bluuebunny/crossref_metadata_2025 huggingface dataset:
Vector Transmission of Eggplant Mottled Dwarf Virus in Iran
Authors: Babaie Gh. , Izadpanah K.
Published: November 2003

Eggplant mottled dwarf virus (EMDV) is a plant rhabdovirus whose natural means of transmission has remained unknown. In the present study various arthropods including two mite, one psyllid, one thrips, five aphid, four planthopper and 14 leafhopper species were examined for their competence to vector EMDV. Healthy eggplant seedlings were inoculated by arthropods either from naturally infested EMDV infected plants or after having access to source plants and subsequent incubation on rearing host. Transmission was achieved only by the agallian leafhopper Agallia vorobjevi. Symptoms began to appear 20 days after inoculation. Viruliferous leafhoppers were also captured in the field. Symptomatic plants and vector leafhoppers reacted positively with EMDV antiserum in enzyme linked immunosorbent assay. This is the first report on the identification of EMDV vector in Iran.
A Study on Pathogenicity of Bacteria Carried by Pine Wood Nematodes
Authors: Han Z. M. , Hong Y. D. , Zhao B. G.
Published: November 2003

Three bacterial strains Njh, Njt and Njw, have been isolated with a high frequency from the xylem of the wilted black pine (Pinus thuntergii) and from the surface of the pine wood nematodes (Bursaphelenchus xylophilus). These bacteria have been identified as Pseudomonas fluorescens biotype I, P. fluorescens biotype II and a species of the genus Pantoea respectively. To determine pathogenicity, callus and aseptic black pine seedlings were inoculated as follows: aseptic nematodes only (each of B. xylophilus and B. mucronatus); bacterium only (each of bacterial strain Njh, Njt, Njw) and aseptic nematodes plus bacterium (each of B. xylophilus and B. mucronatus in combination with each of Njh, Njt, Njw). The results showed that inoculation with either aseptic B. xylophilus or B. mucronatus did not lead to browning of the callus or wilt of aseptic black pine seedlings. But those inoculated with aseptic nematodes plus any one of Njh, Njt, Njw showed some wilting or browning symptoms. The combination of nematodes plus either Njh or Njt caused severe symptoms but the combination of nematodes plus Njw had fewer symptoms. The bacteria carried by pine wood nematodes played an important role in pathogenicity. In addition, bacteria were cultured in liquid media through shaking. The filtered liquid was directly applied to the callus and the ability of each kind of bacterium to induce browning was determined. The results showed that Njh and Njt caused severe browning but Njw did not. It is suspected that this is due to wilt related toxins in the bacterial culture fluid. Therefore, it's suggested that the disease was caused by co‐infection of both pine wood nematodes and bacteria and possible toxic effect of bacteria.
Relationship between Management Practices, Fungal Infection and Aflatoxin for Stored Maize in Benin
Authors: Hell K. , Cardwell K. F. , Poehling H.‐M.
Published: November 2003

This study relates preharvest and harvest practises to postharvest quality of maize in Benin, West Africa. Fungal infection and aflatoxin levels were evaluated in 300 farmers’ stores in four agro‐ecological zones over 2 years (1993–1995), at the beginning of storage (sample A) and 6 months later (sample B). Aspergillus flavus infected 10–20% of the kernels in sample A (1993–1994). In sample B, 54–79% of the kernels were infected with A. flavus. In 1994–1995, A. flavus infection was higher in sample A (27–47%) than B (8–26%). Fusarium species were found in 38–58% of the kernels in sample A in both years, but decreased slightly to 29–51% in sample B. Significant agroecozonal effects existed within sampling, but were not consistent between samplings and years. Of the total number of samples collected (744), 38.8% were found to be aflatoxin‐positive, with an average of 105 parts per billion (ppb) and 60% of the aflatoxin‐positive samples having a contamination approximately 20 ppb, the intervention level recommended by the World Health Organization. Factors associated with increased aflatoxin were: planting local maize varieties in southern Benin, intercropping with cowpea, groundnut, or cassava, use of urea‐fertilizer, damage to maize in the field, prolonged harvesting, long drying periods in the field, and winnowing. Practices that reduced aflatoxin contamination were: planting improved varieties in northern Benin, mixed cropping with vegetables, use of NPK‐fertilizer, drying of harvested cobs for 60–90 days, drying ears without the husk, sorting out of poor quality ears.
Extracerebral ectopic mass with huge cysts in the anterior cranial cavity
Authors: Toyoshima Yasuko , Kakita Akiyoshi , Yamada Mitsunori , Sato Gen , Mori Hiroshi , Okamoto Kouichirou , Tanaka Ryuichi , Takahashi Hitoshi
Published: November 2003

In the present study, an unusual example of malformation in a 9‐day‐old‐girl, in whom an extracerebral ectopic mass with cysts was found in the anterior cranial cavity, is reported. The brain proper was well developed. The mass was connected to the cerebral base and consisted of neuroglial tissue showing various characteristics of differentiation, including cerebellar cortex and monoaminergic neurons. The ectopia may have developed from the medio‐basal portion of the embryonic telencephalon.
Widespread vertebral and epidural venous plexus metastasis of prostatic carcinoma presenting wedge‐shaped radial lesions in the spinal cord
Authors: Oyanagi Kiyomitsu , Ogata Kentaro , Takeda Shigeki , Horikawa Yo , Kawakami Emiko , Morita Takashi
Published: November 2003

