bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe chronic neutropenia in Chinese children in Hong Kong
Authors: Leung TF , Li CK , Kwok KL , Chik KW , Shing MMK , Yuen PMP
Published: March 2003

Objective: Severe chronic neutropenia (SCN) is a rare and heterogeneous disorder in children. The epidemiology, clinical features and outcomes of SCN in Chinese children were reviewed.

Methodology: A retrospective analysis of case records was undertaken for 18 children with SCN managed during a 12‐year period in a university teaching hospital in Hong Kong.

Results: The median (range) age of the patients at initial presentation was 6.5 months (4 days–19 months). The initial and lowest median absolute neutrophil counts (ANC) were 0.29 × 109 /L and 0.06 × 109 /L, respectively. Patients with congenital SCN had significantly fewer neutrophils in peripheral blood at diagnosis. Only five subjects received granulocyte colony‐stimulating factor (G‐CSF) treatment. All children were free from serious infection on follow up for 51 months. Only one child suffered from long‐term infection‐related morbidity. One patient with chronic neutropenia was subsequently shown to have common variable immunodeficiency.

Conclusions: Most children with SCN in our series had favourable clinical outcomes. Our results support the recommendation that G‐CSF should be used only in those with recurrent or severe infections.
Deceptive hyperbilirubinaemia in a newborn with familial lipoprotein lipase deficiency
Authors: Ng PC , Lam CWK , Fok TF , Lee CH , Lo DYM , Chan LYS , Sin NC , Packard CJ
Published: March 2003

Abstract: A rare case of familial lipoprotein lipase (LPL) deficiency in a Chinese newborn who presented with severe hyperbilirubinaemia is described. The falsely high serum bilirubin concentration was subsequently found to be a laboratory analytical error caused by interference of optical measurement of the lipaemic serum. Hypertriglyceridaemia and chylomicronaemia could be safely and effectively controlled by a fat‐restricted diet using either modified elementary milk formula fortified with protein, calories and minerals, or the commercially available special milk formula such as Monogen or Portagen. DNA sequence analysis of the patient showed a Leu252Arg mutation in exon 6 of both alleles of the LPL gene. Although the parents were unrelated, both were heterozygous carriers of the same genetic defect. Codon 252 in exon 6 appears to be a common and critical site of mutation in the LPL gene of Chinese, but this important association has not been recognized previously.
Meningococcal disease and vaccination in North America
Authors: Pollard A J , Scheifele D
Published: March 2003

Abstract: In North America, meningococcal disease occurs at a rate of 1 case per 100 000 population per year, producing 2725 cases notified in the US in 1998 and 155 laboratory confirmed cases in Canada in the same year. A majority of these cases occur in the winter season and in early childhood, with a case fatality rate of approximately 10%. There has been an increase in the proportion of cases due to serogroup Y meningococci over the past decade: in 1995–98 in the US, 33% of cases were due to serogroup B, 28% were due to serogroup C and 34% were due to serogroup Y; in Canada in 1995–96, 47% of cases were due to serogroup B, 40% were due to serogroup C and 10% were due to serogroup Y. Outbreaks due to serogroup C were more common in the 1990s in the US and a number of outbreaks have occurred in Canada due to organisms from the hypervirulent ET‐37 complex. College freshmen in the US in dormitories were found to be at an increased risk of disease. In addition, over the past 10 years, an outbreak of serogroup B disease occurred in the Pacific North‐west of the US, with a fourfold increased rate of disease in that region. The explanations for these changes in epidemiology are unknown, but probably reflect the appearance of hypervirulent clones of meningococci and/or changing levels of population immunity. Meningococcal serogroup C polysaccharide–protein conjugate vaccines have been introduced recently in the UK, seem efficacious and offer the potential to reduce the burden of disease in the US and Canada too. Because serogroups other than serogroup C are prevalent in North America, a combination polysaccharide–protein vaccine, including C, Y and possibly W135 serogroups, would be attractive for this population. Although not currently an issue in industrialized nations, inclusion of serogroup A conjugates in any future vaccine policy would be an important decision in driving global prevention of meningococcal disease. A meningococcal conjugate vaccine against serogroup C was licensed in Canada in April 2001.
Epidemiology of meningococcal disease in Australia
Authors: Jelfs J , Munro R
Published: March 2003

Abstract: A review of the epidemiology of meningococcal disease (MD) in Australia was undertaken, with particular emphasis on the 1990s, when national strain differentiation data became available. The data included a review of clinical and laboratory notification data and published reports on clusters and outbreaks. There have been considerable changes in the patterns of MD in the 1990s. In some cases, these changes can be related to the dominance of a particular phenotype. In the early 1990s, widely scattered urban and rural clusters were associated with the phenotype C:2b:P1.2 and strains were closely genetically related. Larger urban clusters and increased numbers of cases in adolescents and young adults were most obvious in New South Wales in the mid‐1990s and were associated with a phenotype C:2a:P1.5. This ET‐15 clone of the ET‐37 complex caused similar patterns of MD to those seen in other countries as part of the global spread of the clone. In contrast, the B:4:P1.4 phenotype, with close genetic similarities to New Zealand strains, did not cause the hyperendemic disease seen in New Zealand this decade. The epidemiology of MD will continue to exhibit considerable variation due, at least in part, to the genetic flexibility of meningococci. Information about strain variation expands our understanding of changing patterns of disease.
Inspired gas temperature during mechanical ventilation: Effects of environmental temperature and airway temperature probe position
Authors: Todd DA , Boyd J , Lloyd J , John E
Published: March 2003

Objectives: To determine the inspired gas temperature during mechanical ventilation with: (i) five different humidicrib temperatures; (ii) two airway temperature probe (ATP) positions; and (iii) four ATP adaptors.

