[Experimental study of dopamine ameliorating the inflammatory damage of olfactory bulb in mice with allergic rhinitis].

Objective: To investigate the effects of dopamine on olfactory function and inflammatory injury of olfactory bulb in mice with allergic rhinitis (AR). Methods: AR mouse model was established by using ovalbumin (OVA), and the mice were divided into two groups: olfactory dysfunction (OD) group and without OD group through buried food pellet test (BFPT). The OD mice were randomly divided into 2 groups, and OVA combined with dopamine (3, 6, 9 and 12 days, respectively) or OVA combined with an equal amount of PBS (the same treatment time) was administered nasally. The olfactory function of mice was evaluated by BFPT. The number of eosinophils and goblet cells in the nasal mucosa were detected by HE and PAS staining. Western blotting, immunohistochemistry or immunofluorescence were used to detect the expression of olfactory marker protein (OMP) in olfactory epithelium, the important rate-limiting enzyme tyrosine hydroxylase (TH) of dopamine, and the marker proteins glial fibrillary acidic protein (GFAP) and CD11b of glial cell in the olfactory bulb. TUNEL staining was used to detect the damage of the olfactory bulb. SPSS 26.0 software was used for statistical analysis. Results: AR mice with OD had AR pathological characteristics. Compared with AR mice without OD, the expression of OMP in olfactory epithelium of AR mice with OD was reduced (F=26.09, P<0.05), the expression of GFAP and CD11b in the olfactory bulb was increased (F value was 38.95 and 71.71, respectively, both P<0.05), and the expression of TH in the olfactory bulb was decreased (F=77.00, P<0.05). Nasal administration of dopamine could shorten the time of food globule detection in mice to a certain extent, down-regulate the expression of GFAP and CD11b in the olfactory bulb (F value was 6.55 and 46.11, respectively, both P<0.05), and reduce the number of apoptotic cells in the olfactory bulb (F=25.64, P<0.05). But dopamine had no significant effect on the number of eosinophils and goblet cells in nasal mucosa (F value was 36.26 and 19.38, respectively, both P>0.05), and had no significant effect on the expression of OMP in the olfactory epithelium (F=55.27, P>0.05). Conclusion: Dopamine can improve olfactory function in mice with AR to a certain extent, possibly because of inhibiting the activation of glial cells in olfactory bulb and reducing the apoptotic injury of olfactory bulb cells.

[The sodium salicylate affects the expression of NMDA receptor and GABAa receptor subunits in spiral ganglion neurons of the cochlea through DA receptor].

Objective:To investigate mRNA expression of dopamine receptor subtypes in the rat cochlear spiral ganglion neurons (SGN) following exposure to the sodium salicylate. In addition, we observed the effect of sodium salicylate on N methyl-D-aspartic acid (NMDA) receptor subunit NR1 and gamma aminobutyric acid (GABA)a receptor subunit GABRα2 mRNA under the circumstance of DR activation or blocking. Moreover, we also focused on the the interaction between receptors mediated by SS.Method:Immunofluorescence techniques were applied to detect DR (DR1 and DR2) expression in cultured rat SGN. Moreover, RT-PCR was performed to assess NR1 and GABRα2 subunit mRNA.Result:Immunofluorescence images showed co-localization of DR1/DR2 and ßⅢ-tubulin protein in SGN bodies and axons. RT-PCR results illustrated that ①DR subtypes of DRd1-5 were detected in the SGN. ②The mRNA expression of all subtypes of DR and GABRα2, NR1 subunits were obviously upregulated except DRd3 after treatment with sodium salicylate. Among them, DRd1 expression increased 34.64%(t=-5.123,P=0.007),DRd2 expression increased 34.60%(t=-5.206,P=0.006),DRd4 expression increased 20.87%(t=-3.337,P=0.029),DRd5 expression increased 26.42%(t=-6.054,P=0.004),GABRα2 expression increased 30.41%(t=-2.839,P=0.047),NR1 expression increased 39.22%(t=-6.243,P=0.003).③After exposure to sodium salicylate (5 mmol/L), dopamine (100 µmol/L), DR1 agonist (SKF38393,20 µmol/L), DR2 agonist (Quinpirole,20 µmol/L), GABRα2 expression increased 21.78%,27.45%,33.02%,33.42% respectively (F=12.399,P=0.001),and NR1 expression increased 28.70%,26.82%,29.03%,35.05%(F=50.395,P=0.000) respectively.④Compared with the group of sodium salicylate treatment alone, both sodium salicylate + DR1 antagonist (SCH23390,20 µmol/L) group and sodium salicylate + DR2 antagonists (Eticlopride,20 µmol/L) group had a suppression on GABRα2 and NR1 mRNA expression.GABRα2 mRNA reduced 29.56%,37.10%(F=22.101,P=0.000) and NR1 mRNA expression decreased 37.62%,32.83% respectively(F=72.933,P=0.000).Conclusion:Most of the DR subtypes mRNA expression in SGN were increased following exposure to sodium salicylate. DR may be involved in the effect of sodium salicylate on GABAaR and NMDAR mRNA expression.

