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PubMed1987

Localized operable soft tissue sarcoma of the upper extremity. Presentation, management, and factors affecting local recurrence in 108 patients.

Radical ablative surgery for upper extremity sarcoma often results in significant loss of function. With the recent emphasis on limb preservation, function-sparing excision has been combined with adjuvant radiation and chemotherapy in an increasing number of patients. To assess the effect of changing management on local recurrence rates and identify factors governing local failure, the records of 108 patients with operable, nonmetastatic soft tissue sarcoma of the upper extremity, treated at the Memorial Sloan-Kettering Cancer Center between 1968 and 1978, were reviewed. Median follow-up care was 8.2 years. One third of the patients presented with locally recurrent tumors after initial treatment elsewhere. Over half of the lesions were above the elbow and 62% were high grade. Seventy-three patients (68%) had limb-sparing surgery (LSS), but margins were considered adequate in less than half. Local recurrence was directly related to the adequacy of the surgical margins and was significantly higher in the LSS patients (p = 0.008). Other factors associated with an increased risk of local failure included: presentation with local recurrence, superficial location, and invasion of vital structures (LSS only). Local failure varied significantly with histologic type and was highest in patients with embryonal rhabdomyosarcoma and angiosarcoma. When the data were subjected to multivariate analysis, the following variables emerged as independent predictors of local failure: presentation with local recurrence, surgery by LSS, inadequate margins, angiosarcoma, and invasion of vital structures. These risk factors should be carefully weighed when selecting local treatment for patients with upper extremity soft tissue sarcomas.

Adolescent↗
PubMed2001

[Local tumor control and (disease-free) survival after surgery with pre- and intraoperative radiotherapy for primary non-resectable rectal carcinoma and local recurrence].

OBJECTIVE: Survey of the results of multimodality treatment for primary irresectable rectum carcinoma and local recurrence of rectal cancer. DESIGN: Retrospective. METHODS: During the period 1 February 1994 to 31 August 1999, 43 patients with locally advanced primary rectal cancer (25 men and 18 women; mean age: 64 years (range: 36-86)) and 53 patients with a local recurrence (33 men and 20 women; mean age: 61 years (39-82)) were treated with a multimodality treatment: i.e. preoperative radiotherapy (doses 50.4 Gy, or 30.0 Gy in the case of reirradiation), extensive surgery and intraoperative radiotherapy (doses 10-17.5 Gy). This treatment took place at two hospitals in the Netherlands, the Catharina Hospital in Eindhoven and, since 1997, the Daniel den Hoed Cancer Centre in Rotterdam. In 2000 data were collected for the local control and (disease-free) survival; these were analysed using the Kaplan-Meier method. Patients also completed a questionnaire about the quality of life at a median period of 14 months (range: 4-60) after the operation; the response level was 96% (76/79). RESULTS: After 3 years, the local control, disease-free survival and survival rates for the locally advanced primary rectal cancer group were 74%, 60% and 55% respectively, and for the locally recurrent rectal cancer group 64%, 34% and 50% respectively. Tumour resection with microscopically negative margins had a statistically significant positive effect on the local control and disease-free survival in both groups as well as on the survival in the locally advanced primary patient group. Seven of the 96 patients (7%) died as a result of complications. Of the patients with a primary irresectable carcinoma or a local recurrent tumour who completed the questionnaire the results were as follows: 56% and 63% respectively had been able to resume employment, 53% and 59% respectively had been able to resume their previous lifestyle, 15% and 27% respectively indicated radicular pain as a new symptom, 26% and 46% respectively stated problems with walking, 42% and 44% respectively stated problems with urinating and 59% and 52% respectively a reduction in sexual activity.

Adult↗
PubMed2026

Morbidity and mortality from local anesthetics: localized and systemic toxicity.

