1997年 · 第110卷第11期

OBJECTIVE To investigate the allelic heterogeneity of the ATP7B gene in Chinese patients with Wilson's disease (WD). METHODS Exons of the ATP7B gene from 141 WD patients' DNA were amplified with polymerase chain reaction (PCR) 887-890. Mutations were then screened by single strand conformation polymorphism (SSCP) analysis and further identified by sequencing. RESULTS The molecular structure of exon 7 of the ATP7B gene from 141 WD patients was analyzed. The same band shift in electrophoretic pattern of 4 cerebral type patients was identified with SSCP and subsequently sequenced. The results showed missense mutation at the second base of the codon as Ser 662 Cys, which is caused by a C to G transversion. CONCLUSIONS Mutations of the ATP7B gene were investigated for the first time in China and a novel missense mutation was identified in four cases.

OBJECTIVE To investigate the effect of acoustic overstimulation on concentrations of cations in cochlear endolymph and analyze the relationship between the ionic changes in endolymph and the hearing loss. METHODS The endocochlear potentials (EP), K+, Na+ and Ca2+ concentration in cochlear endolymph were examined in vivo for normal and 167±2 dB SPL impulse noise exposed groups of guinea pig bored on time course by means of double-barreled ion-selective microelectrodes. Brain stem auditory evoked potential (BAEP) was used to evaluate the auditory function. Ca(2+)-ATPase activity was demonstrated cytochemically in the lateral cochlear wall as induced by Ando et al with slight modification. RESULTS The K+ and Ca2+ concentration exhibited significant changes in 8-hour groups (P<0.05 for K+ and P<0.01 for Ca2+). Then the K+ concentration was eventually resumed to the initial levels in accordance with the EP recovery in 7 days, while during the same period Ca2+ concentration was always significantly higher than that in control group (P<0.01). The BAEP threshold shifts were correlated well with changes in ionic concentrations, especially Ca2+ (P<0.001), in the endolymph induced by acoustic trauma. Although the normal positive EP was observed 7 days after noise exposure, the function of the vascular stria was not completely restored as revealed by the fact that the Ca2+-ATPase was diffused to the apical membrane surface. CONCLUSIONS Endolymph compartment intrinsic mechanism for maintaining ionic composition is seriously deteriorated after high impulse noise stimulation. The changes of the unique environment of endolymph may play an important role in the mechanism of sensorineural hearing loss induced by acoustic trauma.

OBJECTIVE To investigate the therapeutic effect of a new aqueous humor drainage (HAD) implant made in China for the treatment of refractory glaucoma. METHODS The implant was designed by ourselves and manufactured by Beijing Rubber Products Design and Research Institute. From July, 1993 to September, 1995, we observed 40 patients (41 eyes) with refractory glaucoma treated by implantation surgery, including 16 eyes with neovascular glaucoma (NVG) and 25 eyes with non-neovascular glaucoma (NNVG). RESULTS The mean period of postoperative follow-up was 9.2 (range, from 3-27) months, the intraocular pressure (IOP) was lowered from preoperative 7.20±1.51 kPa to postoperative 2.40±1.33 kPa in NVG group and from preoperative 6.27±1.07 kPa to postoperative 2.00±2.93 kPa in NNVG group. The success rate was 81% in NVG group and 84% in NNVG group. The common postoperative complications were flat anterior chamber, hyphema and choroidal detachment. CONCLUSIONS Our newly designed aqueous humor drainage implant is an economical implant in China and one of the alternative and effective methods for the treatment of refractory glaucoma. It can be widely used in clinics.

OBJECTIVE To evaluate the effect of early intervention on the intellectual development in asphyxiated newborn infants. METHODS Full term asphyxiated infants (Apgar score ≤6 at 5 minutes after birth) were randomly assigned to early intervention group (34 cases) and conventional care (30 cases) group. The normal control group consisted of 38 infants. Sex, mother's educational background, environmental condition and physical development were not significantly different in the 3 groups. Zero to two years early intervention program was compiled on basis of the national and foreign material about 1 month ahead of average development of the child. It included motor, cognitive, speech development and social behavior. Parents were instructed to carry out early intervention. RESULTS At the age of 1.5 years, average score of mental development index (MDI) in early intervention group was 14.6 higher than that in conventional care group (F=18.86, P<0.0001). MDI score in early intervention group caught up with that in normal control group (F=2.17, P>0.05). Conventional care group was 9.7 lower than normal control group (F=10.14, P<0.01). Two of 30 cases (6.7%) in conventional care group was mentally retarded while none was mentally retarded in the early intervention group. CONCLUSIONS The results showed that the early intervention could promote intellectual development of asphyxiated infants and be of much benefit to the prevention of mental retardation.

