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[Study on the local immune system of the human pancreas and liver--ultrastructural localization of IgA and secretory component].

The localization of IgA and secretory component (SC) in human pancreas and liver was studied by the peroxidase-labeled antibody method. Ultrastructurally, SC was found in perinuclear spaces, in endoplasmic reticulum, in saccules associated with Golgi complexes, on basolateral membranes, in endocytic invaginations and in cytoplasmic vesicles of the pancreatic epithelial cells and the biliary epithelial cells. IgA was found in subepithelial connective tissues, in basement membrane and on basolateral membranes, in endocytic invaginations and in cytoplasmic vesicles of the cells in which SC was visualized. From the above findings, we concluded that IgA was transported into pancreatic juice and bile by SC-mediated vesicular transport mechanism across the pancreatic epithelial cells and the biliary epithelial cells. The presence of local immune system in human pancreas and liver is assumed to be one of the principal factors that prevent severe infection after surgical operation for the organs.

Biological Transport↗

Localized chronic pemphigoid of Brunsting-Perry. Ultrastructural localization of IgG and complement components.

Immune electron microscopic data are presented of a typical case of localized chronic pemphigoid (LCP) of Brunsting-Perry. The peroxidase-antiperoxidase multistep method for the electron microscopic localization of immunoglobulins and complement components showed that IgG, C3, and C4 were distributed in the lamina lucida and on the undersurface of the basal keratinocytes. These findings support the concept that LCP, bullous pemphigoid, and benign mucosal pemphigoid are closely related diseases. Unlike in bullous pemphigoid, however, complement was occasionally found in this case of LCP beyond the basal lamina in the uppermost portion of the dermis. This finding may explain the occurrence of scar formation in LCP.

Aged↗

Demonstration of a local exhaustion of complement components and of an enzymatic degradation of immunoglobulins in pleural empyema: a possible factor favouring the persistence of local bacterial infections.

Local bacterial infections such as abscesses or purulent exudates most often contain numerous, easily culturable bacteria despite an intense inflammatory reaction characterized by the ingress of polymorphonuclear leucocytes. In order to understand the mechanisms leading to such a persistent infection, we used pleural empyema as a model and measured the levels and catabolism of complement as well as of immunoglobulins in 28 infectious pleural effusions associated with either a positive or with a negative bacterial culture. Classic and alternative pathway haemolytic activities, factor B and C4 haemolytic activities as well as native C3 were markedly decreased or undetectable in most culture-positive effusions when compared to culture-negative effusions (P less than 0.005); breakdown products of factor B and C3 were markedly increased in culture-positive fluids. Eleven out of 14 culture-positive fluids exhibited IgG breakdown as opposed to none of the culture-negative fluids. In seven out of 14 culture-positive fluids, incubation with 125I-IgG led to their in vitro breakdown. This proteolytic activity could be abolished by preincubation of the culture-positive fluids with normal sera. Thus, increased catabolism of complement and breakdown of immunoglobulins, both leading to local consumption of immune reactants, could be one of the causes for bacterial persistence in pleural empyema.

Complement C3↗

Androgen receptor status in localized and locally progressive hormone refractory human prostate cancer.

Heterogeneity in human androgen receptor (hAR) expression in prostate cancer is considered to be implicated in tumor progression. hAR expression was therefore studied immunohistochemically in localized and locally progressive, hormone refractory (HR) prostate cancer. Because altered functional activity of the hAR may be due to changes in the structural integrity of the hAR gene, exons 2 to 8 of the hAR gene were assessed for mutations by single-strand conformation polymorphism (SSCP) analysis and exon 1 was analyzed for the size of the CAG repeat. The hormone binding capacity, a prerequisite for ligand-regulated receptor function, was determined by a ligand binding assay. Coexpression of the hAR and prostate-specific antigen (PSA) was studied by a sequential double immunoenzymatic staining to verify whether PSA expression is a parameter of hAR function. Almost all human prostatic carcinomas revealed heterogeneous hAR expression, regardless of tumor differentiation and progression. Putative predominance of hAR-negative tumor areas in HR prostate cancer was not observed. No hAR gene mutations or major changes in the CAG repeat were found in the 18 HR carcinomas or in the 9 control samples. Moreover, all selected hAR-expressing cancers were able to bind the synthetic androgen methyltrienolone (R1881). Immunoenzymatic double staining revealed even PSA expression in hAR-negative tumor areas. PSA immunohistochemistry in human prostatic carcinomas therefore is of no use in determining hAR functional activity. Thus, most prostatic carcinomas, even when progressed to a state of hormone insensitivity, contain a structurally intact hAR gene, heterogeneously expressed with retained androgen binding capacity.

