A review of heart valve disease research in Malaysia.

INTRODUCTION: Heart valve disease comprises a cluster of conditions affecting the aortic, mitral, pulmonary and tricuspid valves. This paper reviews all the research on heart valve disease in Malaysia published between the years 2000- 2016. METHODS: The methodology was based on the search process described in the paper, "Bibliography of clinical research in Malaysia: methods and brief results". The search databases included PubMed, Scopus and several Malaysian journals such as MyJurnal and UKM Journal Repository, by using the following keywords: (heart valve disease OR infective endocarditis OR rheumatic heart disease) and (Malaysia). RESULTS: In all 94 papers were identified of which 39 papers were selected and reviewed on the basis of their relevance. The local studies contributed to the knowledge and understanding of the epidemiology, aetiology, pathophysiology, clinical presentations, investigations, treatment, and outcomes of heart valve disease in the country. DISCUSSION: The clinical relevance of the studies performed in the country is discussed along with recommendations for future research.

A review of aortic disease research in Malaysia.

INTRODUCTION: Aortic disease includes conditions such as chronic aortic aneurysms, acute aortic syndromes and congenital aortic abnormalities, amongst others. This paper reviews all research on aortic disease performed in Malaysia and published between 2000-2016. METHODS: A literature search was conducted in PubMed, Scopus, MyJurnal and the UKM Journal Repository. The search process was based on a previously published methodology. The medical subject headings (MeSH) search terms used were "aortic", "aorta" and "Malaysia". RESULTS: Two-hundred-thirteen papers were identified, of which 60 papers were selected and reviewed on the basis of their relevance. The epidemiology, pathophysiology, clinical presentations, case reports, investigations, treatment and outcomes of aortic disease in Malaysia were reviewed and summarised. The clinical relevance of the studies performed are discussed. CONCLUSION: The review provided an insight into the pathophysiology, prevalence and epidemiology of aortic diseases in Malaysia, how the condition is managed, and the outcomes of treatment. Limitations of the research performed in Malaysia to date were identified and recommendations for further research and improvement in clinical practice were recommended.

[Electrophysiological subtypes and long term prognosis of Guillain-Barré syndrome].

OBJECTIVE: To assess the electrophysiological subtypes of Guillain-Barré syndrome (GBS) acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN), and long-term prognosis in northeastern China. METHODS: One hundred and eighteen patients with GBS were recruited between 2010 and 2012 and retrospectively reviewed. RESULTS: According to electrodiagnostic criteria, patients were classified as AMAN (49, 46.7%) or AIDP (39, 37.1%), or were unclassified (17, 16.2%). Between the AMAN and AIDP groups, age, sex, and clinical disability did not differ significantly, but the AMAN patients more frequently had preceding gastroenteritis. By 4 weeks after onset, 24.5% of the AMAN patients (12) and 33.3% of the AIDP patients (13) had regained the ability to walk; by 1 year, 77.6% of the AMAN patients (38) and 79.5% of the AIDP patients (31) could walk. Recovery was generally favorable in both subtypes. Immunotherapy was effective in patients with either AIDP or AMAN, and glucocorticoids and immunoglobulin treatment could achieve similar effect. CONCLUSIONS: AMAN and AIDP are the main subtypes of GBS in northeastern China. The prognosis of patients with AMAN is similar to that of patients with AIDP. Different immunotherapies have similar effect on long term prognosis.

First Report of Nigrospora oryzae Causing Leaf Spot of Cotton in China.