The present case is the first autopsy case of prostatic carcinoma presenting widespread spinal epidural venous plexus tumor cell emboli with wedge‐shaped spinal cord lesions. There has been no previous report of prostatic carcinoma showing tumor cell emboli in the spinal and cranial base epidural venous plexus, in spite of the fact that the incidence of vertebral metastasis in prostatic carcinoma is high, and that presence of continuity from pelvic organs to venous plexus around vertebrae, up to foramen magnum, has been reported. The present case shows that the possibility of spinal cord injury, not by direct compression, but by venous circulatory disturbance as a result of tumor cell emboli to veins, should be taken into consideration on medical treatment of prostatic carcinoma.
Morphological changes and stress responses in neurons in cerebral cortex infiltrated by diffuse astrocytoma
Authors: Goel Shom , Wharton Stephen B. , Brett Laurence P. , Whittle Ian R.
Published: November 2003

Local dysfunction in cerebral cortex infiltrated by astrocytoma can cause epilepsy and focal neurological deficits, but the cellular pathology of peritumoral cortex remains poorly defined. The aims of the present study were to define the morphological changes which occur in neurons in tumor‐infiltrated cerebral cortex, and to determine whether peritumoral neurons show expression of cell stress‐related proteins. Archival specimens of diffuse astrocytoma (n = 28) were identified with areas of both tumor‐infiltrated cortex and apparently non‐infiltrated cortex. Immunohistochemistry was performed to structural neuronal proteins (MAP‐2, neurofilament proteins), β‐amyloid precursor protein, growth associated protein‐43 and to injury response proteins (poly(ADP‐ribose) polymerase, poly(ADP‐ribose), c‐fos, and c‐jun). Tumor‐infiltrated cortex revealed neuronal loss and architectural disarray compared to non‐infiltrated cortex. Pyramidal neurons showed thinning of the cytoplasmic rim and their neuritic processes showed increasing tortuosity, varicosity, fragmentation and loss, with axonal spheroid formation and dendritic beading. Poly(ADP‐ribose) polymerase, poly(ADP‐ribose) and c‐fos were up‐regulated in both infiltrated and non‐infiltrated cortex, but c‐jun expression was greater in areas of tumor‐infiltrated cortex. Surviving neurons in cortex infiltrated by astrocytoma demonstrate, therefore, a sequence of morphological alterations in their dendritic, somatic and axonal compartments, and demonstrate a cell stress response. The patterns of cellular pathology identified suggest possible mechanisms, by which neurons are damaged and eventually lost in peritumoral brain.
Cytokeratin 7 and 20 as immunohistochemical markers in identification of primary tumors in craniospinal metastases: Do they have a significant role?
Authors: Taweevisit Mana , Isarakul Putchong , Chaipipat Mookda , Keetacheeva Kanista , Wattanasirmkit Vannee , Shuangshoti Shanop
Published: November 2003

Cytokeratin (CK)7 and CK20, the low molecular weight cytokeratins, have been found to have a benefit in the differential diagnosis of some epithelial neoplasms. In the present study, the actual role of these markers in the search of primary tumors in 32 patients with craniospinal metastasis of an unknown primary site at presentation, is evaluated. A series of 36 patients with a known primary tumor were presented for comparison. In the first group, two CK7 and CK20 expression profiles were observed; 87% of metastatic tumors were CK7+/CK20‐ and 13% CK7‐/CK20‐. The lung was the major source (82%) of CK7+/CK20‐ metastatic tumors, whereas it represented only 38% of primary tumor in the second group of a known primary site (P = 0.006). Given the fact that metastatic tumors to the craniospinal axis of an unknown primary site are frequently CK7+/CK20‐, and they have commonly metastasized from the lung, it is doubtful that immunohistochemistry is really helpful. However, CT scan and MRI of the chest still play an important role. Many patients in the present study had to undertake these imaging studies, regardless of the CK7/CK20 result. The immunostains may be useful in cases with other expression profiles, but such examples constituted only a minority in the present study.
Two distinct subgroups of senile dementia of Alzheimer type: Quantitative study of neurofibrillary tangles
Authors: Mizuno Yutaka , Ikeda Kenji , Tsuchiya Kuniaki , Ishihara Ryoko , Shibayama Hiroto
Published: November 2003

The heterogeneity of senile dementia of Alzheimer type (SDAT) has been suggested by some authors clinically and neuropathologically. The heterogeneity of SDAT was investigated based on quantification of NFT combining Braak and Braak's neuropathological staging and the density of NFT in various areas of the cerebral cortex. Brain tissues were examined from 16 autopsy cases with clinically late onset dementia (>age 65) and neuropathologically diagnosed dementia of Alzheimer type (DAT). Gallyas–Braak staining was used for the quantification of NFT. The density of NFT was examined in the precentral gyrus, middle temporal gyrus (T2), parahippocampal gyrus and the amygdaloid nucleus. The 16 cases studied were divided into two groups depending on the number of NFT in the cortex (cut–off score: 5/mm2): the AD‐like group (NFT ≥ 5/mm2) and the common group (NFT < 5/mm2). The density of NFT in the precentral gyrus (t(3.225) = −9.007, P = 0.002) and T2 (t(3.365) = −3.774, P = 0.027) in the AD‐like group was significantly higher than those in the common group. However, no significant difference was observed in the parahippocampal gyrus between the two groups (t(14) = −0.318, NS). Moreover, there were no significant differences between the two groups as regards age at onset and the duration of the illness. The present study revealed the possible existence of two subgroups in SDAT having significantly different NFT densities in various areas of the cerebral cortex without any significant difference in their duration of illness. This classification has no relationship to Braak and Braak's staging, which depends only on the distribution of NFT, irrespective of their density. Arai et al. revealed that the NFT density in AD was significantly higher than in SDAT. We suggest that the neuropathological findings of the AD‐like group in SDAT resemble those of presenile AD.
Cerebral arterial pathology of CADASIL and CARASIL (Maeda syndrome)
Authors: Arima Kunimasa , Yanagawa Sohei , Ito Nobuo , Ikeda Shu‐ichi
Published: November 2003