PURPOSE OF THE REVIEW: Local anesthetics remain vital to modern medicine, yet their narrow therapeutic window continues to result in complications. This review synthesizes recent literature to define the current landscape of local anesthetic-associated adverse events. RECENT FINDINGS: Perioperative mortality attributable to local anesthetics persists despite sustained safety initiatives and professional society recommendations. Pharmacovigilance and case data identify lidocaine (oropharyngeal, topical, and via local infiltration) as the predominant contributor to adverse outcomes, including death. Local anesthetic systemic toxicity remains an issue, with a recent shift in epidemiology: an increasing proportion of toxic events originates from surgeon- and proceduralist-administered analgesia. Anesthesiologist-controlled methods also cause toxicity via catheter-based delivery and nerve blocks in highly vascular regions. Localized toxicity in the form of high neuraxial contributes to morbidity, with recent reviews reinforcing known risk factors; whereas localized neurotoxicity appears less troublesome when managed appropriately. SUMMARY: The cumulative evidence identifies shifts in the patterns of systemic and localized toxicities. Bupivacaine-based peripheral nerve blocks no longer represent the principal cause of complications because of the advent of ultrasound guidance and lipid emulsion therapy. In contrast, high neuraxial techniques persist as a cause of morbidity, accompanied by intravenous/oropharyngeal lidocaine, proceduralist-administered local infiltration analgesia, and catheter-based delivery.

Humans↗
PubMed2001

Local treatments for cutaneous warts.

BACKGROUND: Viral warts caused by the human papilloma virus represent one of the most common diseases of the skin. Any area of skin can be affected although the hands and feet are by far the commonest sites. A very wide range of local treatments are available. OBJECTIVES: To assess the effects of different local treatments for cutaneous, non-genital warts in healthy people. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (March 1999), the Skin Group trials register (March 1999), MEDLINE (1966 to August 2000), EMBASE (1980 to August 2000) and a number of other key biomedical and health economics databases. In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in local treatments for warts and experts in the field were contacted. SELECTION CRITERIA: Randomized controlled trials of local treatments for cutaneous non-genital viral warts in immunocompetent human hosts were included. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent reviewers. MAIN RESULTS: Forty-nine trials were identified which fulfilled the criteria for inclusion in the review. The evidence provided by these studies was generally weak because of poor methodology and reporting. In 17 trials with placebo groups that used participants as the unit of analysis the average cure rate of placebo preparations was 30% (range 0 to 73%) after an average period of 10 weeks (range 4 to 24 weeks). The best available evidence was for simple topical treatments containing salicylic acid, which are clearly better than placebo. Data pooled from six placebo-controlled trials show a cure rate of 144/191 (75%) compared with 89/185 (48%) in controls, odds ratio 3.91 (95% confidence interval 2.40 to 6.36), random effects model. Most of the bigger trials of cryotherapy studied different regimens rather than comparing cryotherapy with other treatments or placebo. Pooled data from two small trials that included cryotherapy and placebo or no treatment, showed no significant difference in cure rates. In two other trials comparing cryotherapy with salicylic acid no significant difference in efficacy was demonstrated. There was no consistent evidence for the effectiveness of intralesional bleomycin. Four studies, using warts rather than individuals as the unit of analysis, had widely varying results which could not be meaningfully pooled. There was some evidence for the efficacy of dinitrochlorobenzene, a potent contact sensitizer. Pooled data from two small studies comparing dinitrochlorobenzene with placebo showed cure rates of 32/40 (80%) and 17/40 (43%) respectively, odds ratio 5.42 (95% confidence interval 1.99 to 14.75), random effects model. Only limited evidence was found for the efficacy of topical 5-fluorouracil, intralesional interferons and photodynamic therapy. Bleomycin, dinitrochlorobenzene, 5-fluorouracil, interferons and photodynamic therapy are potentially hazardous or toxic treatments. REVIEWER'S CONCLUSIONS: There is a considerable lack of evidence on which to base the rational use of the local treatments for common warts. The reviewed trials are highly variable in method and quality. Cure rates with placebo preparations are variable but nevertheless considerable. There is certainly evidence that simple topical treatments containing salicylic acid have a therapeutic effect. There is less evidence for the efficacy of cryotherapy and no convincing evidence that it is any more effective than simple topical treatments. Dinitrochlorobenzene appears to be effective but no more so than the safer, simpler and cheaper topical treatments containing salicylic acid. The benefits and risks of 5-fluorouracil, bleomycin, interferons and photodynamic therapy remain to be determined.

