Biomedical subjects
Publications and source records attributed to J H Cross.
Clinical assessments of nutritional status in a group of 44 inpatients, made by a panel of experienced childcare specialists, were compared with anthropometric assessments. Assessors were uniformly poor at detecting severe malnutrition and at assessing the nutritional status of infants. Nutritional status cannot be accurately assessed clinically and anthropometry is crucial.
Clinical features, magnetic resonance, and biochemical studies are reported in 7 children with pyruvate dehydrogenase (PDH) deficiency. These findings confirm the diverse clinical presentation of this condition, although neurological abnormalities are consistent features. Imaging results are also varied. Six of the children were investigated with proton magnetic resonance spectroscopy and lactate was demonstrated in brain in all patients. Regional variation in the lactate signal was observed in those patients in whom 2 regions were examined. Advances in molecular genetics have provided some explanations for the clinical variation in pyruvate dehydrogenase deficiency.
We have been using proton magnetic resonance spectroscopy (1H MRS) in the investigation of adults and children with intractable epilepsy. Spectra were obtained from 2 x 2 x 2 cm cubes in the medial region of the temporal lobe, and were analyzed on the basis of signals from N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), and choline-containing compounds (Cho). In comparison with control subjects, the epilepsy patients as a group show significant reductions in the NAA signal and in the NAA/Cho+Cr ratio, with increases in the Cho and Cr signals. The reduction in NAA is interpreted in terms of neuronal loss or damage, while the increase in Cr and Cho signals may be a reflection of reactive astrocytosis.
Magnetic resonance imaging (MRI) can now provide maps of human brain function with high spatial and temporal resolution. We aimed to establish whether this noninvasive technique could also map the cortical activation that occurs during focal seizures. In order to do this, we used a conventional 1.5-tesla clinical MRI system for the investigation of a 4-year-old boy suffering from frequent partial motor seizures of his right side. We acquired FLASH images (TE = 60 msec) every 10 seconds over intervals of 10 minutes and derived activation images by subtracting baseline images from images obtained during clinical seizures. Functional MRI revealed sequential activation associated with specific gyri within the left hemisphere with each of five consecutive clinical seizures, and also during a period that was not associated with a detectable clinical seizure. The activated regions included gyri that were structurally abnormal. We concluded that functional MRI can provide new insights into the dynamic events that occur in the epileptic brain and their relationship to brain structure.
Congenital lactic acidosis form a large group of disorders that are commonly associated with profound neurological dysfunction. Difficulties are frequently encountered in establishing a diagnosis, and the mechanisms underlying brain damage are poorly understood. We have performed proton magnetic resonance spectroscopy (1H-MRS) on 24 patients under investigation for suspected metabolic disorder, and have compared the MRS observations of brain lactate with measurements of cerebrospinal fluid (CSF) lactate. We have shown good concordance between the two types of observation, confirming the value of the CSF measurements. Regional variations in brain lactate are detected in some cases, and these may help to elucidate the mechanisms underlying selective brain damage.
Hydrazine (HZ) and monomethylhydrazine (MMH) in air were monitored continuously using a hand-held ion mobility spectrometer equipped with membrane inlet, 63Ni ion source, acetone reagent gas, and ambient temperature drift tube. Response characteristics included detection limit, 6 ppb; linear range, 10-600 ppb; saturated response, >2 ppm; and stable response after 15-30 min. Ammonia interfered in hydrazines detection through a product ion with the same drift time as that for MMH and HZ. Acetone reagent gas was replaced with 5-nonanone to alter drift times of product ions and separate ammonia from MMH and HZ. Patterns in mobility spectra, ion identifications from mass spectra, and fragmentation cross-sections from collisional-induced dissociations suggest that drift times are governed by ion-cluster equilibria in the drift region of the mobility spectrometer. Practical aspects including calibration, stability, and reproducibility are reported from the use of a hand-held mobility spectrometer on the space shuttle Atlantis during mission STS-37.