Methodology: An observational study in the Neonatal Intensive Care Laboratory, Westmead Hospital. The inspired gas temperature was measured at the proximal end of the endotracheal tube (ETT) during conventional mechanical ventilation using a Tele‐thermometer. Inspired gas temperature measurements were made with: (i) the humidicrib temperature set at 30.8, 32.9, 35.2, 36.2, or 37.2°C; (ii) the ATP either (A) positioned inside the humidicrib at the distal end of the inspiratory tubing or (B) positioned outside the humidicrib 50 cm proximal to the ETT, with the inspired gas temperatures set at 36.5 and 39.0°C, respectively; and (iii) the measurements repeated with four different ATP adaptors at each humidicrib temperature and each ATP position.

Results: With the ATP inside the humidicrib, there were no significant differences between set and actual inspired gas temperature. However, with the ATP outside the humidicrib, there were significant decreases in inspired gas temperature at each humidicrib temperature. For instance, with the ATP outside the humidicrib and set at 39.0°C, the inspired gas temperature decreased to 34.7 ± 0.2°C at a humidicrib temperature of 30.8°C and to 37.7 ± 0.2°C at a humidicrib temperature of 37.2°C. The type of ATP adaptor also had a significant effect on inspired gas temperature.

Conclusions: With the ATP placed outside the humidicrib and with variations of humidicrib temperature, infants are likely to have inspired gas temperatures that are significantly different to the desired temperature. Certain ATP adaptors cause these variations in inspired gas temperature to be more pronounced. Extreme care must be used to avoid suboptimal inspired gas temperatures with these environmental variations and the ATP positioned outside the humidicrib.
Penetrating injuries in children: Is there a message?
Authors: Holland AJA , Kirby R , Browne GJ , Ross FI , Cass DT
Published: March 2003

Objectives:  To determine the frequency, management and outcome of penetrating trauma in children.

Methods:  A retrospective review of penetrating injuries in children under 16 years of age admitted to the Children's Hospital at Westmead (CHW), and deaths reported to the New South Wales Paediatric Trauma Death (NPTD) Registry, from January 1988 to December 2000. Patient details, circumstances of trauma, injuries identified, management and outcome were recorded.

Results:  Thirty‐four children were admitted to the CHW with penetrating injuries during the 13‐year period. This represented 0.2% of all trauma admissions, but 3% of those children with major trauma. The injury typically involved a male, school‐age child that fell onto a sharp object or was assaulted with a knife or firearm by a parent or person known to them. Twenty‐five children (75%) required operative intervention for their injuries and 14 survivors (42%) suffered long‐term morbidity. Thirty children were reported to the NPTD Registry over the same interval, accounting for 2.3% of all trauma deaths in New South Wales. Of these, a significant minority was injured by falls from a mower or a tractor towing a machine with blades.

Conclusions:  Penetrating injuries are uncommon, but cause serious injury in children. There are two clear groups: (i) those dead at the scene or moribund on arrival, in whom prevention must be the main aim; and (ii) those with stable vital signs. Penetrating wounds should be explored in the operating theatre to exclude major injury. Young children should not ride on mowers or tractors.
Primary cardiac tumours in a paediatric population
Authors: Elderkin RA , Radford DJ
Published: March 2003

Objective: To review the presentation, diagnosis, histology and outcome of primary cardiac tumours presenting to a paediatric cardiac unit over a 20‐year period.

Methods: Hospital records and data bases were searched for the years 1980–2000.

Results: There were 12 patients with four histological tumour types including
a predominance of rhabdomyoma, as well as myxoma, fibroma and myocardial hamartoma.
Diagnosis was made in utero, by ultrasound in five cases and in the neonatal
period in a further three cases. Six cases (50%) required surgical intervention
and there were three tumour‐related deaths. Two infants with large left ventricular
tumours diagnosed in utero developed univentricular physiology, acting like hypoplastic left heart syndrome at birth.

Conclusions: Despite an absence of malignant histology there was significant mortality and morbidity among the patients reviewed. The development of univentricular physiology in infants with large left ventricular tumours is rare and is a difficult management problem.
Sedation practices for Australian and New Zealand paediatric oncology patients
Authors: Barnes C , Downie P , Chalkiadis G , Camilleri S , Monagle P , Waters K
Published: March 2003

Objectives: Paediatric oncology patients often require repeated bone marrow aspirates and lumbar punctures. These procedures commonly require sedation and analgesia. The Australian and New Zealand College of Anaesthetists and the American Academy of Pediatrics have published guidelines that provide recommendations on monitoring and staffing requirements during sedation of paediatric patients. A survey was conducted of the oncology units in Australia and New Zealand in order to compare current practices with published guidelines.

Methods: Telephone interviews were conducted with nursing or medical staff members.

Results: Fourteen oncology units collectively perform approximately 130 procedures each week, of which 74% are performed under general anaesthesia. Of the remainder, most are performed using conscious sedation. Most units adhere to published recommendations regarding equipment and staffing during procedures performed under sedation. Only a minority of units follow guidelines regarding documentation; fasting requirements; observation and documentation of vital signs during and after the procedure; and obtaining informed consent for procedures performed using sedation.