Antibodies, Monoclonal↗

Imaging in the diagnosis and assessment of prognosis in localized prostate cancer. Consensus Conference on Diagnosis and Prognostic Parameters in Localized Prostate Cancer. Stockholm, Sweden, May 12-13, 1993.

As part of a WHO consensus conference on diagnosis and prognostic parameters in localized prostate cancer, a working group of experts discussed the role of various modern imaging techniques. Special attention was focused on transrectal ultrasound (TRUS) in combination with biopsies, magnetic resonance imaging (MRI) using endorectal coil and recent advances in these techniques. Some experimental techniques, especially hormone receptor scintigraphy and positron emission tomography were also discussed and new results were presented. We concluded that MRI seems to be superior to other imaging techniques in the preoperative assessment of local tumor stage. TRUS defends its place in the diagnostic armament; it is easily combined with multiple biopsies, the results of which are important in the assessment of the biological aggressiveness of prostate cancer. The present development in the field of nuclear medicine may result in techniques for in vivo characterization of tumors and will most certainly have important implications for diagnosis of prostate cancer in the future.

Animals↗

Cytoplasmic localization of a mutant M(r) 160,000 topoisomerase II alpha is associated with the loss of putative bipartite nuclear localization signals in a drug-resistant human lung cancer cell line.

Many clinically important antineoplastic agents exert their cytotoxicity through interaction with the M(r) 170,000 topoisomerase II alpha, an essential nuclear enzyme. Resistance to these agents has been associated frequently with either a decrease in the levels of topoisomerase II alpha or a qualitative change that alters the interaction of this enzyme with a drug or DNA. Using a VP-16-selected lung cancer cell line, H209/V6, we have identified a third resistance mechanism which involves an aberrant subcellular location of the topoisomerase II alpha isoenzyme. We have shown previously that H209/V6 cells express two topoisomerase II alpha mRNAs (6.1 and 4.8 kilobases) but only a single catalytically active protein which has a M(r) of 160,000 and is located primarily in the cytoplasm (Mirski et al., Cancer Res., 53: 4866-4873, 1993; Feldhoff et al., Cancer Res., 54: 756-762, 1994). In the present study we have determined that this mutant M(r) 160,000 topoisomerase II alpha is encoded by the shorter 4.8-kilobase mRNA. The sequencing of reverse transcriptase-PCR products from H209/V6 cells and subsequent Northern blot analyses showed that a sequence of 988 nucleotides from the 3'-coding and 3'-noncoding region of the normal topoisomerase II alpha is absent from the 4.8-kilobase mRNA. This shorter mRNA is predicted to encode a topoisomerase II alpha protein that no longer contains the 109 COOH-terminal amino acids of the normal enzyme but instead contains 34 new amino acids encoded by a sequence that was previously in the 3'-noncoding region of the mRNA. Confirmation that the COOH terminus of topoisomerase II alpha is no longer present in the M(r) 160,000 protein in H209/V6 cells was obtained by immunoblot analysis. Sequence analyses indicate that 3 putative bipartite nuclear localization signals in the M(r) 160,000 protein are disrupted or lost. Our results suggest that sequences within the COOH-proximal domain of human topoisomerase II alpha serve an important nuclear localization function.

Base Sequence↗

[Experimental study on local cooling of the eyeball in ocular surgery (4). The local cooling effect on uveal blood circulation, intraocular pressure, and intravitreous pressure].

The effects of local cooling on the uveal blood circulation, intraocular pressure, and intravitreous pressure were evaluated. Saline solutions maintained at 10 degrees C and 35 degrees C were dripped on the rabbit ocular surface. After 5-minute dripping of 10 degrees C saline solution, the temperature decreased by 10.6 degrees C at the ciliary body, 7.7 degrees C at the choroid and 2.9 degrees C at the central region of the vitreous. Hydrogen clearance with electrolytically generated hydrogen gas was employed to measure the tissue blood flow, which fell to 82.9% of normo-thermal value at the ciliary body and 86.3% at the choroid. The intravitreous pressure dropped by 2.8 mmHg. After 30-minute dripping of 10 degrees C saline solution, the intraocular pressure dropped by 3.0 mmHg. We consider that the reduction of intraocular and intravitreous pressure during local cooling of the ocular surface is related to decrease in the uveal blood flow.