The incidence of brain abnormalities determined by magnetic resonance in 30 consecutive children presenting with intractable complex partial seizures is reported. Images were optimised to visualise the hippocampus and cortical grey matter. Abnormalities of the hippocampus or temporal lobe were seen in all 19 children with clinical features of temporal lobe epilepsy and in six of the seven children with clinically unlocalised epilepsy. By contrast, in the four children with a clinical diagnosis of extratemporal epilepsy, no temporal or hippocampal abnormalities were seen. Generalised cortical abnormalities of uncertain significance were found in a total of 14 children from all groups. The identification of focal brain abnormalities using optimised magnetic resonance imaging enables early non-invasive assessment of children with intractable seizure disorders and the identification of patients for whom epilepsy surgery may be appropriate. It may also lead to a better understanding of the structural basis of intractable epilepsy, and thereby contribute to early treatment decisions.
We have performed localized in vivo proton magnetic resonance spectroscopy on two females with ornithine carbamoyl transferase deficiency during episodes of acute hyperammonemic encephalopathy with focal neurologic abnormalities. Spectra obtained from 2 x 2 x 2 cm cubic volumes at relatively long (135-ms) echo times contain additional signals that are characteristic of glutamine and indicate that glutamine is present in very high concentrations in the brain. The findings are consistent with the hypothesis that intracerebral accumulation of glutamine contributes to the encephalopathy associated with hyperammonemia. In one of the children, spectra obtained after treatment showed a marked decrease in the glutamine signals.
In 1991, we observed a Korean man infected by Capillaria philippinensis who had no history of traveling in known endemic areas. He had year-long diarrhea with severe loss of body weight. He enjoyed hunting and fishing and eating raw meat of game animals and fish. An open full-thickness biopsy of the ileum showed flat mucosal surface and sections of the round worm, and fecal examination revealed numerous elliptical helminth eggs. The worms and eggs were consistent with features of C. philippinensis. He was treated with albendazole and was cured. This is the first known case of intestinal capillariasis in the Republic of Korea.
There have been very few advances in epidemiological field techniques for filariasis in recent years. Advances in other areas of study of filariasis have been published and a summary of some of those which have some application to field technology will be given. Studies on vectors involving host influences on the development of filariae and the use of DNA probes for vector speciation were reported as well as the development of techniques that yielded species-specific identification of larvae in mosquito vectors. Experiments on animal transmission potentials also have been described. Mathematical models are becoming popular for various biological systems. It is postulated that models will enable workers to make predictions on prevalence of diseases and effect of control measures. A model has been proposed for bancroftian filariasis transmission dynamics and frequency distribution of microfilariae in blood samples. Other statistical methodologies have been published relating to age and sex distribution and frequency distribution and one suggested that females have increased resistance to filariasis, especially in the reproductive years. Advances in diagnostic technologies are highly relevant to the epidemiology of filariasis. The development of antibody and especially antigen detection systems using monoclonal antibodies, DNA probes, and polymerase chain reactions, etc, will make a significant impact on the identification of infected persons. Findings along other lines may also have application to field epidemiology. The quantitative blood count (QBC) acridine orange hematocrit tube has also been found to be of value in diagnosis. Elevated levels of ecdysteroids found in other filarial infections should be tested in cases of lymphatic filariasis.
Intestinal capillariasis caused by Capillaria philippinensis appeared first in the Philippines and subsequently in Thailand, Japan, Iran, Egypt, and Taiwan, but most infections occur in the Philippines and Thailand. As established experimentally, the life cycle involves freshwater fish as intermediate hosts and fish-eating birds as definitive hosts. Embryonated eggs from feces fed to fish hatch and grow as larvae in the fish intestines. Infective larvae fed to monkeys, Mongolian gerbils, and fish-eating birds develop into adults. Larvae become adults in 10 to 11 days, and the first-generation females produce larvae. These larvae develop into males and egg-producing female worms. Eggs pass with the feces, reach water, embryonate, and infect fish. Autoinfection is part of the life cycle and leads to hyperinfection. Humans acquire the infection by eating small freshwater fish raw. The parasite multiplies, and symptoms of diarrhea, borborygmus, abdominal pain, and edema develop. Chronic infections lead to malabsorption and hence to protein and electrolyte loss, and death results from irreversible effects of the infection. Treatment consists of electrolyte replacement and administration of an antidiarrheal agent and mebendazole or albendazole. Capillariasis philippinensis is considered a zoonotic disease of migratory fish-eating birds. The eggs are disseminated along flyways and infect the fish, and when fish are eaten raw, the disease develops.