Conclusion: Sedation practices among paediatric oncology units in Australia and New Zealand vary. None of the units fully adhere to published guidelines on childhood sedation. Paediatric oncology units should be familiar with the content of these guidelines and make an informed decision as to their usefulness, both in directing best clinical practice, and in supporting current practice in the event of medico‐legal challenge.
Rehabilitation of spasticity and related problems in childhood cerebral palsy
Authors: Flett PJ
Published: March 2003

Spasticity is one part of the upper motor neuron syndrome, but it is a widespread problem in cerebral palsy; it is debilitating, affects function and can lead to musculoskeletal complications. Significant advances have occurred in antispasticity management (and related musculoskeletal problems) in children with cerebral palsy during the past 5−10 years. Botulinum toxin A has been the most outstanding treatment advance; it is relatively long‐lasting, easy to administer, reversible, has a favourable side‐effect profile and is highly useful for focal spasticity. There is an emerging role for intrathecal baclofen in Australia. Despite being available and practised in North America for years, selective dorsal rhizotomy has not been popular in Australia. The use of orthopaedic surgery has significantly altered in recent years. There is still a place for oral drug treatment, including some newer agents and the potential for combination treatment with other modalities. The role of physical therapy in defining disability, assessing function, undertaking biomechanical assessment and providing mobility aids/casting/orthoses and motor training/stretching exercises is critical for the success of medical and surgical interventions. From an Australian perspective, the purpose of the present review is to provide a critical review of therapies available for spasticity associated with childhood cerebral palsy.
Extended paediatrics: Acute care in children’s homes
Authors: Sherring Michael Anthony
Published: March 2003

Abstract The Extended Paediatric Service was established in 1996 to provide acute care services to children in their homes with the aim of reducing the number of hospital admissions for children and shortening hospital stays while maintaining continuity of care. Extended Paediatrics builds on, and extends, the principles of Discharge Liaison and Hospital In The Home programmes. The service is staffed by nurses who also work within the paediatric ward of the Launceston General Hospital, providing a high degree of continuity of care for these children. Children are admitted to the service through consultation between medical staff, nursing staff and the child’s family. Between August 1996 and December 1999 a total of over 1200 visits to 48 children have been made for various treatments, for tests, education or follow up. Improved outcomes for children and their families have been reported by both staff and parents as a result of the service.
The quality of medical laboratory practice in Trinidad and Tobago, West Indies
Authors: Ezenwaka Chidum E
Published: March 2003

Abstract The introduction of automated chemical analyzers in the laboratory service has the potential of adversely affecting professionalism in laboratory practice. The present study assesses the quality of medical laboratory technicians in Trinidad and Tobago using structured questionnaires. Some of the critical questions included job status, years of experience, training, qualification(s) and knowledge of quality assurance and its application. About 82% of laboratory technicians responded to the study. The majority of technicians (62%) had diploma certificates while only one (1.2%) had a postgraduate degree. Although the majority (91.7%) of technicians knew about quality assurance, 36% learnt on the job and 59% knew they were not professionally trained. The results showed that there is paucity of highly trained laboratory technicians in Trinidad and Tobago and this has significant implications on the technical initiative and quality of medical laboratory practice in this country. We recommend the establishment of appropriate professional institutions for training medical laboratory technologists and regular expert inspection and accreditation of all medical laboratories in the country.
The benefits of using clinical pathways for managing acute paediatric illness in an emergency department
Authors: Browne Gary J , Giles Helen , Mccaskill Mary E , Fasher Bruce J , Lam Lawrence T
Published: March 2003

Abstract The aim of this study was to provide an evaluation of the overall effectiveness of using a number of clinical pathways in treating common acute paediatric conditions in an emergency department. This was a before and after study conducted on the effectiveness of three clinical pathways (gastroenteritis, asthma, and croup) in the emergency department of the Children’s Hospital at Westmead, conducted over two separate yearly periods January to December 1996 and January to December 1999 representing before and after the introduction of clinical pathways in the emergency department. The main outcomes of the effectiveness of the pathways, namely admission to an in‐patient bed, length of hospital stay and re‐presentation after discharge from the ED were compared. Other outcomes of interest such as parental satisfaction and patient waiting times were also presented. Any deviation from a key clinical pathway process was reported. A total of 2854 children were managed by a clinical pathway compared to 2680 children managed before clinical pathways were introduced. The admission rate was reduced by threefold (9.1% compared to 23.6%) with a twofold reduction in length of hospital stay (32.7 h compared to 17.5 h). In 3.6% of children using a clinical pathway an unscheduled medical visit or re‐presentation to the emergency department occurred after discharge, compared to 4.9% before the use of clinical pathways. No adverse events were reported in these children. In 76 cases deviation from a clinical pathway process was reported. High parental satisfaction was reported for clinical pathways throughout the study. Clinical pathways in this emergency department allowed rapid stabilisation of children, reducing admission rate, with a shortened length of hospital stay and few patients re‐presenting after discharge and were well accepted by parents.
Rational prescribing for childhood pneumonia
Authors: Dawson Kenneth P
Published: March 2003