Nonaspiration puncture biopsy for suspected thoracic cavum tumor: experience of 2,010 clinical cases.

In our hospital from October 1980 to February 2000, 2,010 patients with suspected thoracic cavum cancer were diagnosed by nonaspiration puncture with multiple-hole type and surface trough-type biopsy needles. The positive rate of cytology or pathology examination for lesions in pleura, mediastinum, and lung tissue were 88.6% (148/167), 83% (297/358), and 80.2% (1,191/1,485), respectively. The mean positive rate in all cases was 81.4% (1,636/2,010). Complications rates for pneumothorax or hemoptysis were 1.3% and 0.8%, respectively, in this group. Such revised puncture needles have been used by us in various organs, such as brain tumors, metastatic lymph nodes of head and neck cancers, malignant disease of breast, liver, kidney, prostate, rectum and bone, etc. The use of such nonaspiration puncture needles is very simple, safe, and effective; even for beginners with this technique, the rate of successful diagnoses is fairly high.

Relationship between anal occult blood and hepatobiliary pancreatic carcinoma screening.

Cotton swab anal smear instead of stool occult blood test can not only be used as a mass screening method for colorectal cancer, but is an auxiliary way to screen hepatobiliary pancreatic carcinoma. Two hundred and twenty-three cases of hepatobiliary pancreatic carcinoma patients received anal occult blood test, of which 121 were positive (54.3%). The screening test was performed in 14,645 healthy people aged 40-60 years; 511 persons (3.4%) were positive for anal blood. Among these, six cases of digestive tract cancer were found (one oesophageal carcinoma, one gastric cardia carcinoma, two gastric carcinomas, two liver carcinomas). This suggests that when anal occult blood is positive, the patient should be scanned by ultrasonic means to rule out hepatobiliary pancreatic tumour.

Double blind randomized trial on occult blood bead (OBB) and gastroscopy-pathology screening for gastro-oesophageal cancer.

The study consists of two parts. In the first, 4,970 subjects were given the occult blood bead (OBB) test and 817 underwent gastroscopy: 40 of those screened were found to have cancer, 30 of which had early lesions (15 had carcinoma in situ). In the second part, a double blind randomized control study of the mass screening was conducted. All the tests were free of charge. Subjects over 30 years of age were persuaded to participate. Two-hundred and eight people accepted the OBB test, gastroscopy and histopathological assessment. A total of four cancers (two early, one moderate and one advanced) were detected by OBB test. If the OBB is carried out properly, gastro-oesophageal cancer is unlikely to be missed. We believe that OBB gastroscopy screening for oesophageal and gastric cancer is reliable and practical.

New concept for cancer screening.

Prevention of cancer mortality can be achieved by two main routes: (1) detection of precancerous lesions and preventing their progression to cancer, and (2) detecting cancers at an early stage when they are still amenable to curative treatment. Early detection of cancer is dependent on the population being well-informed about cancer, and about how to carry out self-examination as a preliminary screen (followed by a full clinical examination in the event of suspicious symptoms). In this paper the warning signs that the population should be taught to look out for are discussed. Superficial observation and palpation can be used for surface tumours (which comprise 10-15% of the total). A further 60-70% of tumours are of the digestive tract, respiratory tract or urogenital tract. For these, it is argued that a simple occult blood test could be used as a self-administered screening test. Data are presented to show that this is a practicable way for the general population to detect early signs of cancer or pre-cancer, with a high yield of clinically significant results in the occult blood positive persons.

Screening of esophageal and gastric cancer by occult blood bead detector.

A previously described bead method used to detect blood is simple, cheap, and effective; it can be repeated periodically. In 11 provinces in China, 233,825 persons (age range, 30-70 years) were screened. A positive occult blood test result was found in 28,557 persons (12%). Of these, 16,918 underwent a gastroscopy, resulting in the detection of 581 cancers that were located in similar frequencies in the esophagus, gastric cardia, and gastric body; 70% of the lesions were in an early or moderately advanced stage. Among 119 patients with early-stage cancer, the 3-year survival rate was 98.3%. After preliminary screening of cancer, the 4-year follow-up found a mortality rate in the group with negative occult blood test results that was only 25% of that of the positive group. Preliminary yearly screening would detect more early cancers and fewer advanced cancers. The mortality rate of esophageal and gastric cancer might be reduced drastically.