Administration, Topical↗
PubMed1978

Local cerebral energy metabolism: its relationships to local functional activity and blood flow.

The results of studies with the [14C] deoxyglucose technique unequivocally establish that local functional activity in cerebral tissues is, as in other tissues, closely coupled to the local rate of energy metabolism. Stimulation of local functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. Local cerebral blood flow is normally distributed among the cerebral structures in almost exact proportion to their rates of glucose utilization and it changes together with local glucose consumption in response to altered local functional activity. These results demonstrate that the level of functional activity in the structural and functional components of the central nervous system regulates the local rate of energy metabolism, and local blood flow is adjusted to the local metabolic demand.

Animals↗
PubMed1993

Breast-conserving surgery and definitive radiation: a comparison between quadrantectomy and local excision with special focus on local-regional control and cosmesis.

PURPOSE: Breast-conserving surgery and definitive radiation as an alternative to mastectomy is a well-accepted practice. However, there is limited information addressing the extent of surgical resection. The purpose of this study is to compare the outcome of patients treated with local excision or quadrantectomy, followed by definitive radiation with particular emphasis on local-regional control and cosmetic results. METHODS AND MATERIALS: Between 1978 and 1989, 425 patients with Stage I and II breast cancer underwent conservative surgery followed by definitive radiation. Fifty-four patients had a local excision and 371 had a quadrantectomy. Median follow-up was 42 months. Axillary dissection (levels I/II) was performed in 317 patients, and of these 126 patients had positive axillary lymph nodes. Radiation consisted of 4500-5000 cGy to the breast with Co60 or 4 MV photons, plus a boost to the tumor site (356/425 patients) for a total dose of 6000-6500 cGy. Treatment of the regional lymph nodes was given to patients with undissected or inadequately dissected axillas and usually to patients with multiple positive lymph nodes. Of the patients with positive lymph nodes, 46% received systemic chemotherapy. RESULTS: The 5-year actuarial freedom from local-regional recurrence rates for patients treated with local excision and quadrantectomy followed by definitive radiation were 92% and 93%, respectively (p = 0.7). The 5-year actuarial survival rates for local excision and quadrantectomy were as follows: overall (83% and 82%; p = 0.7), cause-specific disease-free (74% and 71%; p = 0.9), and distant disease-free (82% and 76%, p = 0.4). Estimated 10-year results are also presented. Cosmetic analysis required a minimum follow-up of 5 years. In the local excision, 77% of the patients had excellent-good result, compared to 53% following quadrantectomy (p = 0.03). Excluding patients who received chemotherapy, the excellent-good scores were 76% and 57%, respectively (p = 0.1). The most unfavorable cosmetic results were associated with quadrantectomy followed by radiation with boost dose and chemotherapy, excellent-good in 22%. CONCLUSION: Conservative surgery consisting of local excision or quadrantectomy resulted in comparable local-regional control, overall, disease-free and distant disease-free survival, although cosmetic results were superior in the local excision group.

Adult↗
PubMed2000

Byr4 localizes to spindle-pole bodies in a cell cycle-regulated manner to control Cdc7 localization and septation in fission yeast.