AbstractThe aim of this study was to assess the management and prescribing patterns for community acquired pneumonia in children in a provincial hospital setting and, further, to discover the evidence on which treatment choices were made and ascertain the need for management guidelines. The method employed was to obtain the relevant data by a retrospective audit of the case notes of children admitted with pneumonia to Wairau Hospital, Blenheim, New Zealand. The findings indicated that there were 12 different treatment regimens employed. There appeared to be no rational basis for the choices made and no microbiological evidence to support the frequent use of broad spectrum antibiotics. No difference in clinical efficacy was found between the main regimens used. It is concluded that a simple management protocol for childhood pneumonia using a narrow spectrum antibiotic initially would be as effective, more logical and cheaper.
Recovery after stroke: A qualitative perspective
Authors: O’Connell Bev , Hanna Barbara , Penney Wendy , Pearce Julian , Owen Martin , Warelow Phil
Published: March 2003

Abstract The purpose of this study was to determine the impact of stroke on survivors of the condition and to identify their physical and psychosocial needs in rural and regional settings. Data were collected via focus group interviews with stroke survivors, carers and key informants. Data were managed using NUD*IST and analysed using a content analysis method identifying major themes related to the impact of living in the community after having a stroke. It was found that stroke survivors suffered severe physical and emotional effects. The findings also identified the vulnerability of this group and a lack of organised, on‐going psychosocial and rehabilitative support. Recommendations are made to enhance the current management of stroke after the acute and subacute phases.
Limnology and pollution of a small, shallow tropical water‐body (jagüey) in North‐East Mexico
Authors: Zavala Elia Hoz , Espino Guadalupe de la Lanza
Published: March 2003

The environmental characteristics and degree of pollution of a jagüey (a small, shallow tropical water‐body) in Mexico were identified by means of an environmental impact matrix. Jagüeys are important as their main sources of water are the subsurface water‐table and rainfall, however, they have not been studied because of their small size. A flow diagram was designed to incorporate the main climatic, geological and hydrological environmental factors, as well as physico‐chemical data on sediment and water qualities, and biological, technostructural and socioeconomic aspects. The resulting index of –90 in the environmental impact matrix indicates a severe negative impact on jagüeys from the input of allochtonous nutrients because of their small depth, limited circulation and the high rate of evaporation. The jagüeys studied appear in a state of hypertrophy and senility, despite geological youth.
Importance of sustainable management of percolation lakes in semiarid basaltic terrain in western India
Authors: Limaye Shrikant D.
Published: March 2003

Sustainable management of percolation lakes or percolation tanks is closely related to the survival of approximately 15 million farmers and an equal number of cattle living in the semiarid basaltic plateau of western India. Here, the monsoonal rains are restricted to a few rainy days between June and September. It is therefore necessary to harvest the monsoon runoff into small percolation lakes in mini‐catchments by constructing earthen bunds on small streams and allowing the stored water in the lakes to percolate and recharge the groundwater body. The residence time of water in the mini‐catchments is thus increased and it is possible for the farmers to dig wells and irrigate the crops in their small farm plots. The efficiency of the percolation lakes is hampered by silt that accumulates in the lake bed or tank bed, year after year. It is therefore necessary for the beneficiary farmers to desilt the lakebed when the lake dries in the summer. Soil conservation practices should be followed in the catchment area in order to reduce the amount of silt entering the lake. Non‐governmental organizations play an important role in this field.
Management issues of the Lake Peipsi/Chudskoe region
Authors: Kosk Aija
Published: March 2003

Lake Peipsi is the fourth largest lake in Europe and the largest international lake in Europe. Lake Peipsi is shallow, eutrophic, biologically very productive and is bordered by many wetland areas along its coasts. Large peat deposits in the Lake Peipsi basin are protected under national legislation. The lake is most important as a resource for recreation and fisheries. The fish stock in Lake Peipsi is one of the richest in Europe. The most critical environmental issues for the Peipsi watershed are eutrophication and unregulated fishing in the lake. During the Soviet period, large collective farms dramatically accelerated eutrophication. Despite the drop in fertilizer use during the last 10 years and a decrease in the number of domestic animals in the watershed, the impact of the earlier agricultural pollution is still significant. Untreated sewage has also been dumped in the Narva River tributary as a result of an international dispute concerning water supply and wastewater treatment. People living in the Lake Peipsi region have faced traumatic changes as a result of the re‐establishment of the border between Russia and Estonia in 1992. The establishment of an international border on the waters of the lake has resulted in fishermen losing access to many of their traditional fishing areas. Political and economic transformations of the last 10 years have seriously interrupted information exchange between different institutions and organizations concerned with the health of the lake. The Centre for Transboundary Cooperation facilitates international communication and cooperation between the Estonian and Russian governments and promotes public participation in environmental, social and economic development and decision‐making. The centre is in the process of guiding the development of a watershed management plan for the Lake Peipsi watershed and a vision for watershed development that is truly sustainable.
Influence of artificial reefs on fish assemblage of the Barra Bonita Reservoir (São Paulo, Brazil)
Authors: Freitas Carlos E. C. , Petrere Miguel
Published: March 2003