Two familial cerebro‐vascular diseases characterized by different cerebral arterial pathologies and presenting in non‐hypertensive young and middle‐aged adults are described. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by the deposition of smudged periodic acid–Schiff (PAS)‐positive granules known as granular osmiophilic materials (GOM) in the media of small arteries and arterioles. The medial smooth muscle cells are completely lost, and intense adventitial fibrosis is present. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), or Maeda syndrome, is characterized by intense arteriolosclerosis without GOM deposition. Fibrous intimal proliferation, hyaline degeneration of the media, thickening and splitting of the internal elastic lamina, and concentric narrowing of the lumen are characteristic features. In PAS preparation, small arteries are occasionally stained homogeneously due to exudative changes, but never exhibit granular appearance in CARASIL (Maeda syndrome). Each of the small arterial changes is intense in the cerebral medullary and leptomeningeal arteries, leading to multifocal, confluent, or diffuse ischemic changes in the cerebrum. The authors suggest that CARASIL be referred to as ‘Maeda syndrome’ or ‘CARASIL (Maeda syndrome)’ to avoid confusion with CADASIL.
Idiopathic hypertrophic pachymeningitis
Authors: Riku Shigeo , Kato Shigenori
Published: November 2003

Idiopathic hypertrophic pachymeningitis is a rare disorder of unknown origin. It is a fibrosing inflammatory process that involves the dura mater. Herein are described 14 patients with idiopathic hypertrophic pachymeningitis; their clinical, laboratory and radiological findings, as well as their treatment, are analyzed. Neuropathological findings of six cases including two autopsied cases are also presented. The main clinical features were headache and cranial nerve palsies. Many patients had mild to moderate elevation of C‐reactive protein, and three patients had perinuclear antineutrophil cytoplasmic antibody. The CSF in most cases showed inflammatory changes. Neuroimaging studies revealed diffuse or localized thickening of the dura, and MRI findings were key to diagnosis of this disorder. The clinical course was chronic. All patients were treated with corticosteroid and improved intially, but half of them experienced relapses. Two patients received surgical intervention. Pathological examination in two autopsied cases revealed diffuse thickening of the dura, especially in the posterior part of the falx cerebri and the tentorium cerebelli. Microscopic examination of the dura showed dense fibrosis with inflammatory cell infiltration composed mainly of lymphocytes. The cell infiltration was marked at the surface of the dura mater. One case had necrotizing vasculitis of the small arteries located in the dura and the cerebral surface. There were no giant cells, caseation necrosis, or epitheloid granuloma. Four patients underwent biopsy of the dura, and the pathological study showed non‐specific inflammatory changes. The relationship of idiopathic hypertrophic pachymeningitis with connective tissue disease or vasculitis syndrome is discussed.
Aceruloplasminemia, an iron metabolic disorder
Authors: Miyajima Hiroaki
Published: November 2003

Aceruloplasminemia is an inherited disorder of iron metabolism caused by the complete lack of ceruloplasmin ferroxidase activity caused by mutations in the ceruloplasmin gene. It is characterized by iron accumulation in the brain as well as visceral organs. Clinically, the disease consists of the triad of adult‐onset neurologic disease, retinal degeneration and diabetes mellitus. The neurological symptoms, which include involuntary movements, ataxia, and dementia, reflect the sites of iron deposition. Severe iron overload and extensive neuronal loss were observed in the basal ganglia, while iron deposition and neuronal cell loss were trivial in the frontal cortices. The cerebellar cortex showed marked loss of Purkinje cells. Iron deposition was more prominent in the astrocytes than in the neurons. Excess iron functions as a potent catalyst of biologic oxidation. Astrocytic deformity and globular structures are characteristic features in aceruloplasminemia brains. The globular structures in the astrocytes were seen in proportion to the degree of iron deposition and reacted positively to anti‐4‐hydroxynonenal, one of the indicators of lipid peroxidation,  and  anti‐ubiquitin  antibodies,  but  not to  anti‐α‐synuclein antibody. The lack of ceruloplasmin may primarily damage astrocytes in the aceruloplasminemia brains through lipid peroxidation. Ceruloplasmin may play an essential role in neuronal survival in the central nervous system.
Senile dementia of the neurofibrillary tangle type (tangle‐only dementia): Neuropathological criteria and clinical guidelines for diagnosis*
Authors: Yamada Masahito
Published: November 2003

Senile dementia of the NFT type (SD‐NFT) is a subset of dementia in the elderly, characterized by numerous NFT in the hippocampal region and absence or scarcity of senile plaques throughout the brain. Senile dementia‐NFT has also been referred to as tangle‐only dementia, NFT‐predominant form of SD, SD with tangles, or limbic NFT dementia. Herein are proposed the criteria for neuropathological diagnosis of SD‐NFT: (i) late‐onset dementia with abundant NFT in the hippocampal region and absence or scarcity of senile plaques (amyloid β protein deposits) throughout the brain; and (ii) exclusion of other dementias with NFT. Some elderly individuals suffering from memory disorder without obvious dementia have neuropathological findings similar to SD‐NFT, and they would represent a condition in the process of formation of the SD‐NFT pathology. Guidelines for the clinical diagnosis of SD‐NFT are also proposed; development of reliable diagnostic tests is necessary to differentiate AD and other neurodegenerative dementias from SD‐NFT.
Neuronal intranuclear hyaline inclusion disease
Authors: Takahashi‐Fujigasaki Junko
Published: November 2003

