Use of brachytherapy in management of locally recurrent rectal cancer

PURPOSE: Locally recurrent rectal cancer is associated with poor quality of life and has justified aggressive surgical and adjuvant approaches to control the disease. This study was designed to evaluate if the use of brachytherapy in association with wide surgical excision (debulking operation) can offer reasonable palliation for patients with locally recurrent rectal cancer. MATERIALS AND METHODS: Patients with biopsy-proven locally recurrent rectal cancer who were not candidates for intraoperative radiation therapy and who were previously considered as having unresectable tumors were included in the study and were followed-up from May 1981 to November 1990. All of them had undergone laparotomy and had either radical or debulking surgical resection performed. At the same time, brachytherapy was used with temporary or permanent implant of seeds of iridium-192 or iodine-125. RESULTS: Thirty patients were included. Patients ranged in age from 28 to 74 years, and 16 patients were female. No mortality was observed, and morbidity was low (small-bowel obstruction (1 patient), intestinal fistula (1 patient), and urinary fistula (1 patient). Histologic examination of the specimen showed gross residual disease in 67 percent of patients and microscopic disease in 25 percent of patients. Long-term follow-up was possible in 28 patients. Mean follow-up and local control were, respectively, 26.5 months and 37.5 percent for gross residual disease and 34 months and 66 percent for microscopic residual disease. Eighteen patients (64 percent) had locally recurrent rectal cancer under control at the time of the last follow-up, with seven patients (25 percent) having no evidence of local or distant recurrence. CONCLUSION: This is the first report of brachytherapy for locally recurrent rectal cancer. This appears to offer a therapeutic alternative to patients who are not candidates for intraoperative radiation therapy. Surgical morbidity and mortality are acceptable. Local control in 18 patients (64 percent) is comparable with intraoperative radiation therapy or more morbid surgical alternatives. Cancer-related deaths are most often related to disseminated disease, which suggests the need for systemic therapy in addition to brachytherapy.     

Platelets inhibit the induction of nitric oxide synthesis by interleukin-1 beta in vascular smooth muscle cells

We have investigated the role of platelets in regulating the hemostatic and vasomotor properties of vascular smooth muscle. Experiments were performed to examine the effect of the releasate from activated platelets on the production of nitric oxide from interleukin-1 beta (IL- 1 beta)-treated cultured rat aortic smooth muscle cells. Treatment of vascular smooth muscle cells with IL-1 beta resulted in significant accumulation of nitrite in the culture media and in marked elevation of intracellular cyclic guanosine monophosphate (GMP) levels. The releasate from collagen-aggregated platelets blocked the IL-1 beta- mediated production of nitrite and the accumulation of cyclic GMP in smooth muscle cells in a platelet number-dependent manner. In functional assays, the perfusates from columns containing IL-1 beta- treated smooth muscle cells relaxed detector blood vessels without endothelium and the addition of IL-1 beta-treated smooth muscle cells to suspensions of platelets inhibited their thrombin-induced aggregation. The simultaneous treatment of smooth muscle cells with IL- 1 beta and the platelet releasate abolished both the vasorelaxing activities of the perfusates and the inhibition of platelet aggregation. Platelet releasates treated with a neutralizing antibody to platelet-derived growth factor (PDGF) failed to block IL-1 beta- induced nitric oxide production by the smooth muscle cells, as measured by both biochemical and functional assays. The platelet releasate from a patient with gray platelet syndrome likewise failed to block IL-1 beta-induced nitrite release by smooth muscle cells. These results demonstrate that platelets downregulate the production of nitric oxide by IL-1 beta-treated vascular smooth muscle cells through the release of PDGF. This effect may represent a novel mechanism by which platelets regulate vasomotor tone and thrombus formation at sites of vascular injury.     

