VLA(3)/integrin expression in breast carcinomas evaluated by automated and quantitative immunohistochemistry

VLA, expression was immunohistochemically investigated in 145 breast carcinomas. Frozen tissue sections were probed with monoclonal anti-VLA, using automated (Ventana ES 320 system) and quantitative (SAMBA 2005 image processor) immunoperoxidase. A positive anti-VLA, immunoreaction was observed in 86 tumors (23.5%) within epithelial cells of carcinomas. The positive surface in tumors varied from 3% to 38% (mean = 13.8%, SD=11.5) and was independent of the tumor size, grade, type and aneuploidy, and of nodal status. VLA(2) was significantly correlated with VCAM (p<0.01), VLA(2) (p<0.01), E cadherin (p=0.025), and CD44 v (p<0.01), and an inverse relationship was observed with Ki67/MIB 1 (p=0.0024) and P-53 (p=0.034). In contrast VLA, expression proved to be independent of Bcl-2, c-erbB-2, cathepsin D, tenascin, CD31, ELAM, RE, RP, PS2 immunohistochemical expression. The results suggest that VLA, expression in tumors is related to the regulation of other adhesion molecules involved in the metastasis process, but the prognostic significance and clinical relevance of VLA, immunodetection in breast carcinomas remain to be demonstrated.     

Continent perineal colostomy by transposition of gracilis muscles

We herein present a study conducted on 14 patients presenting cancer of the lower rectum or of the anal canal (10 adenocarcinomas and 4 squamous-cell carcinomas) and submitted to the Miles abdominal perineal resection in which a new perineal sphincter was constructed. PURPOSE: The aim of this study was to evaluate the efficacy of this new perineal sphincter constructed by transposing the gracilis muscles around an orthotopic colostomy in the attempt to avoid a permanent abdominal colostomy. METHODS: In all cases both gracilis muscles were employed. The right one was placed along the posterior wall of the pelvis and fixed to the controlateral ischiatic tuberosity, creating a sling comparable to the levator ani muscles. The left gracilis was passed around the colon and attached to the ipsilateral or controlateral tuberosity according to its length, reconstructing a muscular ring. The entire procedure was performed in one step in nine cases and in more steps in the remaining five. RESULTS: Of the 14 operated patients, 2 died of vascular disease and 1 developed necrosis of the colonic stump which required reconversion to an abdominal colostomy. Of the remaining 11 patients available for long-term evaluations, 8 showed adequate stool control. The remaining three manifested an incomplete level of continence. During the three-year follow-up period, all patients were evaluated by clinical examination, defecography, endoluminal ultrasonography, nuclear magnetic resonance, CT scan, and endoluminal manometry. CONCLUSION: This neosphincter realizes an elastic stenosis responsible for an efficient level of continence. Best results are observed in the young and educated patients submitted to surgery in two steps. Contraindications to this surgery seem to be advanced cancer, old age, and obesity.     

Microscopic endoluminal tumorectomy

PURPOSE: We herein report our experience with transanal endoscopic microsurgery. The new technique combines an endoscopic view and access of the rectum under gas insufflationviaa stereoscopic telescope with all conventional surgical maneuvers such as tissue preparation, coagulation and control of bleeding, irrigation, suction, and, finally, suturing of the parietal defect. METHODS: The main indication for transanal endoscopic microsurgery is the removal of broad-based sessile polyps and excision of early rectal cancers. We performed local excision of pT2, G1-2 adenocarcinomas and excision of advanced rectal cancer in high-risk patients. The reported series includes 35 consecutive patients, who have been enrolled in a prospective clinical trial. Five patients were excluded for different reasons. The patients were submitted to 29 total wall excisions with or without perirectal fat and one mucosectomy. RESULTS: Postoperative histologic examination showed 9 adenomas and 21 adenocarcinomas. Morbidity included 2 (5.6 percent) perioperative and 2 (5.6 percent) late complications. There was no operative mortality and the mean postoperative hospital course was six days. All patients are in follow-up observation with a mean time of 10.3 months. In the group of adenomas and adenocarcinomas, we did not observe local recurrence. CONCLUSIONS: Considering our experience with the overall results reported by other authors, we believe that transanal endoscopic microsurgery is the procedure of choice for the treatment of rectal polyps and early rectal cancers provided strict patient selection criteria are met.     