A previously unrecognised and distinctive pattern of severe brain injury in extreme preterm neonates was observed recently. Fifteen neonates of birth weight 600-1270 g and gestation of 24-32 weeks showed relatively late development on cerebral ultrasound scan of extensive dense and cystic lesions involving the periphery of the brain. The extent of the changes was confirmed at postmortem examination in 11 babies. These changes have been called encephaloclastic porencephaly. The population of babies in whom this has occurred and their clinical outcome has been reviewed, with comparison between the evolution of the ultrasound changes and pathological findings at postmortem examination.
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DNA isolated from a newly described taeniid from Taiwan which shows adult characters indistinguishable from those of Taenia saginata was compared to DNA from T. saginata and nine other cestodes by restriction endonuclease digestion of genomic DNA and Southern blot analysis using 32P-labeled total cestode RNA and cloned ribosomal RNA gene fragments as probes. Hybridization patterns of Taiwan Taenia DNA revealed distinct variations from that of T. saginata and Taenia solium as well as all other cestode DNAs examined; however, similarities in restriction maps and sequence data between cloned ribosomal gene fragments from Taiwan Taenia (pTTr 3.1) and T. saginata (pTSgr 3.1 and PTSgr 2.4, respectively) suggest close evolutionary relatedness between these two taeniids. DNA sequence amplification from genomic DNA using oligonucleotide primers homologous to regions on both the 2.4- and 3.1-kb fragments was able to delineate between Taiwan Taenia and T. saginata by generating 1.0- and 0.29-kb fragments, respectively. Results demonstrated that Taiwan Taenia is not exclusive to Taiwan but exists in other parts of Eastern Asia and that adult morphology is insufficient for its detection in other locations. Results further support biological data indicating that Taiwan Taenia and T. saginata, although similar morphologically, are distinct genotypes.
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Fish from lagoons in Northern Luzon, Philippines, have been shown experimentally to be intermediate hosts of Capillaria philippinensis. Eggs ingested by the fish hatch in the intestines and the larvae double in size in 3 weeks. When fed to monkeys, Mongolian gerbils and birds, the larvae develop into adults and reproduce. Fish from the lagoons or purchased from the market were fed to gerbils and the animals developed patent infections, demonstrating natural transmission of the parasite. Philippine and Thailand populations have the habit of eating uncooked freshwater and brackish water fish and some have been experimentally infected with C. philippinensis. These countries report the largest number of cases of intestinal capillariasis. Fish-eating birds are now considered natural hosts for the parasite, fish the intermediate hosts, and humans accidentally become infected by eating infected fish.
What started out as an isolated report of an unknown intestinal parasitic disease has emerged as another disease of worldwide significance. Capillaria philippinensis was found in the intestines of a Filipino who suffered from an intractable diarrhoea and died in 1963. A few years later epidemics of intestinal cappillariasis erupted and spread to many parts of the Philippines. Thailand was also found to be endemic for the disease and in recent years, a few case reports have come from Japan, Iran and Egypt too. Since small freshwater and brackish water fish are considered to be the natural intermediate hosts, and fish-eating birds potential definitive hosts, John Cross suggests that the spread of the parasite may be attributable to migratory birds.
The birth weights of 13,351 babies born at full term from 1964-84 to Asian Moslem mothers in Birmingham were analysed to see if the effect of the Ramadan fast on maternal biochemical profiles was of any clinical relevance. These were compared with two age matched control groups comprising white and non-Moslem Asian babies. Ramadan had no effect on mean birth weight at whatever stage of pregnancy it occurred. There was an increase in the prevalence of low birth weights (4.5% to 8%) among babies who were born at full term when Ramadan had occurred during the second trimester, but this was not significant. We conclude that the Ramadan fast has no effect on the birth weights of babies born at full term.