Development of large numbers of mast cells at sites of idiopathic chronic dermatitis in genetically mast cell-deficient WBB6F1-W/Wv mice

The normal skin and other tissues of adult mast cell-deficient WBB6F1- W/Wv or WCB6F1-Sl/Sld mice contain less than 1.0% the number of mast cells present in the corresponding tissues of the congenic normal (+/+) mice. As a result, genetically mast cell-deficient WBB6F1-W/Wv or WCB6F1-Sl/Sld mice are widely used for studies of mast cell differentiation and function. We found that mast cells developed at sites of idiopathic chronic dermatitis in WBB6F1-W/Wv mice and that the number of mast cells present in the skin of WBB6F1-W/Wv mice was proportional to the severity of the dermatitis (in ear skin, there were 33 +/- 4 mast cells/mm2 of dermis at sites of severe dermatitis v 9 +/- 3 at sites of mild dermatitis, 0.8 +/- 0.3 in skin without dermatitis, and 100 +/- 7 in the normal skin of congenic WBB6F1-+/+ mice; in back skin, the corresponding values were 2.0 +/- 0.6, 1.1 +/- 0.9, 0.025 +/- 0.025, and 26.2 +/- 3.2). The development of mast cells was a local, not systemic, consequence of the dermatitis. Thus, WBB6F1-W/Wv mice with severe dermatitis lacked mast cells in skin not showing signs of dermatitis and also in the peritoneal cavity, stomach, cecum, and tongue. Idiopathic chronic dermatitis was not associated with the local development of mast cells in WCB6F1-Sl/Sld mice, a mutant whose mast cell deficiency is due to a mechanism distinct from that of WBB6F1-W/Wv mice. These findings may have implications for understanding the nature of the mast cell deficiency in WBB6F1-W/Wv and WCB6F1-Sl/Sld mice and for the use of these mutants to analyze mast cell differentiation and function.     

Selecting the best and brightest: A comparison of residency match processes in the United States and Canada

BACKGROUND:

Selecting candidates for plastic surgery residency training remains a challenge. In the United States, academic measures (United States Medical Licensing Exam Step I scores, medical school class rank and publications) are used as primary criteria for candidate selection for residency. In contrast, Canadian medical education de-emphasizes academic measures by using a pass-fail grading system. As a result, choosing residents from many qualified applicants may pose a challenge for Canadian programs without objective measures of academic success.

METHODS:

A 25-question online survey was distributed to program directors of Canadian plastic surgery residency-training programs. Program directors commented on number of yearly residents and applicants; application sections (ranked in importance using a Likert scale); interview invitation and rank-order list determination; and their satisfaction with the selection process.

RESULTS:

Ten Canadian plastic surgery program directors responded (90.9% response rate). The most important application components determining invitation to interview were letters of reference from a plastic surgeon (mean importance of 5.0 on the Likert scale), clinical electives in plastic surgery (mean 4.6) and electives with their program (mean 4.5). Applicants invited for interview were assessed on the quality of their responses to questions, maturity and personality. The majority of program directors agreed that a clinical elective with their program was important for consideration on their rank-order list. Program directors were neutral on their satisfaction with the selection process.

CONCLUSION:

Canadian plastic surgery residency programs emphasize clinical electives with their program and letters of reference from colleagues when selecting applicants for interviews. In contrast to their American counterparts, Canadian program directors rely on clinical interactions with prospective residents in the absence of objective academic measures.     

Immunoglobulin G from patients with heparin-induced thrombocytopenia binds to a complex of heparin and platelet factor 4