Sputum occult blood screening for lung cancer. Stage II screening of 14,431 subjects.

Sputum occult blood screening (SOBS) for lung cancer was performed in outpatients with suspected lung cancer. A total of 1011 patients were seen. Among them, 604 patients were found to be negative for SOBS, and 407 were found to be positive. The false-negative rate was 3.97% (24 of 604), and the opposite positive rate was 19.65% (80 of 407). A total of 14,431 normal subjects over 40 years of age were screened by SOBS. In the series, 1942 specimens were found to be positive. Among the 1942 patients, 31 were found to have definite cancer cells.

Influence of radiation on the blood-brain barrier and optimum time of chemotherapy.

A pilot study of the destructive effects of radiation on the blood-brain barrier (BBB) was made on 14 patients with localized and limited brain tumors by 99MTc-GH imaging from August 1988 to November 1989. Count/pixel data were obtained from the unirradiated, irradiated, and tumor areas before and after radiotherapy of 30-40 Gy. It was observed that, a) the BBB in the unirradiated area outside the radiation portal was not changed, b) the degree of destructive effect on the BBB in the irradiated normal area was directly proportional to the radiation dose. For 30-40 Gy, the count/pixel change enhances to average 24.7% [(147.6-118.4)/118.4], and c) the BBB in the tumor area is partially destroyed on an average of 22.1% [(206.8-169.4)/169.4] by the tumor. The radiotherapy further enhances this effect to an average of 74.7% [(206.8-118.4)/118.4]. Case 3 showed that before radiation, the degree of destructive effect on the BBB in the tumor area was 22% [(167-137)/137] higher than normal brain tissue. After a dose of 30 Gy of irradiation, it increased to 76.7% [(242-137)/137]; 8 months later it decreased to 17% [(160.3-137)/137]. It has been proven that the BBB can recover at least partially. Based on these observations, the authors believe that in the combined treatment of operated brain tumors, radiotherapy should precede chemotherapy so as to enhance the destruction of the BBB, facilitating the incorporation of drugs into the tumor. The dose at which to start chemotherapy is 20-30 Gy.

Management of local residual primary lesion of nasopharyngeal carcinoma: II. Results of prospective randomized trial on booster dose.

Although the question of booster dose for residual primary lesion arises in only 5% of nasopharyngeal carcinoma patients receiving radiotherapy, it poses a difficult problem for clinicians and should be followed. Hence, to test the validity of booster dose for residual primary lesion of nasopharyngeal carcinoma, a prospective randomized trial has been designed and carried out since January 1980. All patients who had a residual lesion in the nasopharynx at 70 Gy were biopsied. Those pathologically positive for cancer were randomized into two groups: (a) positive radiation group (PRG): patients were given further irradiation to a total dose of 90 Gy by the cone-down and assault technique, and (b) positive observation group (POG): patients were given no more irradiation but were followed periodically together with those who were pathology negative (NOG). A total of 78 patients were entered. The validity of booster dose was shown by the 5-year survival rates of the PRG, POG and NOG groups: 75% (3/4), 33% (1/3), and 58% (14/24), respectively. The total local recurrence rates of these groups were 6% (1/16), 36% (5/14), and 4% (2/48), respectively. The authors believe that booster dose for pathology positive residual lesion in the nasopharynx is necessary. The four factors leading to the development of a local recurrence are: (a) residual primary lesion proved positive by pathology but left unboosted, (b) well differentiated squamous cell carcinoma in the original primary lesion, (c) mild radio-response in the cancer parenchyma, and (d) mild radio-response in the interstitial tissue.

[Hemoccult test bead for screening of upper G-I tract cancer].

Hemoccult test bead is able to tell whether there is occult blood in the stomach juice or not. Screening test was carried out in the high incidence area for detecting the upper G-I tract cancer. The bead, swallowed and retained in the stomach for 3 minutes, was able to sort out the suspected individuals by its coloration: yellow (-), light blue (+), blue (++) and dark green ( ). 26261 normal subjects were screened in the high incidence area. The ages ranged from 35 to 70. 6353 (24.2%) of them showed positive results. Subsequent fiber-gastroscopy was performed for definite diagnosis in 2888 persons with positive results. 98 cancers were confirmed by pathology (26 in esophagus, 34 in gastric cardia, and 38 in stomach) with a detection rate of 3.4%. 73.5% of the cancer so discovered were in early stage. Factors influencing the cancer detection rate are sex, age and degree of positivity.