This paper deals with the effects of introduced artificial reefs on the diversity of freshwater fish communities in lentic and lotic zones of a very impacted river in southeastern Brazil. To accomplish this goal, artificial reefs were introduced, in December 1997, in the Barra Bonita reservoir and in the lotic zone immediately below the dam. Fish diversity was always higher in the lotic zone than in the reservoir. Accordingly, fish diversity near the artificial reefs was consistently higher than in the control areas. We propose that the higher environmental complexity in the lotic zone, as compared to the reservoir, is incremented in areas where artificial reefs were introduced; also, we present that, in both areas, diversity is mainly affected by the introduction of artificial reefs.
Detection and variation of microcystin contents ofMicrocystisblooms in eutrophic Lalla Takerkoust Lake, Morocco
Authors: Oudra B. , Loudiki M. , Sbyyaa B. , Sabour B. , Martins R. , Amori A. , Vasconcelos V.
Published: March 2003

Hepatotoxic microcystins produced by cyanobacteria represent a significant health hazard. In Morocco, although blooms of cyanobacteria are known to occur frequently in some water‐bodies, studies on toxicology and toxinology of these potentially harmful algae have been scarcely developed. This paper presents results of the detection of Microcystin‐LR (Mcyst‐LR) and other microcystin variants and their content variations fromMicrocystisnatural blooms and from the isolated strain culture. During the cyanobacteria dynamic study, 11 bloom samples were collected between 1994 and 2000 and were assessed for toxicity and quantification of microcystins, respectively, by mice bioassay and the enzyme‐linked immunosorbent assay. The bloom samples exhibit a high toxicity with mice intraperitoneal injection (i.p.) LD50< 100 mg/kg and the total microcystin contents were 496–8800 μg/g dry weight with a coefficient of variation of less than 11%. However, theMicrocystisisolated strain cultured on Z8 medium under controlled laboratory conditions produced an amount of 707 μg/g dry weight, its toxicity level corresponds to a LD50i.p mice of 31 mg/kg. The detection of microcystin variants and the identification of Mcyst‐LR from some natural bloom samples collected in 1994, 1996 and 1999 have been carried out by high performance liquid chromatography with a photodiode array detector, which confirmed the identification from each bloom sample of at least four microcystin variants, among which the Mcyst‐LR one represents a relative proportion of 30% to 62% of total microcystin contents. Only one variant of microcystin that was not a Mcyst‐LR has been detected from aMicrocystisisolated strain. The toxicity level of the material depended either on the amount of microcystins or the number of these variants and their proportion. According to these results, the survey of cyanobacteria and cyanotoxins monitoring in water used for human consumption is needed to avoid any sanitary risk.
Multifocal glial nodules in a case of Duchenne muscular dystrophy with severe mental retardation
Authors: Itoh Kyoko , Jinnai Kenji , Tada Kazuo , Hara Kiyokazu , Itoh Hiroshi , Takahashi Keiichi
Published: March 2003

A case of Duchenne muscular dystrophy with multifocal hamartomatous glial nodules in the cerebral cortex is reported. The patient had suffered severe mental retardation since boyhood, dying of aspiration pneumonia at the age of 23 years. Post‐mortem examination revealed an atrophic brain with normal gyri. Microscopically, multifocal small nodules composed of bizzare astrocytic cells, multinucleated cells, neuron‐like cells, small astrocytes and glial fibers were found in the first, fifth and sixth layers of the prefrontal cortex. Some of the bizarre cells showed intense immunoreactivity for glial fibrillary acidic protein and moderate to very weak reactivity for ubiquitin, tau protein and αB crystallin but no immunoreactivity for neurofilament and synaptophysin, suggesting that these cells were of astrocytic origin. The nodules were considered to be due to hamartomatous changes that had occurred in the early stage of brain development, and that might have been partly responsible for the pathogenetic mechanisms of mental retardation.
Immunohistochemical localization of lysosomal cysteine protease cathepsins B and L in monkey hippocampal neurons after transient ischemia
Authors: Kohda Yukihiko , Tsuchiya Katsuhiro , Yamashita Junkoh , Yoshida Masaki , Ueno Takashi , Yoshioka Tohru , Kominami Eiki , Yamashima Tetsumori
Published: March 2003

The mechanism by which hippocampal neurons are selectively vulnerable to ischemic injury remains unclarified. Neuronal lysosomes are known to contain the cysteine protease cathepsins, which may be involved in the mechanism of delayed neuronal death. In this study, the expression and localization of cathepsins in the postischemic hippocampal neurons of the monkey were examined. Enzymatic activities and protein levels of cathepsins B and L were increased after ischemia in both the vulnerable CA1 sector and the remaining resistant sectors. Immunohistochemical analysis suggested that lysosomal enzymes of CA1 were localized mainly in the neuropil and not in the neuronal cell bodies, while the enzymes of CA2–4 sectors were located within the neurons and associated with the perinuclear lysosomal granules. Thus, it was concluded that distributional differences of cathepsins B and L after transient ischemia could be related to selective CA1 neuronal death in the hippocampus.
Hemangioblastomas: Immunohistochemical and ultrastructural study of the stromal cells
Authors: Tashiro Yoshihiko , Iwata Yasushi , Takeno Yoshiaki , Tomonaga Masamichi , Sueishi Katsuo
Published: March 2003