Neuronal intranuclear hyaline inclusion disease (NIHID) is a rare neurodegenerative disorder characterized pathologically by the presence of eosinophilic intranuclear inclusions in neuronal and glial cells. It has been considered to be a heterogeneous disease entity because the clinical pictures of previously described cases were highly variable. In the present review, reported NIHID cases have been categorized into three clinical subgroups according to onset and disease duration, and the clinical phenotype of each subgroup is discussed. Neuronal intranuclear inclusions (NII) in NIHID are ubiquitinated and their prevalence is inversely correlated with neuronal loss, suggesting that NII formation is a protective mechanism involving the ubiquitin–proteasome‐dependent proteolytic pathway. In several polyglutamine diseases, disease‐related proteins containing abnormally expanded polyglutamine tracts aggregate in neuronal nuclei, resulting in NII formation. The similarity between NII in NIHID and polyglutamine diseases suggests that they are formed during a common proteolysis‐related process that takes place in the nucleus. Although the pathogenetic mechanism underlying NIHID remains unknown, the data reviewed here suggest that it might be related to accumulation of as yet unidentified abnormal proteins or dysfunction of the intranuclear ubiquitin–proteasome pathway.
Analysis of Ki‐ras and p53 gene mutations in laterally spreading tumors of the colorectum
Authors: Noro Akihiro , Sugai Tamotsu , Habano Wataru , Nakamura Shin‐ichi
Published: November 2003

A laterally spreading tumor (LST) is considered to be a specific subtype of superficial colorectal tumors, in view of its characteristic clinicopathological features. We attempted to compare genetic alterations found in LST (>10 mm) with those found in IIa‐type adenomas (10 mm or less (small superficial elevated lesion)) and conventional polypoid adenomas (>10 mm). In addition, multiple sampling by microdissection was performed for 14 LST to examine genetic heterogeneity in the Ki‐ras and p53 gene mutation patterns. Polymerase chain reaction, single‐strand conformation polymorphism and direct sequencing were used to analyze Ki‐ras and p53 gene mutations in 73 sporadic colorectal adenomas: 28 LST; 22 IIa‐type adenomas; and 23 polypoid adenomas. Ki‐ras gene mutations were found more frequently in LST (6/28 tumors) and polypoid adenomas (6/23 tumors) than in IIa‐type adenomas (2/22 tumors), although this difference was not statistically significant. The frequency of p53 gene mutations in the 28 LST was 25% (7/28), which was significantly higher than that found in IIa‐type adenomas (P < 0.05). However, although p53 gene mutations were found more frequently in LST than in polypoid adenomas, this difference was not statistically significant. Seven LST exhibited a combination of wild‐type and mutant‐type tumor cells having the p53 gene mutation pattern, whereas a pattern of different Ki‐ras gene mutations was found in two of three LST that exhibited Ki‐ras gene mutation heterogeneity. We suggest that the LST exhibited a characteristic pattern in terms of the Ki‐ras as well as the p53 gene mutation pattern, thereby supporting the hypothesis that LST is a specific subtype of colorectal tumors.
Significance of hormone receptor status and tumor vessels in normal, hyperplastic and neoplastic endometrium
Authors: Nunobiki Osamu , Taniguchi Emiko , Ishii Aiko , Tang Weihua , Utsunomiya Hitoshi , Nakamura Yasushi , Mori Ichiro , Kakudo Kennichi
Published: November 2003

The aims of this study were to identity the roles of tumor vessels and hormone receptor status in normal, hyperplastic, and neoplastic endometrium, and to explore their relationships with other prognostic factors of endometrial adenocarcinoma. Endometrial curettage specimens of proliferative phase and secretory phase endometrium, simple hyperplasia with or without atypia, complex hyperplasia with or without atypia, and grade 1 adenocarcinoma were examined for estrogen receptor alpha (ER alpha), progesterone receptor (PgR), Ki‐67 labeling index (LI), cyclin D1, microvessel density (MVD), and area of venules (AV) using an immunoperoxidase method. The results showed high levels of ER alpha in complex hyperplasia, and high levels of PgR in simple hyperplasia without atypia. Expression of ER alpha in the endometrium decreased in a stepwise manner from complex hyperplasia without atypia to grade 1 adenocarcinoma. Expression of PgR in the endometrium decreased in a stepwise manner from simple hyperplasia without atypia to grade 1 adenocarcinoma. In contrast, the expressions of Ki‐67 LI, cyclin D1, MVD and AV in the endometrium increased in a stepwise manner from normal, simple or complex hyperplasia with or without atypia to grade 1 adenocarcinoma. These changes may become irreversible on progression from simple or complex hyperplasia to neoplasia.
Expression of CD34 antigen in testicular mixed germ cell tumor
Authors: Hamazaki Shuji , Okada Shigeru
Published: November 2003