Cotton (Gossypium hirsutum L.) is widely cultivated for the important economic value of the fiber. In the summer of 2011, a leaf spot of cotton plants cv. Wanza40 was observed in 11 fields (total of about 4 ha) in Qianshan County in southwest Anhui Province, China. Approximately 30% of the plants in each field were symptomatic. Affected plants exhibited brown to reddish, irregular foliar lesions, each with a brown border near the vein of the leaves. A sign of fungal infection was a dark leaf mold observed on lesions on the abaxial surface of leaves. Sections of symptomatic leaf tissues were surface-sterilized (in 75% ethanol for 30 s, then 1% NaOCl for 1 min), rinsed three times in sterile distilled water, and plated onto potato dextrose agar (PDA). A fungus consistently recovered from symptomatic leaf samples produced colonies that were initially white and then became grayish brown with the onset of sporulation. Black, spherical to subspherical, single-celled conidia (10 to 12 × 14 to 16 µm) were borne on a hyaline vesicle at the tip of each conidiophore. Morphological characteristics of the fungus were similar to that of Nigrospora oryzae (2). The internal transcribed spacer (ITS) region of ribosomal DNA (rDNA) from a representative strain of the fungus, AHC-1, was amplified using the primers ITS1/ITS4 (4) and sequenced (GenBank Accession No. JQ864579). The ITS sequence had 99% identity with >553 bp of the ITS sequence of an N. oryzae isolate (GenBank Accession No. EU918714.1). On the basis of morphological data and ITS rDNA sequence, the isolate was determined to be N. oryzae. A pathogenicity test was performed on detached, young leaves of 4-month-old healthy cotton plants of cv. Wanza40. Six leaves were inoculated by placing a colonized agar piece (5 mm in diameter) from 7-day-old cultures of the fungus on pushpin-wounded leaves. Another six leaves treated with sterile PDA plugs served as a negative control treatment. Leaves were incubated in petri dishes and maintained at 25°C in a growth chamber programmed for 12 hours of fluorescent white light/day. After 5 days, brown to black lesions were observed on all inoculated leaves, whereas no symptoms developed on control leaves. N. oryzae was consistently reisolated from symptomatic leaves but not from the control leaves. N. oryzae is a weak pathogen on a wide range of plants, and has been described as the causal agent of lint rot on cotton (1,3), but to our knowledge this is the first report of N. oryzae causing a leaf spot of cotton in China. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, ARS, USDA, Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , April 8, 2012. (2) H. J. Hudson. Trans. Br. Mycol. Soc. 46:355, 1963. (3) A. J. Palmatter et al. Plant Dis. 87:873, 2003. (4) T. J. White et al. In: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

First Report of Leaf Blight Caused by Nigrospora sphaerica on Curcuma in China.

Curcuma (family Zingiberaceae) is commonly cultivated for the use of rhizomes within traditional Chinese medicines. In October 2009 and 2010, severe leaf blight was observed on Curcuma wenyujin Y.H. Chen & C. Ling (4) in fields located in Ruian, China. The area of cultivation in Ruian encompasses 90% of the production in Zhejiang Province. Disease incidence was approximately 90% of plants observed in affected fields. Early symptoms were yellow-to-brown, irregular-shaped lesions on the leaf margin or tip. After several days, lesions expanded along the mid-vein until the entire leaf was destroyed. Blighted leaves turned grayish to dark brown and withered, and severely affected plants died. Eight fungal isolates were recovered from symptomatic C. wenyujin leaves, collected from eight different fields, on potato dextrose agar (PDA). These fungal colonies were initially white, becoming light to dark gray and produced black, spherical to subspherical, single-celled conidia (14 to 17 × 12 to 15 µm), which were borne on a hyaline vesicle at the tip of the conidiophores. On the basis of these morphological features, the isolates appeared to be similar to Nigrospora sphaerica (2). Strain ZJW-1 was selected as a representative for molecular identification. Genomic DNA was extracted from the isolate, and the internal transcribed spacer (ITS) region of the ribosomal DNA (ITS1-5.8S-ITS2) was amplified using ITS1 (5'-TCCGTAGGTGAACCTGCGG-3') and ITS4 (5'-TCCTCCGCTTATTGATATGC-3') primers (3). The ITS region was further cloned and sequenced (GenBank Accession No. JF738028) and was 99% identical to N. sphaerica (GenBank Accession No. FJ478134.1). On the basis of morphological data and the ITS rDNA sequence, the isolate was determined to be N. sphaerica. Pathogenicity tests were conducted on four leaves of four C. wenyujin plants by placing agar pieces (5 mm in diameter) from 8-day-old cultures on pushpin-wounded leaves. An equal number of control plants were wounded and inoculated with noncolonized PDA agar pieces. Plants were placed in moist chambers at 25°C with a 12-h photoperiod. Brown-to-black lesions were observed on wounded leaves after 3 days and expanded to an average of 56 × 40 mm 15 days after inoculation. No symptoms developed on the control leaves. The pathogen was reisolated from the margins of necrotic tissues but not from the controls. The pathogen has been reported as a leaf pathogen on several hosts worldwide (1). To our knowledge, this is the first report of N. sphaerica as a leaf pathogen of C. wenyujin in China. Future research will focus primarily on management of this disease. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases, Systematic Mycology and Microbiology Laboratory, USDA-ARS, Retrieved from http://nt.ars-grin.gov/fungaldatabases/ , March 31, 2011. (2) E. W. Mason. Trans. Brit. Mycol. Soc. 12:152, 1927. (3) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990. (4) J. Zhao et al. Molecules 15:7547, 2010.