An immunohistochemical study of 36 hemangioblastomas (Hmbl) from 32 patients was performed to clarify the cytogenesis of stromal cells (SC). In 19 of 29 Hmbl, SC revealed glial fibrillary acidic protein‐immunolabeling with an antigen retrieval by trypsinization, and were also positive for S‐100 protein, αB crystallin, neuron‐specific enolase and vimentin. Ultrastructurally, SC contained lipid droplets, unevenly distributed intermediate filaments with occasional myelin figures, primitive desmosomal junctions and, although rare, Rosenthal fibers or a cilium. It is concluded that SC associated with Hmbl exhibit markers consistent with an astrocytic origin.
Ultrastructural characterization of brain tumors using collagen gel culture
Authors: Yamada Akifumi , Tsuchida Takahiro , Yamanouchi Yasuo , Kawamoto Keiji
Published: March 2003

In an attempt to investigate the tumor type‐specific ultrastructure of cultured brain tumors, collagen gel culture was utilized instead of the conventional monolayer culture. In order to avoid intermingling of the normal brain cells, tumors with a clear margin were chosen. The tumors were cultured first in the monolayer culture for a few passages, and then tumor cell pellets were prepared and embedded in the collagen gel. In the event that tumors failed to grow in the monolayer culture, small fragments of tumor tissue were embedded. Ultrastructurally, the tumor cell processes of central neurocytoma contained numerous dense‐core vesicles. The formation of desmosomes was observed in the meningioma cell processes. The development of polypoid microvilli similar to those of the normal choroid plexus epithelium was observed in a case with ependymoma. A continuous basement membrane was seen surrounding the tumor cell processes facing the collagen gel in two ependymomas. These findings suggest the usefulness of the collagen gel culture in analyzing the tumor type‐specific ultrastructure of cultured brain tumors and possibly in studying cellular differentiation.
Relative preservation of GABAA receptor β‐subunit immunoreactivity in the hippocampus in mesial temporal sclerosis
Authors: Honavar M , Everall Ip , Meldrum Bs
Published: March 2003

The pattern of cell loss and changes in the expression of inhibitory and excitatory receptors in the subzones of the hippocampus in patients with pharmacoresistant (drug‐refractory) complex partial seizures was studied. Neuronal densities were measured in the mid‐hippocampus in temporal lobectomy (n = 10) and total hemispherectomy (n = 2) specimens from 12 patients with mesial temporal sclerosis (MTS), in temporal lobectomy (n = 6) and hemispherectomy (n = 5) samples from 11 epileptic patients without MTS, and in six autopsy brains from patients without neurological disease. No differences in hippocampal cell densities were found between the autopsy and the non‐MTS group. The MTS group, compared with the non‐MTS or the autopsy group, showed a 95% decrease in neuronal density in CA1, a 70% decrease in cornu ammonis (CA)2, an 85% decrease in CA3, and an 80% decrease in CA4. The proportion of neurons staining positively with a polyclonal antibody for the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole proprionic acid (AMPA) glutamate receptor subunits GluR2 and GluR3 was increased to 32% in the CA1 region in the MTS group, compared with 21% in the non‐MTS hippocampi. This difference was, however, just at the level of statistical significance (P = 0.054). Elsewhere in the hippocampus no significant change was observed. By contrast, the proportion of cells staining positively with a monoclonal antibody to the β‐subunit of the GABAA benzodiazepine (BZ) receptor was markedly increased in the MTS hippocampi, from 13% in non‐MTS CA1 to 50% in MTS CA1 region; and from 26% in non‐MTS CA3 to 63% in MTS CA3. Although previous studies (in vivo and ex vivo) have emphasized a loss of BZ receptors in temporal lobe epilepsy, this study shows that the expression of the GABAA receptor immunopositive population appears to be increased relative to the neuronal density.
Nasu–Hakola disease: A review of its leukoencephalopathic and membranolipodystrophic features
Authors: Tanaka Junichi
Published: March 2003

The clinicopathological features of Nasu–Hakola disease are described by reviewing previously reported cases and adding consideration to newly disclosed evidence. This disease is an autosomal recessive disorder characterized by membranocystic lipodystrophy in the skeletal system and sclerosing leukoencephalopathy in the nervous system. The leukoencephalopathic alterations are demyelinization of the cerebral white matter, associated with conspicuous fibrillary gliosis and preservation of the subcortical arcuate fibers. Sudanophilic granules are focally scattered in the perivascular space or widely infiltrated in the affected white matter, and some neuronal loss with deposits of calcospherites is encountered in the basal ganglia and also in the thalamus. Spheroid formation with an increased number of neurofilaments in the neuronal axon is considered a possible pathogenesis, and a primary vascular mechanism is also suggested. Interestingly, most of the reported cases of Nasu–Hakola disease are from Japan and Finland which suggests heredofamilial background as a cause.
Are pathological lesions in neurodegenerative disorders the cause or the effect of the degeneration?
Authors: Armstrong Richard A , Cairns Nigel J , Lantos Peter L
Published: March 2003

Pathological lesions in the form of extracellular protein deposits, intracellular inclusions and changes in cell morphology occur in the brain in the majority of neurodegenerative disorders. Studies of the presence, distribution, and molecular determinants of these lesions are often used to define individual disorders and to establish the mechanisms of lesion pathogenesis. In most disorders, however, the relationship between the appearance of a lesion and the underlying disease process is unclear. Two hypotheses are proposed which could explain this relationship: (i) lesions are the direct cause of the observed neurodegeneration (‘causal’ hypothesis); and (ii) lesions are a reaction to neurodegeneration (‘reaction’ hypothesis). These hypotheses are considered in relation to studies of the morphology and molecular determinants of lesions, the effects of gene mutations, degeneration induced by head injury, the effects of experimentally induced brain lesions, transgenic studies and the degeneration of anatomical pathways. The balance of evidence suggests that in many disorders, the appearance of the pathological lesions is a reaction to degenerative processes rather than being their cause. Such a conclusion has implications both for the classification of neurodegenerative disorders and for studies of disease pathogenesis.
Validation of a new analytical model for peritoneal transport model using rabbit in vivo experimental data
Authors: Hamada Hiroyuki , Sakiyama Ryoichi , Yamashita Akihiro C. , Okamoto Masahiro , Tojo Kakuji J. , Kumano Kazuo , Sakai Tadasu
Published: March 2003