Cytokinesis and septation in the fission yeast Schizosaccharomyces pombe are studied as a model for mammalian cell division. In fission yeast, septation is positively regulated by Spg1, a Ras family GTPase that localizes to spindle-pole bodies (SPBs) throughout the cell cycle. As cells enter mitosis, Spg1 accumulates in an active, GTP-bound form and binds the Cdc7 protein kinase to cause Cdc7 translocation to SPBs. Cdc7 disappears from one SPB in mid-anaphase and from the second SPB in late mitosis. Byr4 plus Cdc16 negatively regulate septation by forming a two-component GTPase-activating protein for Spg1. These results led us to hypothesize that Byr4 localization to SPBs regulated the nucleotide state of Spg1, due to its ability to form Spg1GAP activity with Cdc16 and thus the binding of Cdc7 to Spg1 at SPBs. To test this hypothesis, Byr4 localization was determined using indirect immunofluorescence. This analysis revealed that Byr4 was localized to SPBs that did not contain Cdc7. In byr4(-) mutants, Cdc7 localized to interphase SPBs and only symmetrically localized to mitotic SPBs. In contrast, Byr4 overexpression prevented Spg1 and Cdc7 localization to SPBs. These results suggest that Byr4 localization to SPBs maintains Spg1 in an inactive form, presumably by stimulating Spg1 GTPase activity with Cdc16, and that loss of Byr4 from mitotic SPBs increases the active fraction of Spg1 and thereby increases Spg1-Cdc7 binding. Byr4 localization to SPBs was decreased in spg1, cdc16, sid4, and cdc11 mutants as well as in several mutants that affect medial F-actin structures, suggesting that multiple pathways regulate Byr4 localization to SPBs.

Cell Cycle↗
PubMed2001

Senescence represses the nuclear localization of the serum response factor and differentiation regulates its nuclear localization with lineage specificity.

The differentiation of cultured 3T3T mesenchymal stem cells into adipocytes represses growth factor responsiveness by limiting the nuclear localization of the serum response factor (SRF) that binds to and activates the promoters of growth control genes that contain the serum response elements (SRE), such as junB and c-fos. The regulation of SRF nuclear localization by adipocyte differentiation is specific, because we show that adipocyte differentiation does not repress the nuclear localization of six other transacting factors. To determine if repression of growth factor responsiveness that occurs during senescence also represses the nuclear localization of SRF, we studied normal human WI-38 fibroblasts at low versus high population doublings. The results show that SRF localizes to the nucleus of proliferative cells whereas in senescent cells SRF can not be detected in the nucleus. This result is apparent in both immunofluorescence assays and in western blot analysis. We next evaluated the cellular distribution of SRF in selected human tissues to determine whether the loss of proliferative potential in vivo could have a different effect on SRF nuclear localization. We found that in cells of the small bowel mucosa, differentiation modulates SRF nuclear localization in an opposite manner. Minimal SRF expression and nuclear localization is evident in undifferentiated cells at the base of crypts whereas increased SRF expression and nuclear localization is evident in differentiated cells at the surface tip of the villus. These results together establish that regulation of SRF expression and nuclear localization is important in senescence and differentiation in a lineage specific manner.

Adipocytes↗
PubMed2004

Anurans from a local assemblage in central Brazil: linking local processes with macroecological patterns.

Macroecological variables of Anuran species found in a local assemblage from Central Brazil (Silvânia, Goiás State) were linked to population dyamics statistics of these species. Geographical range size (GRS), body size, and species' midpoints were the macroecological variables investigated for those species found in the local assemblage and for all other species (105 in the total) found in the Cerrado biome. For each species found in the local assemblage, data on abundance was obtained. Using this data, local population variability as expressed by the coefficient of variation was estimated. Distribution of means, medians, maximum, variances, and skewness (g1), for both GRS and body size, estimated in the local assemblage were compared, using null models, with the data extracted from the overall Cerrado species pool. The results indicated a clear macroecological relationship between GRS and body size and a decrease in local abundance when distance between the locality analyzed and species midpoint increased. According to null models, both body size and GRS values measured in the local assemblage can be considered a random sample from the regional species pool (Cerrado region). Finally, a three-dimensional analysis using body size, GRS, and local population estimates (abundance and variability), indicated that less abundant and more fluctuating species fell near the lower boundary of the polygonal relationship between GRS and body size. Thus, macroecological results linked with local data on population dynamics supported the minimum viable population model.

Animals↗
PubMed1981

The program implications of administrative relationships between local health departments and state and local government.