Effect of lncRNA MALAT1 on rats with myocardial infarction through regulating ERK/MAPK signaling pathway.

OBJECTIVE: To explore the effect of the long non-coding ribonucleic acid (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on rats with myocardial infarction (MI) by regulating the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway. MATERIALS AND METHODS: The Sprague- Dawley (SD) rat model of MI was established, and lncRNA MALAT1 was overexpressed using pcDNA-MALAT1 plasmids (MALAT1 group, n=10) and silenced using RNA interference technique (siMALAT1 group, n=10). The Sham group (n=10) was also set up. The transfection efficiency of lncRNA MALAT1 in rats was detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). 2 weeks after the successful modeling, the cardiac function indexes were measured through magnetic resonance imaging (MRI) and echocardiography (ECG). The myocardial tissue injury was observed via hematoxylin-eosin (HE) staining, and the apoptosis of myocardial tissues was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Moreover, the levels of the serum inflammatory factors were detected via enzyme-linked immunosorbent assay (ELISA), the messenger RNA (mRNA) expressions of Collagen I and III, the apoptosis, the and pathway genes were detected via RT-PCR. The expressions of ERK/MAPK pathway-related proteins in myocardial tissues were detected via Western blotting. RESULTS: The expression of lncRNA MALAT1 was remarkably increased in the MALAT1 group but evidently declined in the siMALAT1 group (p<0.05), indicating the successful transfection. The fractional shortening (FS, %) and ejection fraction (EF, %) were significantly restored in siMALAT1 group (p<0.05), suggesting that the silence of MALAT1 can improve the cardiac function after acute MI. The results of the HE staining and TUNEL assay manifested that siMALAT1 group had milder myocardial injury and decreased apoptosis compared with MALAT1 group. In the MALAT1 group, the mRNA expressions of Collagen I and III, Caspase3, ERK2, and MAPK were remarkably increased (p<0.05), while the mRNA expression of Bcl-2 was remarkably decreased (p<0.05). The above expressions had the opposite trends in siMALAT1 group. Besides, the protein expressions of ERK2 and MAPK in MALAT1 group were significantly increased (p<0.05). CONCLUSIONS: The downregulation of lncRNA MALAT1 can significantly improve the cardiac function after MI in SD rats mainly by inhibiting the ERK/MAPK pathway.

Neuroprotective effects of α-lipoic acid on long-term experimental autoimmune encephalomyelitis.

OBJECTIVE: Experimental autoimmune encephalomyelitis (EAE) is an animal model commonly used in research on the acute phase of multiple sclerosis (MS), but studies on the pathology and pathogenesis of EAE with a long disease course are seldom conducted. Besides its antioxidant properties, the comprehensive mechanisms through which α-lipoic acid (LA) affects EAE remain obscure. We here conducted the study to explore the possible mechanisms. MATERIALS AND METHODS: In this study, the following methods were used for investigating the effects of LA on long-term EAE: hematoxylin-eosin staining (HE) and electron microscopic examinations of pathological changes; Western blotting of ß-amyloid precursor protein (ß-APP) and myelin basic protein (MBP); Enzyme-linked immunosorbent assay (ELISA) of tumor necrosis factor-α (TNF-α), transforming growth factor-ß (TGF-ß), superoxide dismutase (SOD), malondialdehyde (MDA) as well as flow cytometry of CD4+CD25+FoxP3+ regulatory T cells (Tregs). RESULTS: The results showed: (1) diverse pathological features of long-term relapsing-remitting EAE; (2) relatively increased MBP and reduced ß-APP expression in LA recipients 180 days after onset; (3) down-regulated TNF-α and up-regulated TGF-ß levels in LA recipients 7 days after onset; (4) lower MDA and higher SOD levels in LA recipients 180 days after onset; (5) increased Treg levels in LA recipients 7 days after onset. CONCLUSIONS: Aside from oxidative stress, LA possessed anti-inflammatory and immunomodulatory effects on EAE. LA might be a promising candidate for MS treatment.