The expression of CD34 was investigated in 14 cases of testicular mixed germ cell tumor to elucidate the relationship between its expression and histological patterns. Seven of 12 yolk sac tumor components were focally immunoreactive for anti‐CD34 antibody. Of these, five showed focal but intense CD34 staining, while the remaining two tumors showed weak staining in small clusters or isolated tumor cells. Positive immunostaining for CD34 was seen predominantly in solid and reticular patterns of the yolk sac tumor components. Seminoma, embryonal carcinoma, and choriocarcinoma components were invariably negative for CD34. If present, immunoreactivity for CD34 in yolk sac tumors is focal and variable, but useful for the distinction from other germ cell tumors.
Small cell carcinoma of the prostate expressing prostate‐specific antigen and showing syndrome of inappropriate secretion of antidiuretic hormone: An autopsy case report
Authors: Kawai Shigeo , Hiroshima Kenzo , Tsukamoto Yoshiaki , Tobe Toyofusa , Suzuki Hiroyoshi , Ito Haruo , Ohwada Hidemi , Ito Hisao
Published: November 2003

An autopsy case of primary small cell carcinoma (SCC) of the prostate in a 68‐year‐old man is reported. The patient was admitted to hospital because of a bloody stool and suspected rectal cancer. However, a diagnosis of prostate cancer was made on the basis of a digital rectal examination, the serum level of prostate‐specific antigen, and a needle biopsy of the prostate. The patient also experienced a syndrome of inappropriate secretion of antidiuretic hormone. He died 29 days after admission. At autopsy, the tumor had invaded the rectum, bladder and pelvic peritoneum. Metastases to the heart, vertebrae and lymph nodes were observed. Microscopically, the tumor was composed of small round cells that showed a solid growth pattern. Rosette formations were observed. Immunohistochemically, the tumor cells were positive for a prostatic epithelial marker and neuroendocrine markers. A high level of antidiuretic hormone was detected in the tumor tissue. To our knowledge, this is the first reported case of SCC of the prostate in which both a prostatic epithelial marker and neuroendocrine markers have been found in the same tumor. This finding supports the hypothesis that SCC of the prostate originates from a multipotential stem cell of the prostatic epithelium.
Lung adenocarcinoma associated with atypical adenomatous hyperplasia. A clinicopathological study with special reference to smoking and cancer multiplicity
Authors: Kitagawa Hiroshi , Goto Akiteru , Niki Toshiro , Hironaka Mitsugu , Nakajima Jun , Fukayama Masashi
Published: November 2003

Atypical adenomatous hyperplasia (AAH) of the lung has been proposed as a possible precursor lesion of adenocarcinoma of the lung. In the present study, we sought to clarify the clinicopathological characteristics of lung adenocarcinoma cases associated with AAH, with special reference to tobacco smoking and the presence of multiple primary carcinomas of pulmonary and extrapulmonary organs. We examined 123 surgically resected lung adenocarcinomas and conducted histopathological diagnoses for AAH and multiple primary pulmonary carcinomas. Clinicopathological characteristics such as age, sex, smoking index, survival, and the presence of extrapulmonary primary carcinomas were obtained from clinical records, and the associations among these factors were examined statistically. Sixteen lung adenocarcinoma patients had accompanying AAH (the AAH group) and 107 cases did not (the NAAH group). The incidence of primary carcinomas in extrapulmonary organs was higher in the AAH group (37.5%; 6/16) than in the NAAH group (12.5%; 13/107) (P = 0.01). Multiple primary lung cancers tended to be more frequent in the AAH group, but the difference was not statistically significant (P = 0.07). Although there was no difference in tobacco smoking between the two groups, all eight cases with multiple primary lung carcinomas were smokers. Furthermore, multiple primary lung carcinomas were found more frequently in smokers of the AAH group (37.5%; 3/8) than in the smokers of the NAAH group (7.2%; 5/69) (P = 0.04). The results suggested that constitutional or genetic factors might predispose patients to the development of AAH together with extrapulmonary primary carcinomas, and that smoking might contribute to the development of multiple primary lung adenocarcinomas, especially in patients with pre‐existing AAH.
Microwave cell death: Enzyme histochemical evaluation for metastatic carcinoma of the liver
Authors: Ozaki Takashi , Tabuse Katsuyoshi , Tsuji Takeshi , Nakamura Yasushi , Kakudo Kennichi , Mori Ichiro
Published: November 2003

We have reported that microwave cell death is a unique cell death preserving not only cell and nuclear shapes but also immunohistochemical antigenicity. However, their enzyme activity was lost, which indicated cell dysfunction and death. This peculiar observation implies that the microwave effect is likely an ‘in situ’ tissue fixation and that this type of cell death is morphologically different from cell death, by either oncosis or apoptosis, as previously known. To confirm whether this peculiar cell death was observed also in human tissue samples, we examined clinical samples from patients with metastatic liver cancer, which were treated with microwave irradiation. They were examined immunohistochemically for human Ki‐67 antigen and proliferating cell nuclear antigen and enzyme histochemically for alkaline phosphatase, and the same morphological changes that were observed in microwave‐treated rat liver were found. In conclusion, we believe that routine hematoxylin‐eosin stain alone is not a suitable method to evaluate microwave treatment for cancer because microwave coagulation therapy‐treated cells preserved their nuclei and cellular architectures, even after 3 months. For microwave‐treated tumors, enzyme histochemistry is helpful to determine its effectiveness.
Glioblastomatous transformation of ganglioglioma: Case report with reference to molecular genetic and flow cytometric analysis
Authors: Kim Na Rae , Wang Kyu‐Chang , Bang Jae‐Seung , Choe Gheeyoung , Park Young , Kim Seung‐Ki , Cho Byung‐Kyu , Chi Je G.
Published: November 2003