Animals↗

Combinations of hormones and local therapies in locally advanced prostate carcinoma.

Locally advanced adenocarcinoma of the prostate (American Urological Association stages B2, C; American Joint Committee on Cancer stages T2c, T3) has been difficult to control by either external-beam irradiation or radical prostatectomy. The combination of local therapies with hormonal manipulation is an innovative strategy to combat this entity. Hormonal regimens have evolved to include total androgen suppression, or maximal androgen blockade. In phase III trials, it appears that the combination of irradiation and hormones is superior to the use of radiotherapy alone. Results of phase III trials comparing surgery to combinations of surgery and hormones have been less encouraging. To date, no prospective randomized trial comparing the combination of hormones plus surgery to hormones plus irradiation has been completed.

Androgen Antagonists↗

Rationale and clinical status of local hyperthermia, radiation, and chemotherapy in locally advanced malignancies.

The combination of ionizing irradiation and local hyperthermia therapy has been demonstrated to be efficacious in a variety of localized neoplasms. One of the most consistent conclusions from this experience, however, is the finding that large tumor size is a significant negative prognosticator for attaining complete tumor regression. During the past decade investigators have begun to look at the possibility of adding chemotherapy to thermo-radiotherapy in order to improve the efficacy of treatment in patients with large tumors. This review article summarizes the recent clinical experience with such triple modality therapy.

Antineoplastic Agents↗

[Localized and locally advanced renal cell carcinoma: method of outcome prognosis].

Basing on the long-term results of nephrectomy in 180 patients with renal cell carcinoma, the detailed assessment has been made of implications of a number of factors in 5-year survival and contribution of these factors to the disease outcome. The author proposes a method of prognosticating the disease outcome in patients with localized and locally advanced renal carcinoma which enables specification of the existing international classification and more precise prognosis of the disease. At stages T2, T3 and T4, 5-year survival reached in the subgroups with good prognosis 74.1, 100, and 30.8% of patients, respectively; with poor prognosis 7.1, 5.3, and 0%, respectively. Prognostic subgroup of the patient should be considered in the design of the treatment scheme.

Adolescent↗

[Tumescence local anesthesia. Improvement of local anesthesia methods for surgical dermatology].

The tumescent technique of local anesthesia was developed by J. Klein ten years ago to facilitate liposuction surgery. Tumescent anesthesia not only became the standard technique for liposuction, but proved to be of great value for other surgical problems in dermatology. Meanwhile, several noncosmetic uses for tumescent anesthesia were pioneered by dermatologic surgeons. This first review of the tumescent technique in German literature will focus on its specific advantages and disadvantages when applied in different fields of dermatologic surgery. Our own experience will be discussed, as well as future developments.

Anesthesia, Local↗

The National Survey of Local Anaesthesia for Ocular Surgery. II. Safety profiles of local anaesthesia techniques.

PURPOSE: To describe the adverse events associated with local anaesthesia (LA) for intraocular surgery. METHODS: An observational study of practice of LA in the whole of the United Kingdom was conducted over 3 months in late 1996. Staff in all ophthalmology theatres in the National Health Service were invited to report every LA given for the purpose of intraocular surgery during the first week, and thereafter to report adverse events only. RESULTS: During the first week, the reported incidence of all adverse events within the orbit was 2.7%, and for 'systemic' adverse events it was 0.9%. Serious adverse events were reported in association with all LA techniques. In 3 months, 18 events were described as 'life-threatening' by respondents, and further patients were reported to have had epileptic fits or were transferred directly from the operating theatre to an intensive care unit. The voluntary nature of the survey introduces some bias from under-reporting, making the incidence of these severe events difficult to assess. Reported incidence of severe 'systemic' adverse events was similar for all LA techniques. CONCLUSIONS: Serious adverse events were reported in association with with all LA techniques. This implies that we should be prepared for such events in all patients who have intraocular surgery.