A typology of organizational arrangements between state and local public health agencies was used as a framework within which the organizational environment of the local health department was studied for its effects on program development and implementation by local public health departments. Data collected in a national sample of local health officers were used in measuring the effect of four different patterns of administrative relationships on the selected characteristics of local health department programs. Important differences were observed among the four organizational types with regard to constraints on programs and program priorities, and health officers' perceptions of the primary functions of local health departments and sources of local health department funding. These findings were then used as a baseline from which to consider the possible impact of recent federal health budgetary proposals (specifically, block grants) both on existing patterns of intergovernmental relations and on the funding and operation of local health department programs. It was determined that the most likely general development arising from these proposed changes in federal budgetary policy is that the administrative control of state health agencies over those at the local level is likely to be enhanced. Other likely developments include changes in the programs and priorities of local health departments related to reductions in overall funding levels for human services and forced competition for fewer dollars by an enlarged constituency.

Community Health Services↗
PubMed1980

Local cerebral energy metabolism: its relationship to local functional activity and blood flow.

The results of studies with the (14C)deoxyglucose technique unequivocally establish that local energy metabolism in cerebral tissues is, as in other tissues, closely coupled to local functional activity. Stimulation of local functional activity increases the local rate of glucose utilization; reduced functional activity depresses it. Local cerebral blood flow is normally distributed among the cerebral structures in almost exact proportion to their rates of glucose utilization and changes together with local glucose consumption in response to altered local functional activity. These results demonstrate that the level of functional activity in the structural and functional components of the central nervous syetem regulates the local rate of energy metabolism, and local blood flow is adjusted to the local metabolic demand.

Animals↗
PubMed1996

Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer.

PURPOSE: The aims of this prospective study were to evaluate the outcome and the possibility of breast conservation therapy for patients with locally advanced noninflammatory breast cancer after primary chemotherapy followed by external preoperative irradiation. METHODS AND MATERIALS: Between April 1982 and June 1990, 97 patients with locally advanced nonmetastatic and noninflammatory breast cancer were treated. The median follow-up was 93 months from the beginning of treatment. The induction treatment consisted of four courses of chemotherapy (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative irradiation (45 Gy to the breast and nodal areas). A fifth course of chemotherapy was given after irradiation therapy. Three different loco-regional approaches were proposed, depending on the tumoral response. In 37 patients (38%) with residual tumor larger than 3 cm in diameter or located behind the nipple or with bifocal tumors, mastectomy and axillary dissection were performed. Sixty other patients (62%) benefited from conservative treatment: 33 patients (34%) achieved complete remission and no surgery was done but additional radiation boost was given to the initial tumor bed; 27 patients (28%) who had a residual mass less than or equal to 3 cm in diameter were treated by wide excision and axillary dissection followed by a boost to the excision site. After completion of local therapy, all patients received a sixth course of chemotherapy. A maintenance adjuvant chemotherapy regimen without anthracycline was prescribed (12 monthly cycles). RESULTS: The 5-year actuarial loco-regional relapse rate was 16% after radiotherapy alone, 16% following wide excision and radiotherapy, and 5.4% following mastectomy. The 5-year loco-regional relapse rate was significantly higher after conservative local treatment (wide excision and radiotherapy, and radiotherapy alone) than after mastectomy (p= 0.04). After conservative local treatment, the 5-year breast conserving rate of patients with loco-regional disease-free status was 84%. For all patients included in this study, the 5-year breast-conserving rate of those who were loco-regional disease-free was 52%. In multivariate analysis, the possibility of breast conservative treatment was significantly related to the initial tumor size and age (more conservative treatment for tumor size < 6cm and age < 50 years). Five- and 10-year overall survival rates and disease-free survival rates were 80, 69, 73, and 61% respectively. Five- and 10-year overall survival rates were not influenced by the local treatment (conservative vs. nonconservative local treatment, p = 0.9). On the other hand, local failure significantly decreased the 5- and 10-year overall survival rates (p , 0.0001). In multivariate analysis, three factors had a significant impact on overall survival and disease-free survival: tumor response after induction chemotherapy, initial tumor size, and clinical stage. Arm lymphedema was noted in 12.5% (8 out of 64) of the patients treated with axillary dissection and in 3% (1 out of 33) without axillary dissection. Cosmetic results were satisfactory in 79% of patients after wide excision and radiotherapy and in 71% of patients treated by radiotherapy alone. CONCLUSIONS: Induction chemotherapy followed by preoperative irradiation may permit the selection of some patients with locally advanced breast cancer for conservative treatment. However, the impact of this treatment modality on long-term survival remains to be established.