Gangliogliomas generally behave as benign indolent tumors. However, gangliogliomas undergoing malignant transformation have also been reported. The molecular basis for the malignant transformation of gangliogliomas remains unclear. We describe a case of ganglioglioma, which had transformed to glioblastoma after the gross total resection of the original tumor, in a 4‐year‐old girl. The present case is unusual in four aspects: (i) it arose from a low‐grade ganglioglioma in the absence of previous radiation or chemotherapy, which is the fourth reported case; (ii) the original tumor showed a high proliferative index on flow cytometry but a low Ki‐67 labeling index, implying that the application of flow cytometry might play a certain role in predicting biological and clinical behavior of low grade gangliogliomas; (iii) p53 mutation and deletion appeared in the secondary glioblastoma, which was not shown in the original well‐differentiated ganglioglioma; and (iv) the transformed glioblastoma showed p16 inactivation detected by methylation and deletion, which are relatively uncommon genetic events in secondary glioblastomas. This is the first report of a genetic alteration in glioblastoma arising from a well differentiated ganglioglioma prior to radiation or chemotherapy. Based on the above findings, irrespective of radiotherapy or chemotherapy, rare recurrence of malignant evolution, especially tumors of high S‐phase fraction on flow cytometry, warrants long‐term follow‐up, even in a well‐differentiated ganglioglioma.
Long‐term efficacy of mycophenolate mofetil in the control of severe intraocular inflammation
Authors: Lau Chun H , Comer Marie , Lightman Susan
Published: November 2003

Purpose: To assess whether the previously demonstrated short‐term efficacy of the immunosuppressant mycophenolate mofetil (MMF; CellCept, Roche) is maintained in the long‐term management of refractory uveitis.

Methods: The study was an open‐label, non‐comparative retrospective series of 14 patients with refractory uveitis and treated with MMF for a mean of>33 months. Mycophenolate mofetil was given at a dosage of 1 g (oral) twice daily. Indications included prednisolone reduction, additive agent with cyclosporin, or replacement therapy (azathioprine or methotrexate). The intraocular inflammatory response, side‐effects, and toxicity were monitored.

Results: Intraocular inflammation remained under control in 10 patients, unchanged in three and deteriorated in one patient. Transient side‐effects included tiredness, headache and dizziness (one patient each, lasting less than 2 weeks from the time of MMF introduction). Mycophenolate mofetil was stopped in one patient because of absence of prolonged clinical improvement. Vision improved in 25% (7 eyes), did not change in 50% (14 eyes), but was reduced in 25% (7 eyes).

Conclusions: Mycophenolate mofetil is safe for long‐term usage and is recommended for treatment of refractory panuveitis or posterior uveitis with uncontrolled inflammation despite high prednisolone maintenance dosage (>15 mg/day) or toxicity or lack of efficacy of other immuno­suppressive agents. However, MMF is less effective for refractory uveitis unresponsive to azathioprine.
In vivo effects of fluoroquinolones on rabbit corneas
Authors: Pollock Graeme A , McKelvie Penelope A , McCarty Daniel J , White Jacinta F , Mallari Peter LT , Taylor Hugh R
Published: November 2003

Purpose: The use of topical fluoroquinolones to treat microbial keratitis is associated with an increased incidence of corneal perforation compared to other standard treatments. This study examined the effects of topical fluoro­quinolones on corneal collagen and keratocytes in intact rabbit corneas and corneas with an epithelial defect.

Methods: Studies consisted of one group of intact corneas and one group of corneas where a 6‐mm epithelial defect was created with a surgical scrape. Within each group, eyes were randomly assigned to one of four topical medications (0.3% ciprofloxacin, 0.3% ofloxacin, fortified antibiotics (1.36% tobramycin, 5% cefrazolin) or Tears Naturale (Alcon Laboratories, Frenchs Forest, NSW, Australia). Two drops were instilled hourly for 48 h and then 2‐hourly for an additional 48 h. At 96 h the corneas were removed and processed for light microscopy, immunohistology for collagen IV, V and VI, and apoptosis staining.

Results: In intact rabbit corneas there was no demonstrable difference between treatment groups. In corneas with an epithelial defect, both fluoroquinolones delayed epithelial healing when compared to fortified antibiotics or tears. Keratocyte loss was seen in all groups and was greatest in the ofloxacin group. Median stromal thickness with keratocyte loss were: ofloxacin 30%; ciprofloxacin 10%; fortified antibiotics 7.5%; and tears 15% (ofloxacin vs tears, Mann−Whitney = 16.0, P = 0.09). Keratocyte loss did not correlate with the amount of demonstrable apoptosis. Collagens IV, V and VI showed no differences between treatments.

Conclusions: These results suggest that ofloxacin is potentially cytotoxic to corneal keratocytes. Such an effect could lead to the observed increased incidence of corneal per­foration in microbial keratitis.
Serum melatonin levels following enucleation and transpupillary thermotherapy in patients with choroidal melanoma
Authors: Kiratli Hayyam , Gedik Sansal , Us Dürdal , Bilgiç Sevgül
Published: November 2003

Purpose: To study serum melatonin levels in patients with choroidal melanoma preoperatively and following enucleation and transpupillary thermotherapy.

Methods: Forty patients with preoperative choroidal melanoma were included in the study. Of these, 15 patients underwent enucleation (group 1) and 25 patients received transpupillary thermotherapy (group 2). A further 20 patients without melanoma acted as age‐matched controls. Serum melatonin levels were determined 1 day preoperatively, and at the first and sixth months postoperatively using ELISA.

Results: Preoperative serum melatonin levels were highest in group 2 followed by group 1, but this was not statistically significant compared to controls. Postoperatively, a constant decrease of serum melatonin was observed in both groups after the first month, which reached statistical significance at the sixth month (P = 0.003). Also, a significant regression in tumour thickness was documented in group 2 (P = 0.003). Three patients in group 1 developed hepatic metastases.

