flies, and one from a sloth. Although most closely related to L. lainsoni, L. colombiensis sp.n. is clearly distinguishable from other members of the genus by its reactivity with monoclonal antibodies, isoenzyme electrophoresis, and restriction endonuclease fragment patterns of kinetoplast DNA (k-DNA).

Epidemiology of visceral leishmaniasis in Colombia.

Epidemiologic studies were conducted during the period 1986-1988 in a small rural community in Colombia (El Callejon) where visceral leishmaniasis is highly endemic. In this community of 185 people, 14 cases of infantile visceral leishmaniasis were diagnosed in the 9 years 1981-1988. Leishmanin skin testing of a sample of the human residents showed that prevalence of Leishmania chagasi infection increased with age; overall, 51.2% of the subjects had a positive reaction. A canine surveillance program was instituted, using introduced sentinel dogs as well as the indigenous dog population. Eleven of 16 sentinel dogs were infected within 8 months of exposure; mean seroconversion time was 4.4 months. Eleven of 25 seronegative local dogs were also infected during the 26 month period; mean seroconversion time was 8 months. Parasites identified by isozyme electrophoresis as L. chagasi were recovered from 18 of 22 seropositive dogs. Collections of wild animals using baited live traps yielded mainly the neotropical opossum, Didelphis marsupialis. Leishmania chagasi was recovered from 12 of 37 (32.4%) opossums. Six of 681 female Lutzomyia longipalpis collected in the community had flagellates in their guts; cultures from 4 were identified as L. chagasi. These data confirmed that active parasite transmission occurred. The relatively high prevalence of L. chagasi infection found among D. marsupialis captured near human dwellings suggests that these animals may be an important peridomestic reservoir.

Characterization of five new phleboviruses recently isolated from sand flies in tropical America.

Five new phlebotomus fever virus serotypes (Bunyaviridae: Phlebovirus) are described. These viruses, designated Ambe, Ixcanal, Mariquita, Armero, and Durania, were isolated from sand flies (Diptera: Psychodidae) collected in Brazil, Colombia, and Guatemala. Two of the agents were recovered from pools of male sand flies. The new viruses are antigenically related to other members of the phlebotomus fever serogroup by immunofluorescence, but are distinct from the other 39 members of this serogroup by plaque reduction neutralization test.

Natural infection of humans, animals, and phlebotomine sand flies with the Alagoas serotype of vesicular stomatitis virus in Colombia.

Five isolations of the Alagoas serotype of vesicular stomatitis virus (Rhabdoviridae: Vesiculovirus) were made from naturally infected phlebotomine sand flies (Lutzomyia spp.) collected in Colombia. These are the first isolations of Alagoas virus from an arthropod. Replication of the virus occurred in laboratory-reared sand flies (Lutzomyia longipalpis) after inoculation. Bite and transovarial transmission of the virus was also demonstrated in experimentally infected sand flies. Alagoas virus neutralizing antibodies were found in sera of humans and animals living near the insect collection site; antibody rates among human residents of two nearby towns were 63% and 83%, respectively. Results of comparative serologic studies demonstrated that Alagoas virus is closely related antigenically to Indiana, Cocal, and Maraba viruses and that these four agents form a complex within the vesicular stomatitis virus serogroup. The antigenic similarity among these four viruses makes their differentiation difficult; it also raises doubts about the accuracy of current laboratory methods used for identifying isolates in this serogroup. A discussion follows on the significance of human antibodies to these agents and on the role of sand flies in their ecology.

The partially diabetic pancreas: a histological study of a new animal model.

An animal model in which part of the pancreas was made diabetic due to almost total loss of insulin-secreting B cells, while the remainder of the gland remained normal, is described. In rabbits, a vascular clamp was placed across the junction of the body and tail of the pancreas, thus occluding the circulation to the tail. Alloxan (200 mg/kg) was injected i.v., and 4 min later dextrose (0.5 g/kg) was given by the same route. After a further 2 min the clamp was removed. Thirty-four animals were studied, 17 of which died in the first postoperative week of surgical complications or of alloxan-induced toxicity to the liver and kidneys. The survivors were killed between 4 and 12 weeks after surgery and were not metabolically diabetic. They had a virtually complete absence of B cells but a normal population of A, D, and PP cells in the head and body of the pancreas. The islets in the tail of the pancreas appeared entirely normal. This model appears suitable for studying the effects of locally produced insulin on pancreatic exocrine function in metabolically normal animals.

Trypanosome transmission by Corethrella wirthi (Diptera: Chaoboridae) to the green treefrog, Hyla cinerea (Anura: Hylidae).

Seventy-two percent of 215 male green tree frog, Hyla cinerea (Schneider), captured in Alachua and Levy counties, FL, between April and mid-September 1978 and 1979 were infected with an undescribed Trypanosoma sp. None of the 31 female frogs captured concurrently was infected. Periodic sampling of the peripheral blood from the infected male frogs showed that the trypanosomes were present in high numbers only at night. Conspecific trypanosomes also were found in the mid and hind guts of female Corethrella wirthi Stone flies collected on or near male frogs in the field. Transmission of the parasite to uninfected frogs was demonstrated by exposure of male and female frogs to naturally infected flies and to parasites injected subdermally. This is the first report of parasite transmission by a species of Corethrella.

Genetic relationships among phlebotomine sand flies (Diptera: Psychodidae) in the verrucarum species group.

