Chemistry of human choriogonadotropin

Human choriogonadotropin is the placental member of the homologous glycoprotein hormone family which includes the pituitary hormones lutropin, follitropin and thyrotropin all of which share a common alpha subunit but different target-specific beta subunits. HCG differs chemically from the pituitary hormones by its higher carbohydrate content, high sialic acid content, lack of sulfation, longer plasma half-Life and capability to survive passage through the kidney essentially intact. Since crystallographic models are not available, hormone topography has been explored by immunochemical methods using both polyclonal and monoclonal antibodies. Studies of the immunochemistry of the beta COOH-terminal region have shown that determinants dependant upon carbohydrate content exist within this region. Such work also led to development of extremely sensitive and specific immunoassays for measurement of the hormone.     

Effect of desialylation of human chorionic gonadotropin on its metabolic clearance rate in humans

We determined the MCR and other kinetic parameters of desialylated hCG (as-hCG) in eight subjects (four men and four women), aged 20-47, using a single injection of 1 mg of a highly purified preparation. The plasma disappearance curve was fitted to a single exponential equation, with a half-time of disappearance of 3.56 +/- 0.62 min (mean +/- SD) and an initial volume of distribution of 1790 +/- 582 ml/m2. The mean MCR of as-hCG was 349 +/- 96 ml/min X m2. The mean transit time of as-hCG was 373 times shorter than that of hCG. The rapid plasma disappearance of as-hCG could not be accounted for by renal clearance into urine, since less than 0.05% of the as-hCG injected was excreted in the urine, nor could it be explained by degradation by plasma proteases, since as-hCG was not appreciably degraded during incubation in human serum at 37 C for 3 h. These data show that desialylation markedly accelerates the MCR of hCG in the human in spite of reduced renal excretion and, therefore, indicate the presence of a highly active pathway for uptake of desialylated glycoproteins.     

Asbestos-related focal lung masses: manifestations on conventional and high-resolution CT scans

In 260 asbestos-exposed individuals evaluated by means of computed tomography (CT), 43 unsuspected pulmonary masses were found in 27 individuals. The masses included fissural pleural plaques (n = 10), dense fibrotic bands (n = 3), round atelectasis (n = 11), carcinomas (n = 3), and other presumed benign masses (n = 16). The most helpful features in the diagnosis of rounded atelectasis with CT were (a) contiguity to areas of diffuse pleural thickening, (b) a lentiform or wedge-shaped outline, (c) evidence of volume loss in the adjacent lung, and (d) a characteristic "comet tail" of vessels and bronchi sweeping into the margins of the mass. Less advanced areas of focal atelectasis had fewer classic features. Intrafissural pleural plaques were readily identified with high-resolution CT. In asbestos-related masses, the demonstration of stability over time is necessary. Careful interpretation of CT and high-resolution CT features and close surveillance can obviate the need for biopsy in the majority of instances.     

经肛门内镜显微手术治疗直肠绒毛状腺瘤和早期直肠癌31例

目的探讨经肛门内镜显微手术（transanal endoscopicmic rosurgery，TEM）治疗直肠绒毛状腺瘤和早期直肠癌的疗效。方法1995年11月～2003年12月，我院行TEM治疗直肠肿瘤31例。全麻下根据肿瘤位置选择合适的体位，经肛门插入特殊的手术直肠镜，保持CO2充气状态，在立体视镜和腔镜系统下，采用针形电刀或5mm超声刀将直肠肿瘤完整切除（黏膜下或全层切除），手术创口在腔内连续缝合。结果31例直肠肿瘤均获完整切除，切缘均阴性。手术时间45～220min，平均95min；术中出血量0～180ml，平均40ml。手术并发症：暂时性排气失控2例，急性尿潴留1例，慢性阻塞性气道疾病急性发作1例，因服用阿斯匹林而出现继发性出血1例。术后病理分期：pT0期16例，pTis期2例，pT1期7例，pT2和pT3期各3例。31例随访2～92个月，平均23个月，肿瘤无原位复发。结论TEM是治疗直肠绒毛状腺瘤和早期直肠癌的一种安全、有效的微创手术方法。     