SUMMARY:

Computer simulation techniques may be useful for considering an appropriate treatment schedule for peritoneal dialysis by using a mathematical model. The authors derived a new approximated analytical solution for Pyle‐Popovich’s peritoneal dialysis model that is known to simulate peritoneal transport quantitatively. In the present study, the validity of the new model was demonstrated by comparing it with another approximated analytical solution derived by other researchers using rabbit in vivo experimental data taken under normal continuous ambulatory peritoneal dialysis (CAPD) mode. The new model showed much better agreement with the experimental data no matter how the plasma concentration changed during the course of the experiment. The new analytical solution can simulate the change of metabolite concentration in the plasma using clinical data at an arbitrary treatment time.
Mid‐term effects of steroid therapy on childhood‐onset IgA nephropathy
Authors: Watanabe S , Hattori M , Akioka Y , Yamaguchi Y , Ito K
Published: March 2003

Purpose: IgA nephropathy (IgAN) is considered the most common glomerular disease in the world. Although treatment of children with severe IgAN with predonisolone (PSL) has been reported, the mid‐term prognosis of paediatric patients treated with PSL is unclear. In the present study we examined the mid‐term effects of PSL therapy.

Method: Thirty‐seven paediatric patients with IgAN (18 males, 19 females), whose biopsy findings showed acute segmental lesions including cellular crescent and adhesion in more than 10% of glomeruli examined, were prospectively treated with PSL plus heparin‐warfarin and dipyridamole (Tx) for 1.5 years and followed up over 1 years after Tx end. Fifteen age and histological grade‐matched children with IgAN (six males, nine females), who had never been treated with PSL, were also evaluated as a historical control. The mean observation period was 5.0 ± 1.8 years (range, 2.5–8.6 years). The histological grade (acute lesion) and stage (chronic lesion) were scored semiquantitatively based on the Shigematsu’s grade‐stage system.1

Result: Proteinuria decreased 1.48 g/day/1.73 m2 at the start of Tx to 0.32 g/day/1.73 m2 at the end of Tx. Eighteen patients (48.6%) achieved complete remission (CR). No patient developed chronic renal failure in Tx group, while two of the controls deteriorated renal function in the last observation. The pattern of responsiveness to Tx were divided into three groups according to the levels of proteinuria: CR, rebound (> 0.5 g/day/1.73 m2) and incomplete remission (< 0.5 g/day/1.73 m2). The rebound of proteinuria is usually accompanied with PSL reduction. The grade of glomerular pathology was improved with Tx (Gg: 0.8–0.3), while the stage of tubulo‐interstitial change progressed (Sint: 0.7–1.2).

Conclusions: The present study shows that Tx to children with IgAN showing acute lesions for 1.5 years is effective to subside acute glomerular injury. However, because clinical courses of treated patients vary in each patient, dosage and duration of PSL administration should be modified in their clinical setting.
Long‐term evolution of renal histology in slowly progressive patients with IgA nephropathy
Authors: Abe A , Kawamura T , Utsunomiya Y , Hamaguchi A , Kitajima T , Hosoya T
Published: March 2003

Recent clinical trials indicate that non‐immunological mechanisms (e.g., glomerular hypertension or hypertrophy) may play a crucial role in the progression of patients with IgA nephropathy. Since the long‐term renal histological changes in an individual patient with IgA nephropathy are not well elucidated, we assessed the serial renal biopsy specimens from nine patients with IgA nephropathy (five males, four females) where serial biopsies were performed in an interval of more than 10 years (mean 12.8; range 10–20). Histological parameters (i.e. percentage of global sclerosis (GS), tubulo‐interstitial lesion (TI), patients (Pt) with cellular crescent (CC) or arteriolosclerosis (AS), mean glomerular area (MGA) and number of glomeruli per renal cortical area (glomerular density, GD)), were compared between the both specimens (Table 1).

Renal biopsy
Age (year)
Pt with HT (%)
UprV (g/day)
Ccr (mL/min)
GS (%)
Pt with CC (%)
MGA (× 103μmm)
GD (/mm2)
Pt with AS (%)
TI (%)

First
25 ± 8
22
0.6 ± 0.3
88 ± 17
10 ± 11
78
15 ± 6.0
3.9 ± 2.0
11
13 ± 8

Second
38 ± 8
78*
1.3 ± 0.6*
55 ± 21*
25 ± 23
11*
22 ± 8.4*
2.0 ± 0.8*
89*
34 ± 16*