Conclusions: Patients with choroidal melanomas had higher levels of serum melatonin compared to individuals without tumours. Smaller tumours were associated with more elevated melatonin levels compared to larger tumours. Serum melatonin levels fell considerably following enucleation and transpupillary thermotherapy.
Corneal endothelial status in the subtypes of primary angle closure glaucoma
Authors: Sihota Ramanjit , Lakshmaiah N Chinna , Titiyal Jawahar S , Dada Tanuj , Agarwal Harish C
Published: November 2003

Purpose: To study the corneal endothelium and pachy­metry in eyes with different subtypes of primary angle closure glaucoma (PACG), as compared to controls.

Methods: A cross‐sectional study was conducted on 30 consecutive patients in each subtype of PACG, subacute, acute and chronic, and 30 age and refraction matched controls. The parameters recorded included gonioscopy, optic disc evaluation, applanation tonometry, specular microscopy and central ultrasonic pachymetry.

Results: The mean endothelial cell counts in the four groups were as follows: subacute PACG 2396 ± 271 cells/mm2, acute PACG 1597 ± 653 cells/mm2, chronic PACG 2229 ± 655 cells/mm2 and controls 2461 ± 321 cells/mm2. The mean endothelial cell count in the fellow eyes of subacute PACG, acute PACG and chronic PACG patients was 2294 ± 305 cells/mm2, 2388 ± 226 cells/mm2 and 2108 ± 203 cells/mm2, respectively (NS). The acute PACG patients had significantly lower endothelial cell counts (P < 0.001) as compared to the other three groups. Eyes in which the acute attack of angle closure persisted for less than 72 h had a mean endothelial cell count of 2016 ± 306 cells/mm2, as compared to 759 ± 94.4 cells/mm2 in eyes with an attack lasting for 72 h or more (P < 0.001). The endothelial count was also significantly lower in eyes with chronic PACG as compared to control eyes (P < 0.001). There was increased pleomorphism and polymegathism of the corneal endothelial cells seen in eyes with resolved acute and chronic PACG. The mean central corneal thickness was 531.4 ± 25.3 µm in eyes with subacute PACG, 567.9 ± 37.3 µm in eyes with acute PACG, 526.4 ± 31.9 µm in eyes with chronic PACG and 525 ± 12.6 µm in control eyes. The acute PACG eyes had a significantly higher corneal thickness (P < 0.001) when compared to all the other groups.

Conclusion: There is a significant decrease in the corneal endothelial cell density in eyes that have had an acute attack of angle closure glaucoma and in eyes with chronic PACG. The endothelial cell population in eyes with sub­acute PACG and in the fellow eyes of all subtypes of PACG is not significantly different from the normal population.
Iris colour, ethnic origin and progression of age‐related macular degeneration
Authors: Nicolas Caroline M , Robman Luba D , Tikellis Gabriella , Dimitrov Peter N , Dowrick Adam , Guymer Robyn H , McCarty Catherine A
Published: November 2003

Aim: To investigate the relationship between iris colour, ethnic origin and the progression of age‐related macular degeneration (AMD).

Methods: Participants were recruited from the population‐based Melbourne Visual Impairment Project or the prospective, randomized, double‐masked Vitamin E, Cataract and Age‐Related Macular Degeneration study. From these two cohorts, 171 participants aged between 52 and 93 years who were identified as having early AMD features at their baseline examination (1992−1995) were followed for an average of 6.8 years (until 2001) to determine the progression rate of early AMD. The participants’ iris colour was categorized as light, intermediate or dark. Ethnic origin was categorized as Anglo‐Saxon or non‐Anglo‐Saxon, according to the participants’ grandparents’ country of birth.

Results: In total, 53 (31%) of the 171 participants showed signs of AMD progression. Participants with light iris colour had twofold the risk of AMD progression of those with dark or intermediate iris colours, although the age‐adjusted and multivariate‐adjusted associations were not significant (both P = 0.13). Age‐adjusted and multivariate comparisons of Anglo‐Saxon ethnic origin to non‐Anglo‐Saxon ethnic origin showed a noticeable but non‐significant association with progression of AMD (P= 0.22 and P= 0.14, respectively).

Conclusion: Individuals with light iris colour or of Anglo‐Saxon ethnic origin had a strong tendency to greater progression of AMD. A larger sample is required to confirm these clinically important, but statistically non‐significant, associations.
Associations between glaucomatous visual field loss and participation in activities of daily living
Authors: Noe Geertje , Ferraro John , Lamoureux Ecosse , Rait Julian , Keeffe Jill E
Published: November 2003

Purpose: This study investigated the association between visual field loss and participation in daily activities in individuals with glaucoma.

Methods: Seventy‐nine patients were recruited from the Royal Victorian Eye and Ear Hospital. Visual fields were assessed using the Esterman binocular visual field tests and participation in daily activities was assessed using the Impact of Vision Impairment (IVI) questionnaire. Visual acuity and contrast sensitivity were also measured.

Results: There was no independent relationship between visual field loss and IVI score (r = −0.20; P = 0.09), except for the mobility domain (r = 0.25; P = 0.03). Mobility was the most affected domain of the IVI (mean = 1.2). Over a quarter of the patients reported experiencing moderate to severe restriction with mobility activities despite relatively minor binocular field loss.