OBJECTIVE To investigate, at transcriptional and translational level in situ, whether the gene expression of the Ki-67 protein in pancreatic carcinoma specimens is altered to get insight of the gene structure and function. METHODS Forty pancreatic cancer, 5 normal pancreatic and 4 chronic pancreatitis tissues were used in this experiment. A 435 bp cDNA fragment located in codon 2, exon 13 of Ki-67 antigen gene was amplified by the polymerase chain reaction (PCR). The DIG-labeled cRNA probes were transcribed using a commercial DIG RNA labeling kit. Localization of the Ki-67 protein and the specific mRNA was performed by combining immunohistochemistry (ICH) with DIG-labeled in situ hybridization (ISH). RESULTS Successful localization of the Ki-67 protein mRNA in pancreatic tissue sections, routinely formalin-fixed and paraffin-embedded, was first accomplished in this experiment. Analysis of the Ki-67 mRNA transcription in 17 pancreatic cancer specimens with Ki-67 ICH labeling index>20% revealed stronger mRNA signals in poorly differentiated specimens with Ki-67 index>50% than in well differentiated cases with the ICH labeling index of 20%-50%. A high expression of both the mRNA and the protein was observed in pancreatic adenocarcinomas with poor differentiation. CONCLUSIONS This is the first study in which the abnormal overexpression of the gene encoding Ki-67 protein was detected not only at the protein level, but also at the mRNA level in pancreatic tumours. The abnormal overexpression of the Ki-67 protein might be correlated with the central part, exon 13, of the gene.

OBJECTIVE To assess the existence of a possible infectious factor in varicocele-related infertility. METHODS A total of 925 seminal plasmas from 590 infertile men with varicocele and 335 infertile patients without palpable varicocele were cultured for Ureaplasma urealyticum infection, and routine semen analysis was made. RESULTS The infection rate of Ureaplasma urealyticum in seminal plasmas was 48.22%. The asymptomatic genital infection of Ureaplasma urealyticum was traced in 329 (55.76%) varicocele men and 117 (34.93%) infertile patients without varicocele (control group). A significant quantitative difference in the incidence of genitalUreaplasma urealyticum infection between the varicocele and control group was observed (P<0.005) and asthenozoospermia was significantly more prevalent in the patients with varicocele than in the other patients (P<0.05). CONCLUSIONS Genital Ureaplasma urealyticum infection may play a role in varicocele-related infertility. To prevent future infertility, men with both varicocele and genital Ureaplasma urealyticum infection may benefit from early evaluation and treatment.

OBJECTIVE To evaluate the results of primary surgical treatment of carcinoma of oral tongue in Hong Kong. METHODS Patients who had undergone primary surgical treatment of oral tongue carcinoma in Queen Mary Hospital were reviewed. RESULTS There were 112 patients in this study. The first sites of tumor recurrence were 10 (9%) local, 25 (22%) nodal, 3 (3%) locoregional, 5 (5%) distant, 1 (1%) local and distant, 3 (3%) nodal and distant, and 1 (1%) neck extranodal site. Of the 63 T1-2 N0 M0 patients, the regional recurrence rate was 9% for elective neck dissection compared with 47% for "watchful waiting" (Chi-square test, P=0.0008). The regional recurrence related mortality was 3% for elective neck dissection compared with 23% for "watchful waiting" (Fisher's test, P=0.02). The 5-year actuarial survival rate was 86% for elective neck dissection compared with 55% for "watchful waiting" (Wilcoxon, P=0.01). CONCLUSIONS Local and regional recurrences were the main sites of treatment failure. Elective neck dissection has significant benefits in the reduction of regional failure and improvement of survival. Elective selective I-III neck dissection have to be considered in patients with stage I and stage II oral tongue carcinoma.

OBJECTIVE To recognize different forms of Guillain-Barre syndrome (GBS) in northern China. METHODS Twenty-one cases were found in two counties of Beijing suburb from January 1993, to December, 1994. Multiple electrophysiological studies including magnetic motor evoked potential, F-wave, motor and sensory conduction velocity, blink reflex and needle electromyography were conducted on nineteen cases of them. Twelve cases accepted electrophysiological follow-up study. RESULTS Altogether 17 cases showed demyelination features in multiple electrodiagnosis. Ten cases of them were accompanied by different extent of axonal lesion. Only one case showed main or primary axonal lesion. CONCLUSIONS Demyelination is the main type of pathophysiological lesion of GBS in Beijing suburb. Different extent of axonal lesion can appear in some cases, but primary and main axonal type is rare in this area.