Adult↗

Adductor Canal Block and Local Anesthetic Versus Local Anesthetic Alone in ACL Reconstruction: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Effective postoperative analgesia is crucial for early recovery after anterior cruciate ligament reconstruction (ACLR). Local infiltration analgesia (LIA) and adductor canal block (ACB) are common regional techniques, but their combined efficacy remains unclear. PURPOSE: To compare the effectiveness of LIA alone versus LIA combined with ACB in patients undergoing ACLR, with primary outcomes including postoperative opioid consumption and quadriceps function. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A double-blind randomized controlled trial enrolled 100 patients undergoing ACLR under general anesthesia. Patients were randomized into 2 groups: LIA + sham (saline injection) (n = 50) and LIA + ACB (n = 50). The primary outcome was postoperative opioid consumption in the first 24 hours. Secondary outcomes included visual analog scale (VAS) pain score, quadriceps function assessed by straight leg raise (SLR) at 3 hours, Quality of Recovery-15 (QoR-15) score, and Knee Injury and Osteoarthritis Outcome Score (KOOS) at 1 week. Statistical analysis was performed using t tests and chi-square tests with a P value <.05 considered significant. RESULTS: There was no significant difference in 24-hour opioid consumption between the LIA + ACB and LIA-only groups (P = .109). Similarly, VAS pain scores at 24 hours postoperatively showed no significant differences between the groups (P = .0804). Early functional recovery, assessed by SLR performance at 3 hours, was equivalent between groups (P = .6711). Additionally, QoR-15 scores on postoperative day 1 and KOOS values at 1 week demonstrated no significant differences (P = .6486 and P = .9054, respectively). Intraoperative opioid consumption was not different between the groups (P = .127). CONCLUSION: These findings indicate that the addition of ACB to LIA does not yield postoperative analgesic in ACLR. Consequently, LIA alone suffices for routine ACLR, potentially enabling clinicians to optimize perioperative workflows without incurring the additional time, financial burden, and resources associated with routine ACB administration. TRIAL REGISTRATION: ClinicalTrials.gov; NCT04721119.

Humans↗

[Decrease in paO2 following intratracheal application of a local anesthetic and a 0.9% sodium chloride solution. A prospective study on the use of fiberoptic bronchoscopy in ventilated patients during local anesthesia].

Flexible fiberoptic bronchoscopy of intubated patients can be performed in general or local anesthesia (LA). Up to now, no results have been published on the effects of LA for bronchoscopy in ventilated patients. We studied the hemodynamic changes caused by bronchoscopy under LA in mechanically ventilated patients and the effect of LA on the endoscopic decline in arterial pO2. Differences between the widely used agents lidocaine and oxybuprocaine hydrochloride were also studied. We found a decline in paO2 after the administration of LA and further investigated the influence of bronchial lavage on paO2. METHOD. A total of 70 ventilator patients, excluding patients with atelectasis, massive mucous-plug retention, and those under muscle relaxants, were examined in a surgical intensive care unit. In 40 long-term ventilator patients bronchoscopy was performed with either oxybuprocaine hydrochloride 1% (Novesin) (group 1; n = 20) or Lidocaine 1% (Xylocaine) (group 2; n = 20) (2-3 ml LA in repeated doses into the trachea and main bronchi; total amount 10 ml). We looked for hemodynamic changes and effects of LA on the bronchoscopic decline in paO2. In 15 long-term ventilator patients (group 3), LA was applied without bronchoscopy to investigate the duration of the LA-caused decline in paO2. In 15 intubated patients (group 4), the influence of intratracheal administration of 10 ml normal saline was examined. Patient data are shown in Table 2. Measurements were performed in groups 1 and 2 before and after LA, immediately after bronchoscopy and 15, 30, and 60 min after bronchoscopy and in groups 3 and 4 before and 5, 15, 30, and 60 min after LA. RESULTS. There was no effect on cardiocirculatory function during bronchoscopy in LA, but we found a decrease in paO2 after administration of LA in all patients (median in group 1 from 100 to 78 mmHg in group 2 from 104 to 86 mmHg). The subsequent bronchoscopy caused only a small, nonsignificant further decline in paO2. The administration of LA without bronchoscopy (group 3) was followed by a fall in paO2 from 86 +/- 12.5 to 69 +/- 11.7 mmHg (mean +/- SD) with oxybuprocaine hydrochloride and from 87 +/- 12.4 to 72 +/- 8.7 mmHg with lidocaine. Even after 30 min the paO2 had not returned to the initial value. The intratracheal application of 10 ml 0.9% NaCl caused a decline in paO2 from 101 +/- 20 to 78 +/- 12 mmHg (mean +/- SD), which also persisted for more than 30 min. CONCLUSIONS. The study shows that in ventilator patients undergoing fiberoptic bronchoscopy in LA, the administration of the LA is an essential factor in the decline in paO2 associated with bronchoscopy. A similar fall in paO2 is observed by intratracheal

Adolescent↗

[Use of the eutectic ointment EMLA (Eutectic Mixture of Local Anesthetics) in the surgical treatment of inguinal hernia under local anesthesia].