Isozyme data were used to identify populations of certain Lutzomyia taxa in the verrucarum species group, mostly in the series townsendi. Lutzomyia youngi Feliciangelis and Murillo and L. spinicrassa Morales, Osorno, Osorno, and Hoyos each have diagnostic allomorphs for phosphogluconate dehydrogenase (6PGDH) and fumarate hydratase (FUM). The 6PGDH and FUM data and those from 6-phospho-fructokinase and phosphoglucomutase distinguish Lutzomyia sp., a new species from Columbia to be described and named later. Data from these enzymes and glucose phosphate isomerase will separate L. townsendi (Ortiz) from the others and from L. longiflocosa Osorno, Morales, Osorno, and Hoyos, L. quasitownsendi Morales, Osorno, Osorno, and Hoyos, and L. sauroida Osorno, Morales, and Osorno (three species that are inseparable using enzyme data). Three other species, L. serrana (Damasceno and Arouck) (series serrana) and L. columbiana (Ristorcelli and Van Ty) and L. andina Osorno, Osorno, and Morales (both in series verrucarum), are morphologically distinct using conventional characters and have fixed diagnostic differences at several enzyme loci. Statistical analyses of the enzyme data using genetic identities (I), differences (D), and the amount of genetic variation among these taxa indicated that such statistics can be as useful in the study of sand fly phylogeny and population genetics as they have been for other organisms. I and D values indicated that L. longiflocosa, L. quasitownsendi, and L. sauroida are very similar (I = 0.991 and D = 0.010) and possibly are populations of the same conspecific species. The levels of divergence, based on combined enzyme data for up to 21 gene loci among the taxa, are discussed, and a dendrogram based on genetic distance is presented. The genetic data confirmed established phylogenetic relationships among the sand fly taxa based on structural similarities.

Thoracic neuroblastoma/ganglioneuroma.

The Executive Committee of the B.A.P.S. instituted a collaborative study of patients with thoracic neuroblastoma treated by members in the British Isles. The study covers patients diagnosed in the decade 1970-1979. There is clear evidence of thoracic disease in all patients reported but there is a problem in defining whether the thoracic disease is primary or part of disseminated disease. In 9 of the deaths the thoracic component at presentations seems likely to be part of a generalised disease without definition of a primary site. Overall mortality in this series is 35% indicating the better prognosis of the patients presenting with thoracic neuroblastoma compared to other primary sites. If the 9 patients considered to have generalised disease are excluded then the mortality in this collected series is 22% (10 of 45). The investigations and management are outlined and the complications of therapy are considered.

The association of ovarian malignancy in children with maternal carcinogenesis.

The occurrence of malignancy in three mothers out of six girls presenting with malignant ovarian tumors is reported. The significance of this finding is discussed.

The changing incidence of neural tube defects in Scotland.

The impact of neural tube defects on neonatal surgery has been declining in Scotland over the past two decades. The Scottish statistics for neural tube defects were studied from 1971 to 1988. The incidence of neural tube defects in Scotland has declined from 5.50 to 1.10 per 1,000 births over this period (3.00 to 0.58 per 1,000 births for spina bifida and 2.50 to 0.52 per 1,000 births for anencephaly). Antenatal maternal alpha-fetoprotein (AFP) screening was introduced to Scotland on a wide scale in 1976. The number of terminations for anencephaly peaked in 1980 (85), and for spina bifida in 1981 (70), and both have since declined. The Scottish birth rate has been about 67,000 per year over this period. The declining incidence of neural tube defects is not explained by the effect of antenatal screening and terminations alone. A downward trend was apparent before 1976, and although antenatal screening has had a considerable impact on anencephaly births (peak terminations 89% in 1983), it has had only a modest impact on spina bifida births (peak terminations 53% in 1984). We conclude that the natural decline in incidence of neural tube defects is the major factor in the observed decline in neonatal surgical admissions for these defects.

A personal audit of pediatric surgical training before implementation of the Calman guidelines.

PURPOSE: The purpose of this study was to audit the surgical training experience of a Higher Surgical Trainee in the United Kingdom during the tenure of the posts of Career Registrar, Research Fellow, and Senior Registrar from August 1992 to July 1997. Although the Report of the Working Party on the UK Specialist Medical Training (the Calman report) was published during this study, the training remained the same because the author elected not to transfer to the new grade. METHODS: A 39-field database was designed, and the surgical experience was entered prospectively. The data were analyzed chronologically according to age of patient, condition, level of supervision, and nature of admission (emergency, elective). RESULTS: Two thousand two hundred ninety patients or operations are presented. Only a small number of patients underwent surgery during the research year (1994). The pattern of operating changed from one of large numbers of supervised to one of more major procedures. The numbers of neonates and younger infants who underwent surgery increased significantly, and the level of supervision changed allowing more autonomy toward the end of the training period. This trend was reversed partially during the period of overseas secondment. The results are compared with those in a recently published USA/Canadian study. CONCLUSION: The volume of work undertaken by the trainee ensures adequate exposure to a wide range of procedures to achieve a satisfactory level of competence. Changes that may affect this are discussed.

Congenital laryngotracheosophageal cleft.

Two infants with complete laryngotracheoesophageal cleft are presented. One infant had hypoplasia of the left bronchus and lung and the other had a cystic dysplastic right kidney. The literature is reviewed and a scheme for managing infants with this severe and as yet lethal anomaly is presented.