Admission,recruitment, and retention

As the country strives to produce larger numbers of generalist physicians, considerable controversy has arisen over whether or not generalist applicants can be identified, recruited, and influenced to keep a generalist-oriented commitment throughout medical training. The authors present new and existing data to show that: 1) preadmission (BA/MD or post-baccalaureate) programs can help to identify generalist-oriented students; 2) characteristics determinedat admission to medical school are predictive of future generalist career choice; 3) current inpatient-oriented training programs strongly push students away from a primary care career; 4) women are more likely than men to choose generalist careers, primarily because of those careers’ interpersonal orientation; and 5) residency training programs are able to select applicants likely to become generalists. Therefore, to produce more generalists, attempts should be made to encourage generalist-oriented students to enter medical schools and to revise curricula to focus on outpatient settings in which students can establish effective and satisfying relationships with patients. These strategies are most likely to be successful if enacted within the context of governmental and medical school-based changes that allow for more reimbursement and respect for the generalist disciplines.     

Guinea-pig spinal-cord as a model for the study of late radiation-injury and repair

The risk of normal tissue damage imposes severe limitations on the radiotherapy of malignant tumours. The aim of this study was to examine the morphology of late radiation injury with special reference to microvasculature in the irradiated guinea pig spinal cord. Gamma radiation from a cobalt-60 source was used to irradiate the lumbar region of guinea pigs. A total dose of up to 94.5 Gy was given using 4.5 Gy fractions. Twenty such guinea pigs which survived more than 2 years post-irradiation were deeply anaesthetized and Mercox resin was perfused through the thoracic aorta. Ten minutes following perfusion, irradiated segments of the spinal cords were removed and either fixed in formalin for histology and morphometry or corroded in KOH for microvascular cast preparation. The latter were observed under the scanning electron microscope. All irradiated specimens showed multifocal white matter vacuolation. None of these spaces communicated with blood vessels. No such vacuolation was observed in grey matter. Glial cell counts in the irradiated white matter were reduced. Microvascular morphometry revealed 3.30% of the area was occupied by vasculature in the non-irradiated white matter. The corresponding value for irradiated white matter was 2.38% (p=0.003). No difference in the vascular area was noted in the non-irradiated grey matter (9.75%) and irradiated grey matter (10.36%; p=0.36) Microvascular casts did not reveal telangiectasia. However, irradiated specimens showed focal avascular regions. This was consistent with the light microscopic observation of focal degeneration and necrosis of irradiated white matter. These results suggest that late radiation injury in guinea pigs results primarily from damage to glial elements and the microvasculature is secondarily affected.     

Treatment of systemic and renal-limited vasculitic disorders with pooled human intravenous immune globulin

Idiopathic crescentic glomerulonephritis is characterized by an absence of immunohistological evidence of immune deposits, often with evidence of segmental glomerular necrosis. Such pauciimmune crescentic glomerulonephritis is the most common renal manifestation seen in patients with Wegener's granulomatosis, polyarteritis nodosa, and glomerulonephritis associated with other systemic vasculitic disorders (i.e., Churg-Strauss syndrome). Recently, the idiopathic crescentic glomerulonephritides, either in renal-limited form or in association with other systemic vasculitic disorders, were found to have in common a serologic marker, antineutrophil cytoplasmic autoantibodies. These cytoplasmic and perinuclear antineutrophil cytoplasmic autoantibodies are specific for constituents of neutrophil primary granules and monocyte lysosomes. As serologic markers for vasculitic disorders, they are also felt to be directly involved in the pathogenesis of necrotizing vascular injury.In vitro, both perinuclear and cytoplasmic antineutrophil cytoplasmic autoantibodies are capable of causing cytokineprimed neutrophils to undergo degranulation and respiratory burst, releasing toxic oxygen species and lytic enzymes. Antiidiotype antibodies which inhibit antineutrophil cytoplasmic autoantibodiesin vitro, in a V region-dependent manner, are found in pooled humanγ-globulin preparations. Intravenous immune globulin infusionsin vivo have produced dramatic improvements in the necrotizing vascular injury produced by antineutrophil cytoplasmic autoantibodies, and a rapid reduction in these autoantibody levels is seen post-intravenous immune globulin infusion in most patients. The proposed mechanisms of action of intravenous immune globulin in vasculitic disorders include Fc-dependent mechanisms, and F(ab′)₂-dependent mechanisms are likely important. Intravenous immune globulin infusions appear to have an important place in the management of the necrotizing vascular injury. Blinded, randomized, placebo-controlled trials will be necessary to establish definitively intravenous immune globulin as a therapeutic option in vasculitic disorders.     