Adult↗
PubMed2005

Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ.

The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of 90 women with local only first failure (n=85) or local-regional only first failure (n=5). The histology at the time of recurrence was invasive carcinoma for 53 patients (59%), non-invasive carcinoma for 34 patients (38%), angiosarcoma for one patient (1%), and unknown for two patients (2%). The median follow-up after salvage treatment was 5.5 years (mean=5.8 years; range=0.2-14.2 years). The 10-year rates of overall survival, cause-specific survival, and freedom from distant metastases after salvage treatment were 83%, 95%, and 91%, respectively. Adverse prognostic factors for the development of subsequent distant metastases after salvage treatment were invasive histology of the local recurrence and pathologically positive axillary lymph nodes. These results demonstrate that local and local-regional recurrences can be salvaged with high rates of survival and freedom from distant metastases. Close follow-up after initial breast conservation treatment with radiation is warranted for the early detection of potentially salvageable local and local-regional recurrences.

Adult↗
PubMed2006

Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer.

AIMS: To report the role of total pelvic exenteration in a series of locally advanced and recurrent rectal cancers. METHODS: In the period 1994-2004, TPE was performed in 35 of 296 patients with primary locally advanced and recurrent rectal cancer treated in the Daniel den Hoed Cancer Center; 23 of 176 with primary locally advanced and 12 of 120 with recurrent rectal cancer. All but one patient received pre-operative External Beam Radiation Therapy (EBRT). After 1997, Intra Operative Radiotherapy (IORT) was performed in case of a resection margin less than 2 mm. RESULTS: Overall major complication rates were not significantly different between patients with primary and recurrent rectal cancer (26% vs. 50%, p=0.94). The hospital mortality rate was 3%. The 5-year local control and overall survival of patients with primary locally advanced rectal cancer were 88% and 52%, respectively. In patients with recurrent rectal cancer 3-year local control and survival rates were 60% and 32%, respectively. An incomplete resection, preoperative pain and advanced Wanebo stage for recurrent cancer were negative prognostic factors for both local control and overall survival. CONCLUSION: TPE in primary locally advanced rectal cancer enables good local control and acceptable overall survival, thereby justifying the use of the procedure. Patients with recurrent rectal cancer showed a high rate of major complications, a high distant metastasis rate, and a poor overall survival.

Adult↗
PubMed1999

Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer.

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects. MATERIAL AND METHODS: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4 x 2.5 Gy/week to 50 Gy total dose (4-12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status. RESULTS: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed. CONCLUSION: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60% for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.

Adult↗
PubMed1992

Effect of body locale and addition of epinephrine on the duration of action of a local anesthetic agent.

STUDY OBJECTIVE: Little information exists relating body locale to the duration of action of local anesthetics. We tested the duration of action of a local anesthetic with and without epinephrine at different body locales. PARTICIPANTS: Twenty healthy volunteers aged 27 to 48 years (mean, 32.0 years). INTERVENTIONS: In the first of two experiments (L), 20 subjects had 1 mL buffered 1% lidocaine injected intradermally on the forehead, hand, forearm, and calf. In the second experiment (LE), ten subjects were injected at the same sites with lidocaine containing epinephrine. METHODS: Subjects ranked anesthesia by reaction to pinprick from 0 (complete) to 20 (none) on a scale with testing done every 15 (L) or 30 (LE) minutes and continued until no anesthetic effect was present. Duration of effective and of any anesthesia were times until score of more than 5 and of more than 19, respectively. Mean duration of anesthesia was compared by analysis of variance (between body areas) and paired two-tailed t-test (L vs LE). Significance was taken as P less than or equal to .05. RESULTS: Anesthesia was significantly briefer for the face than for all other body locales by both indexes of duration and for both plain lidocaine and lidocaine with epinephrine (P less than .001 to P less than .05). Anesthesia with epinephrine lasted significantly longer than with lidocaine alone at all body locales and for duration of both effective or any anesthesia (P = .0001 to P = .001). Based on 95% confidence interval limits, the duration of anesthesia at other body locales is predicted to be 1.3- to 3.2-fold that on the face. Confidence interval analysis indicated that addition of epinephrine to lidocaine increases the duration of anesthetic action by 1.3- to 13.0-fold that of lidocaine alone. CONCLUSION: The duration of action of local anesthesia is considerably shorter for the face than for other body areas. Epinephrine significantly increases the duration of action of lidocaine at all body locales.