The use of EMLA eutectic cream is very effective and well tolerated in superficial anaesthesia. It is particularly indicated in surgical treatment of inguinal hernia by local anaesthesia, to achieve the analgesia of superficial layers. This allows to reduce the total dose of anaesthetics administrated by infiltration, reducing the risk of overdose, eliminating the pain due to injection, and is very agreeable for the patients.

Adult↗

A pilot study of combination therapy of radiation and local administration of OK-432 for esophageal cancer. Five-year survival and local control rate.

BACKGROUND: Combination therapy consisting of radiation and local administration of OK-432 was administered to 73 patients with esophageal cancer without distant metastases. Seventy patients were examined. The average age was 71 years. There were 60 males and 10 females. The mean tumor length was 7.0 cm. METHODS: One mg of OK-432 was administered endoscopically to and around the cancerous lesion at the beginning of radiotherapy and a second dose of 0.5 mg of OK-432 was given in the same manner 2 weeks later. X-ray irradiation was given at a daily dose of 1.6-1.8 Gy, five fractions a week. The average total dose was 61.1 Gy. RESULTS: Complete responses were obtained in 49 of the 70 patients (70.0%), and partial responses (PR) in the remaining 21. The 5-year cause-specific survival rate of the 70 patients was 33.1%. The 5-year survival rate of the 49 patients with CR was 44.9%, and there were no patients with PR who survived more than 2 years. The 5-year survival rate of the 13 patients with T1 (UICC, 1987) was 79.6%, of the 24 patients with T2/3 41.1%, and of the 33 patients with T4 11.6%. The 5-year survival rates of the 18 patients with tumors less than 5 cm in length and the 40 patients with tumors 5 to 10 cm were 59.9 and 37.9%, respectively. In the patients with tumors more than 10 cm in length, the 4-year survival rate was 14.6%. Sixty-nine of the 70 patients were discharged in good condition and were able to take food orally. CONCLUSIONS: This combination therapy may contribute not only to the survival rate, but also to patients' quality of life.

Aged↗

Hyperthermia improves local tumour control in locally advanced breast cancer.

We report three patients with advanced breast cancer who received hyperthermia (43 degrees C over 1 h, weekly x 4) and radiotherapy as palliative treatment for chest-wall recurrence. The case reports demonstrate situations where hyperthermia may be beneficial. These include tumours where radiotherapy alone is not expected to achieve control, such as large fungating tumours, and in previously irradiated areas. In these patients, hyperthermia with radiation achieves better local control of the tumour and delays the need for systemic chemotherapy. This may improve the quality of palliation.

Aged↗

Combined modality treatment for resected advanced non-small cell lung cancer: local control and local recurrence.

The purpose of this study was to compare the effect of post-operative thoracic radiation with or without systemic chemotherapy on survival and recurrence patterns in patients subjected to thoracotomy with curative intent, but subsequently found to have residual tumor in the resected margin or metastasis in the highest paratracheal lymph node. All patients were treated with postoperative mediastinal irradiation and randomized to receive or not receive combination chemotherapy (cytoxan, adriamycin, and platinum) for 6 months beginning concurrently with radiation. Of the 172 patients randomized, 164 were eligible for analysis. The mean time since randomization for the eligible patients is 4.2 years. Radiation therapy was administered to all patients by split course regimen [20 Gy in 5 fractions over 5 days]. Two such courses were given with a 3-week interval. The initial recurrence rates for both in-field recurrence and distant relapse were reduced in the combined postoperative radiation therapy and chemotherapy group, although only the latter difference achieved statistical significance (p = 0.01). Also, local recurrence overall (not restricted to initial recurrences) is examined as a function of histology, extent of residual disease after resection, and T and N status. The treatment effect achieves statistical significance only for patients with macroscopic residual (p = .023) or T3 tumor (p = .010). The combined therapy group of patients have a significantly longer recurrence-free survival [p = 0.006 by the two-sided Mantel-Haenszel logrank test] which fails, however, to translate to a significant difference in overall survival (p = 0.146). Median survival of the entire group is 14.5 months with 34% alive 2 years after resection. Most of the initial recurrences (82%) have been systemic, with brain being the most common site. Distant failure, therefore, remains an important problem even in the favorable prognosis subset of patients with advanced NSCLC, but combined modality approaches can produce improved recurrence-free survival.

Adenocarcinoma↗