Correlation of quantitative measures with the modified Ashworth scale in the assessment of plantar flexor spasticity in patients with traumatic brain injury

This study of plantar flexor spasticity describes relationships among a traditional qualitative spasticity scale, three potential quantitative spasticity measures and a measure of voluntary ankle muscle function. Thirty-four volunteer adult patients with traumatic brain injuries participated. There were 28 males and 6 females; the mean age was 30.3 years. A battery of five randomly sequenced tests was performed for each subject on one ankle. Tests were: modified Ashworth scale (MAS) scoring; H-reflex testing with and without Achilles tendon vibration; H-reflex testing with and without dorsiflexor contraction; reflex threshold angle and timed toe tapping (TTT). Twenty-six subjects returned to have the second ankle tested, resulting in 60 ankles for the analyses. Spearman's coefficients for correlation of quantitative spasticity measures with MAS scores ranged from 0.39 to 0.49 with associated probabilities 0.002. Pearson coefficients for correlation of quantitative spasticity measures with TTT scores were lower but also significant (P 0.07). Multiple correlation for the set of quantitative measures yieldedR = 0.614 (P < 0.001) with MAS scores andR = 0.365 (P = 0.045) with TTT scores. These findings reveal statistically significant relationships of low to moderate strength among potential quantitative spasticity measures, a traditional qualitative spasticity scale and a simple measure of voluntary ankle muscle function. Understanding these relationships is an essential part of the ongoing search for quantitative spasticity measures.The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.     

Mivacurium-induced neuromuscular blockade during sevoflurane and halothane anaesthesia in children