Adult↗
PubMed2001

Urologic and sexual morbidity following multimodality treatment for locally advanced primary and locally recurrent rectal cancer.

AIMS: In the treatment of patients with locally advanced primary or locally recurrent rectal cancer much attention is given to the oncological aspects. In long-term survivors, urogenital morbidity can have a large effect on the quality of life. This study evaluates the functional outcome after multimodality treatment in these patient groups. PATIENTS AND METHODS: Between 1994 and August 1999, 55 patients with locally advanced primary and 66 patients with locally recurrent rectal cancer were treated with multimodality treatment: i.e. high-dose preoperative external beam radiation therapy, followed by extended surgery and intraoperative radiotherapy. The medical records of the 121 patients were reviewed. To assess long-term urogenital morbidity, all patients still alive, with a minimum follow-up of 4 months, were asked to fill out a questionnaire about their voiding and sexual function. Seventy-six of the 79 currently living patients (96%) returned the questionnaire (median FU 14 months, range 4-60). RESULTS: The questionnaire revealed identifiable voiding dysfunction as a new problem in 31% of the male and 58% of the female patients. In 42% of patients after locally advanced primary and 48% after locally recurrent rectal cancer treatment bladder dysfunction occurred. The preoperative ability to have an orgasm had disappeared in 50% of the male and 50% of the female patients, and in 45% of patients after locally advanced primary and in 57% after locally recurrent rectal cancer treatment. CONCLUSION: Multimodality treatment for locally advanced primary and recurrent rectal cancer results in acceptable urogenital dysfunction if weighed by the risk of uncontrolled tumour progression. Long-term voiding and sexual function is decreased in half of the patients. Preoperative counselling of these patients on treatment-related urogenital morbidity is important.

Adult↗
PubMed2006

ErbB receptor dimerization, localization, and co-localization in mouse lung type II epithelial cells.

ErbB receptors are crucial for embryonic neuronal and cardiac development. ErbB receptor ligands neuregulin (NRG) and epidermal growth factor (EGF) play a major role in the developing lung, specifically in mesenchymal induced fetal surfactant synthesis by type II epithelial cells. Different erbB receptor ligands cause diverse biologic effects by stimulating specific erbB-dimers. It is not known how dimerization, cellular localization, and co-localization of erbB dimers are regulated in type II epithelial cells. We hypothesized that erbB receptors have a distinct dimerization, localization, and co-localization pattern in type II cells. In mouse type II epithelial cells, which express all four erbB receptors, erbB1 and erbB4 were the preferred dimerization partners. These dimerization patterns were ligand independent. Confocal microscopy showed these transmembrane receptors exhibited a strong nuclear localization. In non-stimulated cells, both erbB1 and erbB2 were predominantly localized to the nucleus and less intensely to the cytoplasm. However, erbB1 was mainly found in the nucleoli, whereas erbB2 spared the nucleolar region. ErbB3 was exclusively located in the nucleoli. ErbB4 was diffusely located in nucleus and cytoplasm, and like erbB2 spared the nucleolar region. Short stimulation with either EGF or NRG led to a more pronounced nuclear staining for erbB1, erbB2, and erbB4. All four receptors co-localized with each other after stimulation, but with varying intensity. The two known stimulators of fetal surfactant synthesis, NRG and NRG-containing fibroblast conditioned medium, changed cellular localization of the dimerization partners erbB4 and erbB2 in a distinct fashion. We conclude that erbB receptors have a receptor-specific localization and dimerization pattern in type II epithelial cells.

Animals↗