Management of local residual primary lesion of nasopharyngeal carcinoma (NPC): are higher doses beneficial?

One hundred and eighty-two nasopharyngeal carcinoma (NPC) patients, treated from March 1958 through 1978, received 70 Gy or more and were left with gross residual lesion in the nasopharynx, were retrospectively analyzed. Ninety-two patients were given a boost by reduced portals to a total of 90-120 Gy (boost group) whereas for the other non-randomized 90 patients, the treatment was stopped at 70 Gy (observation group). The local recurrence, distant metastasis and 5-year survival rates of the two groups are: 35% (32/92) vs. 58% (52/90), 20% (18/92) vs. 43% (39/90), and 54% (50/92) vs. 21% (19/90), respectively. The benefit of boost is more apparent in patients with T1-2 than T3-4 lesions (p less than 0.001), at increased risk of radiation encephalo-myelitis from 5.5% to 17%. The authors believe that boost be given to patients with early Stage T or small residual lesion at the primary site of NPC.

Chinese herb "destagnation" series I: Combination of radiation with destagnation in the treatment of nasopharyngeal carcinoma (NPC): a prospective randomized trial on 188 cases.

The results of a prospective randomized trial on 188 patients with NPC is reported to evaluate the validity of Chinese herbal medicine-Destagnation combined with radiotherapy. Ninety patients were allotted to the Destagnation group (radiation plus Destagnation) and 98, to the control group (radiation only). The 5-year success rate (number surviving minus number recurred but salvaged by re-treatment) of the Destagnation group is 53% (48/90) in comparison to 37% (36/98) of the control group (p less than 0.05). Minor complications of Destagnation included occasional anorexia and frequency of bowel movement. The reduced rate of local recurrence at the primary site in the Destagnation group (14%-13/90) as compared to that of the control group (29%-28/98) (p less than 0.05) suggests that Destagnation may be a radiosensitizer. The similar metastatic rates in both groups; 21% (19/90) in the Destagnation group and 21% (21/98) in the control group may refute the belief that Destagnation enhances hematogenous spread.

Screening for upper digestive tract cancer with an occult blood bead detector. Investigation of a normal north China population.

Screening of the general population for cancer of the upper digestive tract using an occult blood bead detector supplemented by fibergastroscopy was able to detect 126 cancers of the esophagus, gastric cardia, and stomach. This screening was carried out in two of the high-risk areas, Yangzhong and Wun counties, located in central eastern and north China. The occult blood bead detector, swallowed and retained in the stomach for 3 minutes, was able to sort out the suspected persons by its coloration from sky blue (+) to dark blue ( ) on removal. The subsequent fibergastroscopy could make a definite diagnosis by biopsy specimen. A preliminary trial performed on patients with established cancers was 100% (18 of 18) positive for stomach cancer and 81% (13 of 16) positive for esophageal cancer. A public survey of the high-risk areas, screening 38,073 normal persons ranging in age from 35 to 70 years, showed positive results in 9204 (24.2%) persons. Subsequent fibergastroscopy carried out in 4023 occult blood bead detector positive persons showed 126 cancers (41 of the esophagus, 46 of the gastric cardia, and 39 of the stomach). Factors influencing the cancer detection rate were sex, age, and degree of positivity of the occult blood bead detector test. Seventy per cent (89 of 126) of the cancers discovered were in an early stage. The occult blood bead detector costs the primary screened person only 30 cents and may be practical for the large-scale screening of cancer of the upper digestive tract in developing areas.

[Radiotherapy of nasopharyngeal carcinoma--analysis of 1379 patients].

This paper presents 1379 patients with nasopharyngeal carcinoma treated in our hospital from March 1958 to December 1978. The stage I and II lesions comprised 22% and stage III and IV lesions, 78%. 220 KV X-ray was used before 1960 and 60Co was predominant from 1961 through 1978. The overall 5 year survival rate was 41.4% (571/1379). Young adults and female patients gave better results. The 5 year survival rate was, according to pathological type, 45.1% for poorly differentiated squamous cell carcinoma and 13% for adenocarcinoma; according to clinical stage, 85.7% for stage I lesion, 59.5% for stage II, 45.8% and 29.2% for stages III and IV; according to period of treatment, 31.3% in the sixties and 48.6% in the seventies; according to tumor dose at the primary focus, 48.2% for 40-49 Gy, 55.6% for 60-69 Gy and 67.3% for 90 Gy or more; according to with or without prophylactic radiation in the neck region, 53.8% for the former and 23% for the latter. It implies that prophylactic radiation of the neck is necessary regardless of the presence of cervical lymph node metastasis or not. For those who had residual tumor at 70 Gy, the total dose may be boosted to more than 90 Gy with the cone down technic or the dose, at which the primary lesion disappears grossly, is added with 20 Gy. The common complications are radiation myelitis, trismus and otitis media. As in certain patients, the lesion would still recur 5 years after radiotherapy, the authors believe that the nasopharyngeal cancer patients should be followed for ten years at least.