The neuromuscular blocking effects of mivacurium during sevoflurane or halothane anaesthesia was studied in 38 paediatric patients aged 1–12 yr. All received premedication with midazolam, 0.5 mg · kg⁻¹ po and an inhalational induction with up to 3 MAC of either agent in 70% N₂O and O₂. The ulnar nerve was stimulated at the wrist by a train-of-four stimulus every ten seconds and the force of adduction of the thumb recorded with a Myotrace force transducer. Anaesthesia was maintained with a one MAC end-tidal equivalent of either volatile agent for five minutes before patients received mivacurium (0.2 mg · kg⁻¹) iv. The onset of maximal blockade occurred in 2.4 ± 1.26 (mean ± SD) min with halothane and 1.8 ± 0.54 min with sevoflurane (NS). Four patients failed to achieve 100% block (3 halothane, 1 sevoflurane). The times from injection to 5, 75, and 95% recovery during sevoflurane (9.8 ± 2.6, 19.5 ± 4.4, and 24.2 ± 4.8 min) were greater than during halothane anaesthesia (7.2 ± 2.2, 15.0 ± 4.0, 19.2 ± 4.9 min, respectively (P < 0.005). All patients demonstrated complete spontaneous recovery of neuromuscular function (T₁ > 95%, T₄/T₁ > 75%) during the surgery which lasted 24–63 min. All patients showed clinical signs of full recovery of neuromuscular blockade (i.e., headlift, gag, or cough). Pharmacological reversal was not required. It is concluded that following a single intubating dose of mivacurium, the time to maximum relaxation was not different during halothane and sevoflurane anaesthesia; recovery times to 5, 75 and 95% twitch height were longer during sevoflurane anaesthesia and neuromuscular reversal was not necessary. L’activité neurobloquante du mivacurium pendant l’anesthésie au sévoflurane ou à l’halothane fait l’objet de cette étude réalisée chez 38 enfants de 1 à 12 ans. Tous ont été prémédiqués au midazolam 0,5 mg · kg⁻¹ et l’anesthésie est induite avec un agent volatil jusqu’à MAC 3 de l’un des agents dans du N₂O à 70%. Le nerf cubital était stimulé au poignet au train de quatre aux dix seconds et la force de l’adduction du pouce mesurée avec un transducteur de force Myotrace. L’anesthésie était entretenue avec l’équivalent MAC I d’un des deux agents volatils pendant cinq minutes avant l’administration de mivacurium (0,2 mg · kg⁻¹). Le début du bloc maximum est survenu dans 2,4 ± 1,26 (moyenne ± SD) min avec l’halothane et 1,8 ± 0,54 min avec le sévoflurane (NS). Quatre patients n’ont pas été bloqués à 100% (trois avec l’halothane, un avec le sévoflurane). L’intervalle séparant l’injection à 5; 75, et 95% de la récupération pendant l’anesthésie au sévoflurane (9,8 ± 2,6, 19,5 ± 4,4 et 24,2 ± 4,8 min) a été plus long que pendant l’anesthésie à l’halothane (7,2 ± 2,2, 15,0 ± 4,0, 19,2 ± 4,9 min, respectivement (P < 0,005). An moniteur, chez tous les patients, la fonction neuromusculaire a récupéré spontanément (T₁ > 95%, T₄/T₁ > 75%) au cours de la chirurgie qui a duré de 24–63 min. Tous les patients montraient aussi les signes cliniques d’une récupération complète (par ex., levée de la tête, réflexe pharyngé ou toux). Aucun antagoniste pharmacologique n’a été requis. Il est conclu que le délai jusqu’à la relaxation maximum après une seule dose d’intubation de mivacurium ne diffère pas entre l’anesthésie à l’halothane et l’anesthésie au sévoflurane; les délais de retour à 5, 75 et 95% de la hauteur du twitch sont plus longs pendant l’anesthésie au sévoflurane et il n’est pas nécessaire d’antagoniser le bloc neuromusculaire.

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Supported in part by a grant from Abbott Laboratories, Chicago, Illinois.     

The Burden of Obesity and Its Sequelae

Obesity [body mass index (BMI) ≥30 kg/m²] is common in many parts of the world, especially in the established market economies, formerly socialist economies of Europe and Latin America and the Caribbean, as well as the Middle Eastern Crescent. Worldwide, as many as 250 million people may be obese (7% of the adult population) and 2 to 3 times as many may be considered overweight (BMI 25 to 30 kg/m²). The prevalence of obesity seems to be increasing in most parts of the world, even in areas where obesity used to be rare.A waist circumference greater than 102cm in men and 88cm in women may be a more sensible classification than BMI to identify individuals who are at increased health risk because of obesity, but information on this point is still scarce.Increased fatness measured by a high BMI, large waist circumference or high waist/hip circumference ratio is associated with many chronic diseases as well as poor physical functioning. These all contribute to the costs associated with excess bodyweight. The economic costs of obesity can be broken down into 3 levels Direct costs: costs to the community related to the diversion of resources to the diagnosis and treatment of diseases directly related to obesity as well as the treatment of obesity itself. These costs have been estimated to account for 2 to 8% of total healthcare costs of various countries. Indirect (or societal) costs: these costs are related to the loss of productivity caused by absenteeism and premature death and disability pensions. There is a lack of good economic analysis in this area, although research from Sweden, Finland and The Netherlands has clearly shown that obesity is associated with increased sick leave and the need for disability pensions. Personal costs: obese individuals may earn less than their lean counterparts because of job discrimination (related to the stigma associated with obesity or because of diseases and disabilities caused by obesity). Many insurance companies (particularly life insurance) charge higher premiums with increasing degrees of overweight.In conclusion, there is much indirect information that obesity and overweight are important and growing public health concerns that contribute substantially to healthcare-related costs. Effective strategies for the prevention and management of obesity are needed.