[Changes of proportion regarding consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above].

Objective: To investigate the changes of proportion on both consistent condom use and syphilis infection among low-fee female sex workers aged 35 and above (LFSW), in order to provide evidence for targeted intervention strategies. Methods: A total of six cities-Liuzhou city and Pingnan couty of Guigang city of Guangxi Zhuang Autonomous Region, Jinghong city of Xishuangbanna Dai autonomous prefecture and Dali city of Dali Bai autonomous prefecture of Yunnan province, Zhangjiajie city and Jianghua Yao autonomous county of Yongzhou city Hunan province were involved in this study, with 60 eligible participants needed in each city, estimated through a pre-study. The first cross-sectional survey was completed from October 2012 to January 2013. Face-to-face questionnaire interview was carried out to collect information on socio-demography, work-related information and condom use situation. Blood was collected for syphilis testing. The second cross-sectional survey was carried out from June to September, 2015 under the same procedure. Results: A total of 371 and 403 eligible participants were included in the first and second survey, respectively. When comparing the two surveys, we noticed that the average age showed a slight change, from 42.4 years to 43.8 years old (t=3.537, P<0.001) and the average price for every commercial sex exchange increased from 36.8 RMB to 49.5 RMB (t=11.961, P<0.001). In the first survey, 46.9% (174/371) of the participants had more than two years of experience working as LFSW, compared to 61.3% (247/403) in the second survey (χ(2)=16.125, P<0.001). Also, 46.9% (174/371) of the participants consistently used condoms with clients in the past month in the first survey versus 64.3% (259/403) (χ(2)=23.641, P<0.001) in the second one. Rates of syphilis infection were found from 15.9% (59/371) in the first survey reduced to 7.2% (29/403) in the second survey (χ(2)=14.533, P<0.001). Conclusion: Compared with the first survey, the proportion of consistent condoms use showed an increase. Although the proportion of syphilis infection decreased in the second survey, the scope did not meet the criteria on syphilis, set by the government. Targeted intervention strategies on condom promotion and syphilis control should be implemented consistently in this population.

Protein folding and the robustness of cells.

The intricate intracellular infrastructure of all known life forms is based on proteins. The folded shape of a protein determines both the protein's function and the set of molecules it will bind to. This tight coupling between a protein's function and its interconnections in the molecular interaction network has consequences for the molecular course of evolution. It is also counter to human engineering approaches. Here we report on a simulation study investigating the impact of random errors in an abstract metabolic network of 500 enzymes. Tight coupling between function and interconnectivity of nodes is compared to the case where these two properties are independent. Our results show that the model system under consideration is more robust if function and interconnection are intertwined. These findings are discussed in the context of nanosystems engineering.

[Expression of thrombus regulatory protein and myeloperoxidasein peripheral blood of adult with obstructive sleep apnea hypopnea syndrome].

Objective:To investigate the expression of serum TM and MPO in adult patients with obstructive sleep apnea hypopnea syndrome(OSAHS).Method: Ninety OSAHS patients who confirmed by PSG as OSAHS group. According to AHI, the patients were divided into 3 groups include heavy, medium and light, and 30 healthy outpatients were control group. The serum TM and MPO were determined by ELISA; TM and MPO were measured after comprehensive treatment in patients with severe OSAHS, and the correlation between TM, MPO and PSG were analyzed. Result: ①With the severity of OSAHS patients increased, the serum levels of TM and MPO increased gradually（F=20.761,21.433；P<0.01). There was no significant difference about the concentration of TM and MPO between light and control group（P>0.05）；The concentration of TM and MPO was significantly higher in heavy and medium group compared with light and control group（P<0.01）.②There was no correlation between serum levels of TM, MPO, BMI, age and sex in OSAHS patients(P>0.05). The serum concentration of TM was positively related to MPO. The serum concentrations of TM and MPO were positively correlated with AHI, but negatively with LSaO2 (P<0.05). ③LSaO2 was significantly increased, AHI and peripheral blood TM, MPO levels were significantly reduced in thirty severe OSAHS cases received the combined treatment(P<0.01).Conclusion:The increase of TM and MPO concentration in peripheral blood is one of characteristics of cardiovascular damage in patients with OSAHS. Combined detection of serum TM and MPO concentrations in patients with the disease is helpful for evaluation and risk assessment of cardiovascular disease.