Heparin-induced thrombocytopenia (HIT) is an important complication of heparin therapy. Although there is general agreement that platelet activation in vitro by the HIT IgG is mediated by the platelet Fc receptor, the interaction among the antibody, heparin, and platelet membrane components is uncertain and debated. In this report, we describe studies designed to address these interactions. We found, as others have noted, that a variety of other sulfated polysaccharides could substitute for heparin in the reaction. Using polysaccharides selected for both size and charge, we found that reactivity depended on two independent factors: a certain minimum degree of sulfation per saccharide unit and a certain minimum size. Hence, highly sulfated but small (< 1,000 daltons) polysaccharides were not reactive nor were large but poorly sulfated polysaccharides. The ability of HIT IgG to recognize heparin by itself was tested by Ouchterlony gel diffusion, ammonium sulfate and polyethylene glycol precipitation, and equilibrium dialysis. No technique demonstrated reactivity. However, when platelet releasate was added to heparin and HIT IgG, a 50-fold increase in binding of radio-labeled heparin to HIT IgG was observed. The releasate was then depleted of proteins capable of binding to heparin by immunoaffinity chromatography. Only platelet factor 4-immunodepleted releasate lost its reactivity with HIT IgG and heparin. Finally, to determine whether the reaction occurred on the surface of platelets or in the fluid phase, washed platelets were incubated with HIT IgG or heparin and after a wash step, heparin or HIT IgG was added, respectively. Reactivity was only noted when platelets were preincubated with heparin. Consistent with these observations was the demonstration of the presence of PF4 on platelets using flow cytometry. These studies indicate that heparin and other large, highly sulfated polysaccharides bind to PF4 to form a reactive antigen on the platelet surface. HIT IgG then binds to this complex with activation of platelets through the platelet Fc receptors.     

Myocardial tissue iron delocalization and evidence for lipid peroxidation after two hours of ischemia

Ischemic tissue injury has been proposed to be in part due to oxygen-radical-mediated lipid peroxidation. In vitro studies of such reactions show that they are thermodynamically unfavorable unless catalyzed by transitional metals such as iron in low molecular weight species (LMWS iron), ie, the iron-ADP complex. This study tests for iron delocalization into a LMWS pool during myocardial ischemia and for increased tissue malondialdehyde (MDA), a product of lipid peroxidation. Anesthesia was induced in eight dogs (weighing 20 to 30 kg) with ketamine and maintained by ventilation with 1% halothane. The left anterior descending coronary artery was ligated in four animals, and the circumflex coronary artery was ligated in the other four. Two hours after ligation, the animals were sacrificed by a central venous injection of KCl. Tissue samples were immediately taken from the ischemic zone and from the corresponding nonischemic zone. MDA was determined by the thiobarbituric acid assay. LMWS iron was determined on a tissue ultrafiltrate by the o-phenanthroline assay. Statistical data analysis used the matched-pair two-tailed t test. LMWS iron was 18.3 nM/100 mg in ischemic tissue versus 13.1 nM/100 mg in nonischemic tissue (t = 4.14; P less than .01). MDA was 0.91 nM/100 mg in ischemic tissue versus 0.83 nM/100 mg in nonischemic tissue (t = 7.27; P less than .005). We conclude that there is a significant increase in tissue LMWS iron and in MDA after two hours of regional myocardial ischemia. This iron might be the catalyst for maturation of tissue injury during reperfusion as observed by other investigators.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute compartment syndrome of the upper extremity in children: diagnosis, management, and outcomes

Purpose

Acute compartment syndrome (ACS) of the upper extremity is a rare but serious condition. The purpose of this study was to determine the etiology, diagnosis, treatment, and outcome of ACS of the upper extremity in a pediatric population.

Methods

We performed a retrospective chart review of all patients who underwent a decompressive fasciotomy for ACS of the upper extremity. Data collected included demographics, injury details, presenting symptoms, compartment measurements, time to diagnosis, time to treatment, and outcomes at the latest follow-up.

Results

Twenty-three children underwent fasciotomies for ACS of the forearm (15) and hand (8), at an average age of 9.3 years (range 0–17.8 years). The most common etiologies were fracture (13) and intravenous (IV) infiltration (3). The most common presenting symptoms were pain (83 %) and swelling (65 %). Compartment pressures were measured in 17/23 patients, and all but two patients had at least one compartment with a pressure >30 mmHg. The final two patients were diagnosed and treated for ACS based on clinical signs and symptoms. The average time from injury to fasciotomy was 32.8 h (3.7–158.0 h). Long-term outcome was excellent for 17 patients (74 %) and fair for 5 (22 %), based on the presence of loss of motor function, stiffness, or decreased sensation. One patient with brachial plexus injury and poor baseline function was excluded from functional outcome scoring. There was no association between the time from diagnosis to fasciotomy and functional outcome at the final follow-up (p = 1.000).