44Sacral extracorporeal magnetic stimulation is an effective treatment for pelvic floor dyssynergia; Comparative study with biofeedback therapy

Background: Recent development of extracorporeal magnetic stimulation (ECMS) which uses current‐changing magnetic fields allows the induction of electrical stimulation in the desired deep tissue. Recent study showed the sacral nerve stimulation reduces corticoanal excitability that may play a functional role in anal continence mechanisms. Preliminary study shows that ECMS of sacral nerve can modify pelvic floor function and expel rectal balloon in patients with pelvic floor dyssynergia (PFD). Aims: To evaluate the effect of ECMS compared with biofeedback therapy (BF) in patients with PFD. Methods and Materials: Thirty‐eight patients who fulfilled Rome II criteria for PFD by colon transit time and anorectal function tests, were randomly treated with 8 sessions of ECMS (2/weeks; n = 19) at prone position or BF (2/weeks; n = 19) at sitting position. Stimulation parameters were set at 50–80% of maximum intensity, 10 and 50 Hz frequency, 3 s burst length with 3 and 6 s off using arm‐typed stimulator (BioCom‐1000, Mcube Co., Korea). Symptom scores for constipation with/without anorectal function test were repeatedly measured after each treatment. Response was defined as 50% or more decreased symptom score after treatment (partial response: 30–50%, poor: <30%). Results: Fifteen patients (age 49.1 ± 13.4 years, mean ± SD; 4 men) completed 8 session of BF and 14 patients (54.5 ± 17.6 years, 3 men) completed 8 session of ECMS. Four patients of BF group discontinued treatment due to unsatisfactory therapeutic effect (n = 1) and withdrew consent (n = 3) and 5 patients of ECMS group discontinued treatment because of same reasons (n = 1, 4). Total symptom scores were significantly decreased after treatment of 8 session in both treatment groups (13.4 ± 6.6 vs. 4.3 ± 4.0 for BF, p = 0.009; 14.9 ± 5.6 vs. 3.4 ± 4.0 for ECMS, p < 0.001). Bowel movements per week were also significantly increased after treatment in both groups (median 2 vs. 7 for BF, p = 0.035; median 2 vs. 7 for ECMS, p = 0.008). Thirteen out of 15 patients showed response in BF group and 12 out of 14 showed good response in ECMS group. No adverse effects in both groups. Conclusions: ECMS is as effective as BF for the treatment of PFD. Long‐term effect of ECMS for the patients with pelvic floor dyssynergia need to be evaluated in the near future.     

Flashlamp-excited dye laser therapy of idiopathic vulvodynia is safe and efficacious

Objective: The management of chronic vulvovaginal pain, not explicable on specific histologic grounds, presents a major problem in referral centers for lower genital tract diseases.Study design: This article reports on a two-step protocol in a sample of 175 medical nonresponders, drawn from a 2-year cohort of 725 women with vulvovaginal pain. The first maneuver was the use of a flashlamp-excited dye laser to selectively photocoagulate symptomatic subepithelial blood vessels in 168 women; the second was the microsurgical removal of chronically painful Bartholin's glands in 52 women not responsive or not suited to flashlamp-excited dye laser photothermolysis.Results: Dye laser response rates werer independent of whether patients manifested macroscopic focl of painful erythema (“vestibular adenitis”) or just colposcopically apparent hyperemia-ectasia of the individual blood vessels (“pruritic papillomatosis”) (55% vs 45% after a single surgical procedure; 76% vs 65% after serial retreatment; p not significant). Conversely, response rates were much lower among women in whom pressure on the Bartholin's glands produced sharp, lancinating pain (15% vs 66% after a single surgical procedure; 22% vs 93% after serial retreatment; p < 0.001). Forty-two (85%) of 50 patients with flashlamp-excited dye laser failure had deep pain; however, the impasse to progress was broken by gland removal. Final response rates were 92.5% (complete response 62%; partial response 30%) in the “surface-only” group and 80.3% in the “surface-plus-deep” group (χ² = 14.9; p < 0.001). The major complication was acute bacterial cellulitis, occurring in the first postoperative week. Modification of the treatment protocol to include topical antibiotics with an occlusive dressing reduced the cellulitis rate from 17.2% to 2.5%. In four women (1.8%) Koebner-like exophytic condylomas also developed within 1 month of flashlamp-excited dye laser surgery.Conclusion: The availability of a safe, efficacious, and relatively noninvasive treatment should reduce the need for resective surgery in most patients with idiopathic vulvodynia. 1995; 172; 1684–1701.)     

CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme (GBM), the most malignant type of glioma, is the most common primary brainneoplasm. Although comprehensive therapeutic measures are applied, the prognosis of GBM remains dismal with a median post-treatment survival of less than one year.Modern molecular genetics has demonstrated thatabnormal alterations of tumor suppressor genes (TSGs) and oncogenes are the major mechanisms responsible for the initiation and progression of this malignant tumor.Identifying of related…     

High dosage pre-operative radiation and surgery for carcinoma of the larynx and laryngopharynx. A 14-year program

A carefully planned clinical program of combined pre-operative radiation and surgery has been conducted by the Department of Otolaryngology at The Mount Sinai Hospital for the past 14 years in an effort to improve the survival rates for advanced cancer of the larynx and laryngopharynx. The Combined Therapy Program, introduced in 1958, encompassed three separate but interdependent phases. The first stage consisted of a strict protocol of 5,500 rads of Cobalt 60 teletherapy administered over a five to six-week period. The second stage involved a rest period of three to six weeks to allow for proper healing of radiation reactions. The third stage comprised the radical procedure which included a wide field laryn-gectomy, ipsilateral hemithyroidectomy and radical neck dissection. Whenever indicated, a contralateral neck dissection was performed as soon as feasible. The protocol described above was applied only to those patients who fit all the criteria that categorized them as having advanced cancer of the larynx and laryngopharynx. In this study all patients had a biopsy proven diagnosis of squamous cell carcinoma. A very careful statistical analysis has been made of the survival experience of this series of cases. The three and five-year survival rates have been computed by the actuarial method,¹ which when compared to the direct method, adds more reliability to the results. The direct method removes those cases not treated at least three and five years ago in computing three and five-year survival rates, while the actuarial procedure includes all cases in the computation of survival rates. Between November, 1958, and March 1, 1972, 64 patients had been treated by combined therapy. According to the American Classification² the 64 cases are composed of 20 Stage II (T₂N₀ excluded), 12 Stage III and 32 Stage IV cases. According to the actuarial method the absolute survival rates for all cases were 77 percent and 59 percent for three and five years respectively. The corresponding determinate rates were 88 percent and 86 percent. Analyzing the results according to stages, the three-year determinate rates ranged from 100 percent for Stage II to 79 percent for Stage IV. The corresponding absolute rates ranged from 89 percent to 70 percent. The five-year determinate rates ranged from 100 percent to 74 percent, while the absolute five-year survival rates ranged from 50 percent for Stage II to 66 percent for Stage IV. This apparent reversal is far from being statistically significant because of considerable sampling error. The complications seen in patients treated with combined therapy have been essentially the same as those patients who undergo radical surgery without pre-operative radiation. Several preventive measures have been utilized during surgery, and it is to be emphasized that there have been no deaths related to complications, and all patients ultimately healed completely. The important controversy which exists in the- combined method of therapy concerns the question of using low dosage pre-operative radiation in the order of 1,000 to 3,000 rads or high dosages of radiation. It is our contention that serial section studies of biopsied laryngeal specimens labelled with tritiated thymidine tend to disprove the claims made favoring the value of low dosage radiation. The in vitro tritiated thymidine studies demonstrated that active DNA synthesis was observed in cancer cells in an appreciable number following dosages of 3,500 and also 5,500 rads.³ A further significant factor to be considered, we believe, is the effect of high dose pre-operative radiation on the incidence of cervical recurrence. In this series, 44 patients had clinically palpable nodes pre-operatively. There were six patients who developed local cervical recurrence, a rate of 14 percent. In conclusion, our statistics seem to indicate that our combined method of therapy has improved the survival rates of patients with advanced cancer of the larynx and laryngopharynx.