[The effect of preoperative induction chemotherapy on long-term survival of patients with advanced squamous cell carcinoma of the oral cavity tongue].

Objective:To discuss the long term efficency of preoperative induction chemotherapy(IC)±radiotherapy on patients with resectable stage Ⅲ or Ⅳ squamous cell carcinoma of the oral cavity tongue(SCCOT).Method:During June 1996 to December 2005, 73 patients with locally advanced SCCOT treated preoperatively with IC(3 cycle of cisplatin and 5 fluorouracil) followed by surgery(resection of the primary tumor and neck)±radiotherapy in the Cancer Center of Sun Yat-sen University were enrolled in our study. Five-year overall survival rates(OS), local control rate and reasons of treatment failure were analyzed retrospectively.Result:The follow-up time was 1.9 to 188.0 months, and the median follow-up time was 70.9 months.Among that, 24 cases(32.9%) were still alive, of which 23 patients survival time is more than 10 years until the deadline of the follow-up. After IC, 17 patients(23.3%) had clinical complete response; 44 patients(60.3%) had a clinical partial response; 12 patients(16.4%) had no response or progression, and an overall response rate was 83.6%(65/73). On final surgical pathology, 14 patients(19.2%) had pathological complete response; 59 patients(80.8%) had histological incomplete response(residual tumor). Univariate analysis showed that the tumor size(P< 0.05), cervical lymphatic metastasis(P< 0.05),clinical stage(P< 0.05), the different clinical remissions(P< 0.05), had or not pathological complete remission(P< 0.05) were risk factors affecting prognosis(P< 0.05).Multivariate analysis indicated that cervical lymphatic metastasis cervical lymphatic metastasis(P< 0.05), the different clinical remissions (P< 0.05), had or not pathological complete remission(P< 0.05) were independent factors for prognosis. Five-year OS of clinical effective of IC was 62.5%, apparently higher than the invalid effect 41.7% (P< 0.05). Five-year OS of pCR was 92.9%, while have no pCR was 47.9%(P< 0.05). A significant difference between the two groups was also found. During whole follow-up time, 22 patients developed recurrence. Five-year OS was 59.8%, local control rate were 69.9%.Conclusion:IC plus surgery with or without postoperative radiotherapy was a treatment modality that was tolerated with encouraging activity and survival outcome in patients with advanced resectable SCCOT. Response rate with this IC regimen was limited, but the responders were associated with excellent prognosis.

[Clinical analysis of benign paroxysmal positional vertigo associated with Meniere's disease].

Objective:To explore treatment and therapeutic effectiveness of patients with Meniere' s disease and benign paroxysmal positional vertigo.Method: A series of BPPV 60 cases was retrospective analyzed. The patients were divided into three groups: Meniere' s disease with multiple semicircular canal BPPV(n=6), with single semicircular canal BPPV (n=11) and BPPV without Meniere' s disease group(Control,n=43). All patients were diagnosed by the Dix-Hallpike test or roll test and treated with the canalith repositioning procedure. The outcomes were compared among the three groups. Result: Unilateral semicircular canal BPPV was more than bilateral BPPV, the posterior semicircular canal was the most common canal involved, and multiple semicircular canal BPPV with Meniere' s disease patients needed repeated canalith repositioning procedure and had a higher recurrence rate.Conclusion:A lower success rate of treatment and a higher recurrence rate was found in BPPV patients with Meniere' s disease compared with those without Meniere' s disease . The recurrence rate is highest in multiple semicircular canal BPPV with Meniere' s disease.

Effects of prolactin on steroid production by human luteal cells in vitro.

The effects of prolactin on steroidogenesis were studied in dispersed luteal cells prepared from human corpora lutea of the menstrual cycle. Prolactin, at concentrations of 0.1-1000 ng/ml, had no effect on progesterone production by luteal cells during short-term incubation (3 h). However, in two out of five corpora lutea, higher concentrations of prolactin (100 and 1000 ng/ml) significantly reduced the oestradiol-17 beta production induced by human chorionic gonadotrophin (hCG; 10 i.u./ml); lower doses of prolactin had little effect. In the remaining corpora lutea, prolactin failed to affect either basal or hCG-induced production of oestradiol-17 beta. These results are discussed in relation to the mechanism by which prolactin influences human ovarian function.

Oxytocin may play a role in the control of the human corpus luteum.