Mean ± SD, *P < 0.05 vs first biopsy

All patients had a slowly progressive course between the first and second biopsies as evidenced by the significant difference in the percentage of hypertension (HT), urinary protein excretion (UprV) and creatinine clearance (Ccr). Histological analysis of serial biopsy specimens revealed that the degrees of AS and TI were significantly enhanced at second biopsy, while acute glomerular lesions such as CC were remarkably diminished. Of note, a marked increase in MGA as well as a significant reduction in GD were observed during over 10 years. Moreover, at second biopsy, the values for MGA from individual patients negatively correlated with those for GD (r = 0.77, P < 0.01) and Ccr (r = 0.65, P < 0.01). These data indicate that patients with IgA nephropathy undergo glomerular hypertrophy subsequent to the reduction in nephron mass in the long‐term and glomerular hypertrophy may play an important role in the slow progression of patients with IgA nephropathy.
Pathogenesis and management of hyperparathyroidism in end‐stage renal disease and after renal transplantation
Authors: Elder Grahame J
Published: March 2003

SUMMARY:Secondary hyperparathyroidism is an adaptive response to progressive loss of renal function so as to maintain calcium and phosphate homeostasis, 1,25‐dihydroxyvitamin D3levels and normal bone turnover, despite skeletal resistance to parathyroid hormone. As feedback regulation fails, complications of parathyroid overactivity develop, and by the commencement of dialysis abnormal bone histology is present in almost all patients, with hyperparathyroid changes most commonly found. Post transplantation, persisting hyperparathyroidism predisposes to osteoporosis. The risk of bone disease is reduced by early, carefully targeted dietary measures and suppressive therapy with calcitriol and calcium‐based phosphate binders, while newer therapies include bisphosphonates and calcimimetics. Timely surgical intervention is necessary in some patients.
Role of interleukin‐10 in rat mesangioproliferative glomerulonephritis
Authors: ROBERTSON TARA E , NIKOLIC‐PATERSON DAVID J , TESCH GREG H , FOTI RITA , ATKINS ROBERT C , CHADBAN STEVEN J
Published: March 2003

SUMMARY: Interleukin‐10 (IL‐10) has been recognized as a growth factor for rat mesangial cells in vitro; however, its role in mesangioproliferative glomerulonephritis is unknown. We studied the expression of IL‐10 mRNA in the rat anti‐Thy‐1 model of mesangioproliferative glomerulonephritis (experiment 1) and, subsequently, the effects of blocking IL‐10 during anti‐Thy‐1 nephritis using the IL‐10 inhibitor, AS101 (experiment 2). In experiment 1, PCR analysis failed to detect IL‐10 mRNA in normal rat kidney, however, a clear signal for IL‐10 mRNA was evident on day 6 of anti‐Thy‐1 nephritis. In situ hybridization showed IL‐10 mRNA expression in focal glomerular areas in anti‐Thy‐1 nephritis. Combined in situ hybridization and immunohistochemistry showed that glomerular IL‐10 mRNA was expressed by both macrophages and mesangial cells. In experiment 2, treatment with AS101 significantly downregulated renal IL‐10 gene expression, as demonstrated by semiquantitative PCR. However, the induction of glomerular hypercellularity, mesangial proliferation (PCNA+ cells), mesangial cell activation (α‐SMA expression) and macrophage accumulation (ED1+ cells) seen in saline‐treated anti‐Thy‐1 nephritis was unaffected by AS101 treatment. In conclusion, renal IL‐10 gene expression is upregulated during pathological mesangial cell proliferation in rats with anti‐Thy‐1 nephritis. However, the inability of IL‐10 suppression with AS101 to prevent anti‐Thy‐1 disease suggests that IL‐10 is not essential for pathological mesangial cell proliferation.
Treatments conferring renoprotection in patients with Nephrotic Syndrome
Authors: Healy Helen
Published: March 2003

SUMMARY: Nephrotic Syndrome that fails to respond to specific treatment presents a major therapeutic conundrum. Management strategies aim to normalize glomerular filtration barrier dysfunction, optimize intrarenal haemodynamics to limit stress on capillary walls and limit adverse signalling profiles in the tubulo‐interstitial compartment. Angiotensin converting enzyme (ACE) inhibitors are currently the only proven therapeutic option for patients with Nephrotic Syndrome, although several other agents have demonstrated potential. However, these therapies have not been evaluated in well‐designed trials and their efficacy is largely untested. The angiotensin‐II receptor (AII) antagonists, that interrupt the renin‐angiotensin cascade at a different point to ACE inhibitors, may also have renoprotective effects although few long‐term data are available. The efficacy of another class of antihypertensive drugs, the calcium channel blockers, is unclear, perhaps because of the pharmacological heterogeneity among the group. Rigorous comparative studies of these different agents in patients with Nephrotic Syndrome have not been conducted. There are even less data about non‐antihypertensive agents like Cyclosporin A (CsA), dipyridamole and indomethacin. Dietary manipulations to restrict protein and sodium intake and reducing serum lipid levels with diet and drug intervention may have additional renal benefits in selected patients.
Treatment of IgA nephropathy in children
Authors: Yoshikawa Norishige
Published: March 2003

SUMMARY:
IgA nephropathy is the most common primary glomerulonephritis in the world, and about 20–50% of patients develop progressive renal failure. The pathogenesis is still unknown and treatment has not yet been established. Knowledge concerning childhood IgA nephropathy has expanded greatly in the last 10 years, and its importance as the major form of glomerulonephritis and major contributor to end‐stage renal disease is also becoming apparent in children. This communication focuses on the treatment of IgA nephropathy in children.