Conclusion: Mobility is the area in which glaucoma patients encounter difficulties even when the visual field and visual acuity are relatively good. Questions related to mobility could be asked to identify those patients who need rehabilitation.
Three horizontal muscle squint surgery for large angle infantile esotropia
Authors: Forrest Michael P , Finnigan Sidney , Finnigan Sonya , Gole Glen A
Published: November 2003

Background: To report the long‐term outcome of a series of 49 patients who underwent three horizontal muscle squint surgery for large angle infantile esotropia.

Methods: The patient records were retrospectively reviewed of 49 (24 girls [49%], 25 boys) consecutive patients with infantile esotropia of angle ≥60 Δ, who had undergone three horizontal muscle surgery performed by one surgeon (author GG). Surgery consisted of bilateral medial rectus recession combined with graded unilateral lateral rectus resection. Surgeries were carried out over a 6‐year period with a mean follow‐up period of 32.9 months (3.7−71.8 months).

Results: Using Kaplan−Meier life‐table analysis, cumulative surgical success (orthotropia ±10 Δ) was 93.9% at 1 week, 91.8% at 2 and 6 months, 87.7% at 12 and 18 months, 79.9% at 2 years, 77.1% at 3, 4 and 5 years, and 70.6% at 6 years. The mean preoperative deviation was 68.7 Δ. The mean age at surgery was 12.9 months. The failure rate was independent of preoperative deviation. Prevalence of residual esotropia (>10 Δ) varied from 2.0% at 1 week to 17.0% at 6 years. Similarly the prevalence of consecutive exotropia (>10 Δ) varied from 4.0% at 1 week to 12.4% at 6 years.

Conclusion: Operating in a graded fashion on three horizontal muscles in children with large angle infantile esotropia has a high success rate, even over long‐term follow up. Based on the study's results, amounts of surgery for a given angle of strabismus are proposed.
Photodynamic therapy in practice: a review of the results of the first 12 months experience with verteporfin at the Royal Victorian Eye and Ear Hospital
Authors: Essex Rohan W , Qureshi Salmaan H , Cain Melinda S , Harper C Alex , Guymer Robyn H
Published: November 2003

Purpose: To review the 12‐month results of the first 136 eyes treated with photodynamic therapy (PDT) with verteporfin at a single institution, and to determine if this treatment when used in the broader community could reproduce the results achieved in the Treatment of Age‐related Macular Degeneration (AMD) with PDT (TAP) study.

Methods: A record of all patients who first received PDT with verteporfin at The Royal Victorian Eye and Ear Hospital between the time of its introduction in February 2000 and February 2001 was prospectively maintained. The medical charts of these cases were reviewed and fluorescein angiograms were graded. Eyes with AMD were classified into three groups: TAP comparable if they had predominantly classic subfoveal choroidal neovascularization (CNV) and visual acuity between 6/12 and 6/60; VIP comparable if they had occult but no classic subfoveal CNV and visual acuity better than 6/36; and PDT ineligible if they fell outside recommended eligibility guidelines of the TAP/VIP studies. The main outcome measure was visual acuity change, with total number of treatments a secondary outcome variable.

Results: A total of 136 eyes of 130 patients began PDT during this period. The baseline angiogram and clinical data were available for 123 eyes (90%), and these were reviewed. Fourteen eyes had non‐AMD related CNV, while 109 eyes of 105 patients had AMD. Of the 109 AMD related lesions, 72 (66%) were TAP comparable, six (5.5%) were VIP comparable and 31 (28%) were PDT ineligible. At the 12‐month visit the proportion of TAP comparable eyes with same or better vision was 36/72 (50%), compared to 13/31 (42%) of the PDT ineligible eyes (P = 0.45). Only 30/72 (42%) of the TAP comparable eyes were still undergoing regular angiographic and clinical assessment (similar to the TAP protocol) at the time of the 12 month visit. The number of these who had same or better vision at 12 months was 17/30 (57%) compared to 19/42 (44%) TAP comparable eyes without regular angiographic follow up to 12 months (P = 0.37).

Conclusions: When used according to the guidelines estab­lished by the TAP study, the visual acuity results with PDT approached those achieved in the TAP study. When eyes were either enrolled outside the TAP study eligibility guidelines, or were not actively followed up over the 12‐month period as per TAP study guidelines, the visual outcome was similar to natural history of CNV secondary to AMD.
Measurement of the economic impact of visual impairment from age‐related macular degeneration in Australia
Authors: Hopley Charles , Carter Rob , Mitchell Paul
Published: November 2003

The purpose of this report was to: (i) outline the potential value of health economic studies into age‐related macular degeneration (AMD); (ii) provide an overview of health economic studies pertinent to AMD; and (iii) outline the basic frame work of cost‐of‐illness studies (a useful first step in applying economic methods). The detection and management of sensory loss in the elderly plays a key role in the Australian Government's Healthy Ageing Strategy. Age‐related macular degeneration is currently the leading cause of blindness in elderly Australians. Although a large proportion of AMD cases remain untreatable, the introduction of photo­dynamic therapy provides a relatively expensive and possibly cost‐effective innovation for others. Antioxidant therapy has also been proven effective in reducing progression of early to late disease. The discipline of economics can contribute to an understanding of AMD prevention and treatment through: (i)describingthe current burden of disease; (ii)predictingthe changes in the burden of disease over time, and (iii)evaluatingthe efficiency of different interventions. Cost‐of‐illness studies have been performed in many fields of medicine. Little work, however, has been done on describing the economic impact from AMD. A number of different economic evaluation methods can be used in judging the efficiency of possible interventions to reduce the disease burden of AMD. Although complementary in nature, each has specific uses and limitations. Studies of the economic impact of eye diseases are both feasible and necessary for informed health care decision‐making.