The effects of oxytocin on dispersed luteal cells from human corpora lutea of the menstrual cycle were studied. Oxytocin at a concentration of 4 mi.u./ml produced a slight increase in basal progesterone production. However, higher oxytocin concentrations (400 and 800 mi.u./ml) markedly inhibited both basal and human chorionic gonadotrophin-induced progesterone production. These data provide evidence for an effect of oxytocin on the human corpus luteum. In view of the inhibitory action of oxytocin, increased secretion of this hormone may be important in the demise of the corpus luteum at the end of the menstrual cycle.

Effect of oxytocin on plasma testosterone levels in the male macaques (Macaca fascicularis).

The effect of oxytocin on testicular function was examined in the adult male long-tailed macaques (Macaca fascicularis). The monkeys were either infused with increasing concentrations of synthetic oxytocin (16-128 m.i.u./min for 3 h) or injected daily for a week with the same hormone (20 i.u., i.v.) and the plasma testosterone levels measured. The results of the present study show that acute infusion or chronic injection of oxytocin does not significantly affect the plasma testosterone levels, suggesting that systemic control of testicular endocrine function by oxytocin may be unimportant.

Cross-sectional study of near-work and myopia in kindergarten children in Singapore.

INTRODUCTION: In view of the high and increasing myopia rates amongst young Singaporean children, we aimed to assess the relationship between near-work and myopia in 414 pre-school children aged 4 to 6 years. MATERIALS AND METHODS: We measured near-work indices such as tuition classes outside school and other possible risk factors via a questionnaire. We then measured myopia with a hand-held autorefractor. RESULTS: Children who had 3 or more hours per week of near-work classes outside school had a higher rate [odds ratio 1.39 (95% confidence interval 1.02, 2.53)] of myopia. CONCLUSIONS: This suggests that there may be an association between near-work and myopia, even at such a young age. Given the increasing emphasis on near-work in Singapore, it may be important to call for increased visual health awareness, although further studies will be needed to establish if near-work causes myopia.

Maintenance of pseudopregnancy by prolactin in indomethacin treated rats.

1. The effects of bromocriptine and indomethacin on prolactin-induced pseudopregnancy were studied in pituitary grafted rats. 2.Administration of bromocriptine (a prolactin suppressant drug) at a total dose of 3 mg/kg body weight, given in 3 divided doses on day 5 of pseudopregnancy, effectively terminated it within 3 days. However, injection of indomethacin (a prostaglandin inhibitor) at a total dose of 6 mg/kg body weight, given in 3 divided doses, on the same day of pseudopregnancy had no significant effect on its duration. 3. It appears unlikely that the luteotrophic effect of prolactin on the corpus luteum is mediated by the stimulation of prostaglandin synthesis.

Evaluation of prognostic characteristics of stage I cutaneous malignant melanoma.

The prognostic characteristics of stage I cutaneous malignant melanoma were evaluated. For this purpose, all patients with malignant melanomas diagnosed between January 1, 1967, and December 31, 1982, at the Department of Pathological Anatomy of the S.S.D.Z. were examined. Of the 187 total cases of malignant melanoma, 169 patients had stage I disease. Of these, 101 were not included in the investigation for the following reasons: carcinoma in situ (2), previous radiation treatment (1), localization in mucous membrane (2), microscopic sections unsuitable for morphometry and measurement of tumor thickness (11), follow-up period shorter than 60 months (61), lost for follow-up (12) and cause of death unrelated to melanoma (12). Of the remaining 68 patients, 46 had been alive without metastases for at least 60 months ("survivors") and 22 had died from metastases within 60 months ("nonsurvivors"). The following parameters were investigated: age, sex, localization, histologic type, level of invasion according to Clark and Breslow, ulceration, mitotic activity index, morphometric parameters (relating to nuclear shape and size) and number, size and localization of nucleoli. Wilcoxon's test and the chi-square test showed significant differences between survivors and nonsurvivors with regard to ulceration (P = 0.005), mitotic activity index (P = 0.006), histologic type (P = 0.03), level of invasion according to Clark (P = 0.004), Breslow tumor thickness (P = 0.003), standard deviation of nuclear contour index (P = 0.04) and nuclear correlation coefficient (P = 0.008). The results showed that tumor thickness of cutaneous malignant melanoma is the most significant prognostic parameter.(ABSTRACT TRUNCATED AT 250 WORDS)