Conclusions

Although ACS of the upper extremity in children is often associated with a long delay between injury and fasciotomy, most children still achieve excellent outcomes. The majority of patients presented with pain and at least one additional symptom, but treatment was often delayed, implying that ACS of the upper extremity in children is a difficult diagnosis to establish and may be associated with a prolonged clinical time course.     

Ontogeny of the Therapeutic Alliance in Borderline Patients

The development of the therapeutic alliance is explored in a prospective study of 33 borderline personality disorder patients. Assessments of the alliance were made by both the patients and their therapists using the Penn Helping Alliance Questionnaire at six weeks, six months, and then annually for up to five years.The major findings were: (1) The alliance was rated highly by both patients and therapists throughout treatment; (2) the alliance showed steady and significant improvement over time (and no significant deterioration at any point); (3) patients and therapists corresponded closely in their assessments; (4) therapists rated the alliance higher than did patients at three and four years; (5) therapist ratings of the alliance at six weeks was predictive of subsequent dropping out; but (6) early alliance scores were not strongly related to subsequent level of change. These results frame issues for future research in this area.Die Entwicklung der therapeutischen Allianz wurde in einer prospektiven Studie bei 33 Patienten mit Borderline-Persönlichkeitsstörungen überprüft. Die Einschätzungen der Allianz wurden sowohl von den Patienten als auch von ihren Therapeuten mit Hilfe des Penn Helping Alliance Fragbogens nach sechs Wochen, sechs Monaten und dann jährlich über den Zeitraum von fünf Jahren vorgenommen.Die Ergebnisse der Studie sind: 1) Die Allianz wurde sowohl von den Patienten als auch von den Therapeuten über die gesamte Behandlung hinweg hoch eingeschätzt; 2) Die Allianz verbesserte sich stetig und signifikant innerhalb des Behandlung-szeitrwams und wies keine signifkante Verschlechterung an irgendeiner Stelle des Prozesses auf; 3) Patienten und Therapeuten stimmten in ihren Einschätzungen weitgehend überein; 4) Therapeuten schätzten die Allianz im dritten und vierten Jahr höher ein als die Patienten; 5) Die Einschätzung der therapeutischen Allianz nach sechs Wochen durch den Therapeuten kann spétere Therapieabbrüche vorhersagen, aber 6) die frühen Allianzwerte waren nicht sehr ausgeprägt bezogen auf spätere Veränderungswerte. Die Ergebnisse stecken den Rahmen für zukünftige Studien in diesem Bereich ab.Le développement de l'alliance thérapeutique est exploré dans une étude prospective sur 33 patients avec trouble de la personnalité borderline. Des évaluations de l'alliance ont été faites par les patients et leur thérapeute à l'aide du Questionnaire Penn Helping Alliance, à six semaines, six mois et ensuite annuellement pendant cinq ans.Les découvertes majeures ont été: 1) L'alliance a été à évaluée ‘forte’ à la fois par les patients et les thérapeutes pendant le traitement; 2) L'alliance a montré une amélioration stable et significative à travers le temps (et à aucun moment il n'y a eu de détérioration significative); 3) Les évaluations des patients et des thérapeutes correspondaient fortement; 4) Les thérapeutes ont évalués l'alliance plus forte que l'ont fait les patients aprés trois et quat ans; 5) Les évaluations de l'alliance par les thérapeutes étaient prédictives d'un subséquent désistement; mais 6) Les scores de l'alliance précoce n'étaient pas fortement liés à un subséquent niveau de changement. Ces résultats formulent des points intéressants de discussion pour de futures recherches dans ce domaine.