OBJECTIVE To study the clinical, pathological and genetic characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS). METHODS Eight cases of MELAS (6 of them were from 2 families) underwent clinical study, muscle biopsy, autopsy on one patient, brain biopsy on one patient and genetic research. RESULTS In clinical report the average age of onset was 10-22 years old. Four cases from one family were 3 brothers and their nephew (sister's son). The death age of the three brothers was 16-20 years. Two cases from another family were a brother and a sister. The six patients of the two families showed the typical inherited characters of MELAS. The symptoms were myoclonic epilepsy, stroke-like episodes, paralysis of limbs, progressive mental retardation and neurological deaf. CT showed calcification in globus pallidus and MRI demonstrated clearly the abnormal prolongation of T2-weighed signals that distributed in frontal, parietal, occipital and temporal cortex as multiple focal, cystic and laminar necrotic areas. Pathological studies on brain showed multi-focal, cystic, and laminar or spongy necrotic abnormality primarily in gray matter of frontal, parental, temporal and occipital cortex. Decrease and loss of nerve fibers of the sub-cortical white matters of the lesion areas of cortex and calcification of globus pallidus were also observed. Red ragged fibers (RRF) and abnormal mitochondron were found by muscle biopsies. A point mutation (A-G transition) at nt 4243 in the mitochondrial tRNA Leu (UUR) was confirmed by using PCR and Southern Blot. CONCLUSIONS Although great progress has been made in the clinical, pathological and genetic research of MELAS, the pathogenesis of the disease remains further research.

OBJECTIVE To examine the effect of recombinant human transforming growth factor-β1 (rhTGF-β1) alone or recombinant human interleukin 6 (rhIL-6) alone or in combination on proliferation inhibition of the human leukaemia cell line. METHODS In the present study, using the human monoblastic cell line (U937) and human promyelocytic cell line (HL60) as an in vitro model, we analyzed the effect of two cytokins on proliferation inhibition with rate of 3H-TdR incorporation, the cellular content of DNA, DNA indices, the cell cycle and the expression of c-myc mRNA. RESULTS With administration of rhTGF-β1 and rhIL-6, U937 cell growth was inhibited and the rate of 3H-TdR incorporation inhibition was increased. There was a decrease in the cellular content of DNA and DNA indices. And no change in the cell cycle was observed after administration of rhTGF-β1 or rhIL-6. However, there was an increase in G0/G1 phase cells and a decrease in G2M + S phase cells after administration of combination of rhTGF-β1 and rhIL-6. It was also found that rhIL-6 could inhibit proliferative responses of HL60 cells, meanwhile the inhibition could be enhanced by rhTGF-β1. The rate of 3H-TdR incorporation inhibition rose up to 39.89%, and DNA index fell to 1.00 following induction by rhIL-6 plus rhTGF-β1. Furthermore, G0/G1 phase cells increased while G2M + S cells decreased. CONCLUSIONS These RESULTS suggest that combination of rhTGF-β1 and rhIL-6 acted in synergy to inhibit proliferation of both U937 and HL60 cell lines. Molecular hybridization test show that rhTGF-β1 alone, rhIL-6 alone or rhTGF-β1 and rhIL-6 in combination can inhibit U937 and HL60 cells expression of c-myc mRNA in a time and dose dependent manner. rhTGF-β1 and rhIL-6 in combination synergistically inhibited c-myc expression, which may be one of the machanisms for the actions of the two cytokines.

OBJECTIVE To review the research carried out in Hong Kong on nasopharyngeal carcinoma (NPC) over the past 10 years. METHODS The literature published in Hong Kong over the past 10 years on nasopharyngeal carcinoma were reviewed in the light of other important international publications on the same subject. RESULTS The research carried out in Hong Kong covers etiology, natural behavior, treatment and prognosis of NPC. These studies not only elucidated the different aspects of NPC, many of these new findings will also guide future directions of research. CONCLUSIONS Major efforts have been made to research into the various aspects of NPC with important findings which will translate into better treatment results. As this tumor is uncommon in other parts of the world, continued efforts to improve the prevention, early diagnosis, treatment and care of this tumor are required in China.

Purpose To review the current status of multimodality treatment and lymphadenectomy in the management of esophageal cancer. Data source Literature review. Study selection Multimodality treatment and lymphadenectomy in esophageal cancer. Data extraction Results in research papers published selected by literature search. RESULTS Numerous studies have been carried out attempting to define the roles of various neoadjuvant or adjuvant regimens in the treatment of esophageal cancer. These included the use of radiotherapy or chemotherapy alone or in different combinations, with or without surgical resection. Randomized trials have failed to show significant improvement compared with surgical resection alone, although downstaging of disease and benefits on subgroups of patients could be demonstrated. Whether the extent of resection can influence outcome was tested by varying the surgical approach, and by increasing the extent of lymphadenectomy. Although indirect evidence exists suggesting more extensive resection may improve long term prognosis, definitive proof is lacking. CONCLUSIONS More well organized randomized controlled trials are needed to further elucidate the roles of these approaches in the treatment of esophageal cancer.