Analysis of 1379 patients with nasopharyngeal carcinoma treated by radiation.

One thousand three hundred seventy-nine nasopharyngeal carcinoma (NPC) patients were treated from March 1958 to December 1978. Twenty-two percent had stage I or II and 78% Stage III or IV had lesions. Two hundred twenty-Kv radiographs were used before 1960; and telecobalt was used from 1961 to 1978. Factors influencing the 5-year survival rate favorably are youth of patient, being female, pathologic condition (poorly differentiated carcinoma, 45.1% versus adenocarcinoma, 13%), stage (Stage I, 86%, Stage II, 59.5%; Stage III, 45.8%; Stage IV, 29.2%), decade admitted for treatment in the past (31% in the 1950s, 48.6% in the 1970s), total dose delivered to the nasopharynx (40 to 49 Gy, 46%; 70 to 79 Gy, 54.1%; 90 Gy or more, 64%) and prophylactic radiation to the neck regions (with prophylactic irradiation, 53.8%, without prophylactic irradiation, 23%). This implies that prophylactic radiation of the neck is crucial even without positive clinical metastasis. For those who have a residual tumor in the primary site when 70 Gy has been delivered, the total dose may be boosted to more than 90 Gy with the cone-down technique or on basis of adding 20 Gy to the dose at which the primary lesion disappeared grossly. The common postirradiation complications are: radiation myelitis, trismus, and otitis media. Because disease recurred in some patients after the fifth year, NPC patients should be followed for at least 10 years.

Value of postoperative radiotherapy for thyroid cancer.

A series of 405 patients with thyroid cancer treated by surgery with or without postoperative radiotherapy from February 1958 through 1979 is reported. The immediate evaluation of the operation was that it was either incomplete or complete. Incomplete surgery implied that there was (1) possible residual tumor in the operative field, the result of difficult dissection of the tumor off the neighboring organs or tissues, as assessed by the surgeon; (2) multiple (more than five) lymph nodes involved; (3) positive border of the removed lesions; or (4) microscopic evidence of tumor in the operative field. Complete surgery implied through extirpation of cancer grossly and microscopically. In 297 patients who had complete surgery, 238 patients treated by surgery alone had a 5-year survival rate of 92% (218/238), while 59 patients who received postoperative radiotherapy had a 5-year survival rate of 78% (46/59). The optimum dose of postoperative radiotherapy was 50-70 Gy in 5 to 8 weeks, with the spinal dose kept under 40 Gy. Our experience shows that postoperative radiotherapy did not improve the survival of patients who had had complete surgery. Yet, in 108 patients who had incomplete surgery, surgery alone yielded a 5-year survival rate of 33% (19/57), while surgery plus radiotherapy yielded a 5-year survival of 71% (36/51). Our observation shows a remarkable benefit with postoperative radiotherapy in patients who have had incomplete surgery (P less than 0.05). According to pathologic criteria, postoperative radiotherapy was more effective in well-differentiated cancers than in poorly differentiated ones. It was equally effective in untreated as well as recurrent lesions. The prognosis for younger patients was better, but the sex of the patients did not affect prognosis.

[Occult blood detector for the upper G-I tract. I. A preliminary application in cancer screening].

The traditional chemical detection of small amount of blood in the stool can not tell whether the original bleeding site is in the upper or lower part of the G-I tract. The occult blood detector, designed by the authors, having a diameter of 8 mm, can easy be swallowed into the stomach with 30 to 50 ml of water. After remaining for 3 minutes in the stomach, it is pulled out by the patient himself and its coloration read to reveal the degree of bleeding. It can be used either by the medical personnel or the patient himself, at home, for the purpose of detecting minute bleeding in the upper G-I tract and for cancer screening in the high risk population. This detector gave a positive rate of 95% in patients with malignancies in the upper gastrointestinal tract. It is highly acceptable for its lack of discomfort during application. In cancer screening, it gave a positive rate of 5% to 10% in 10000 high risk persons. Those positive in this test showed a high incidence of gastric or esophageal cancers as proved by gastroscopy. This detector is being manufactured and sold by the Baiyunshan Pharmaceutical Factory, Guangzhou, Guangdong Province. Other papers concerning this topic are to be published.