Cognitions, coping and social environment predict adjustment to phantom limb pain.

Biopsychosocial models of chronic pain hypothesize a role for psychological and environmental factors in adjustment to chronic pain. To test the utility of such models for understanding phantom limb pain, 61 persons with recent amputations were administered measures of average phantom limb pain intensity, pain interference, depression, pain coping use, pain cognitions and appraisals, and social environmental variables 1 month post-amputation, and the measures of pain intensity, pain interference, and depression again 5 months later. Multiple regression analyses showed that the psychosocial predictors made a statistically significant contribution to the concurrent prediction of average phantom limb pain, pain interference, and depression at the initial assessment, and a significant contribution to the prediction of subsequent change in pain interference and depression over the course of 5 months. The results support the utility of studying phantom limb pain from a biopsychosocial perspective, and identify specific biopsychosocial factors (e.g., catastrophizing cognitions, social support, solicitous responses from family members, and resting as a coping response) that may play an important role in adjustment to phantom limb pain.     

Effectiveness of methyl-GAG (methylglyoxal-bis[guanylhydrazone]) in patients with advanced malignant lymphoma

We treated 51 patients with advanced malignant lymphoma refractory to conventional therapy with methyl-glyoxal-bis(guanylhydrazone) (methyl- GAG) at doses ranging from 400 to 800 mg/sq m. Therapy was started on a weekly schedule and was switched to every other week in responding patients at the onset of toxicity. Partial responses were observed in 6 of 13 evaluable patients with Hodgkin's disease (46%), 5 of 10 patients with diffuse poorly differentiated lymphocytic lymphoma (50%), 2 of 4 patients with nodular poorly differentiated lymphocytic lymphoma (50%), and 3 of 13 patients with diffuse histiocytic lymphoma (23%). Two of six patients with mycosis fungoides showed objective improvement in cutaneous disease. Toxicity was generally mild and included muscular weakness, myalgia, mucositis, and diarrhea; two patients developed bronchospasm following drug infusions. We conclude that methyl-GAG has major antitumor activity when administered on this schedule to patients with advanced malignant lymphoma. The low degree of toxicity, unique mechanism of action, and minimal myelosuppressive effects suggest that methyl-GAG will prove useful in future trials of combination chemotherapy regimens for the treatment of lymphoma.     

The effects of age and peripheral vascular disease on the circulatory and mechanical response of skin to loading

The skin and subcutaneous soft tissues of amputation residual limbs are required to withstand externally applied loads of greater magnitude than similar tissues of the intact lower limb. Increased age and poor circulatory status may contribute to the increased risk of tissue injury seen in this population. This study evaluates the effects of age and circulatory status as risk factors for skin injury resulting from externally applied forces. Twelve young control (YC), six elderly control (OC) and 11 subjects with peripheral vascular disease (PVD) were studied. After base-line ankle arm index (AAI) measurements, TcPO2 electrodes were applied 10 cm below the knee over the medial surface of the tibia and the muscle belly of tibialis anterior. TcPO2 measurements and tissue displacements were obtained under the influence of incremented, normally oriented, external loads. The sensitivity of the tissues to applied loads was determined by calculating the load at which the TcPO2 reached zero. The stiffness of the tissues (displacement/load) was calculated under high (greater than 40 mm Hg) and low (less than 20 mm Hg) loading conditions. No difference was noted in tissue sensitivity to applied loads between the OC and YC populations. The TcPO2 decreased to zero in the PVD population at significantly lower applied loads than both the OC and YC populations. The tissue stiffness of the PVD and the OC populations over bone was greater than the YC population, but no significant differences were noted between the PVD and the OC populations. In summary, increased age does not result in a greater tissue sensitivity to externally applied loads, in spite of the demonstrated increased tissue stiffness.(ABSTRACT TRUNCATED AT 250 WORDS)     

Psoriasis under the microscope

Histopathology is a major diagnostic tool in dermatology, particularly in psoriasiform diseases. Morphological studies showed that the initial event in psoriatic lesions is perivascular infiltrate, followed by dilatation of superficial papillary vessels. Proliferation of keratinocytes and neutrophil exocytosis are secondary events. Fully developed psoriasis has a very characteristic pattern, which includes elongation of rete ridges leading to regular acanthosis, oedema of the papillary dermis associated with tortuous dilated vessels, thinning of suprapapillar area, decreased thickness of granular layer, and exocytosis of neutrophils in the spinous layer (Kogoj's pustule) or in the cornified parakeratotic layer (Munro microabscesses). Pustular psoriasis is characterized by large or confluent intra‐epidermal multilocular pustules. Whatever the clinical variant of psoriasis, common morphological signs suggest that it is basically a unique pathological process, with many possible presentations according to various factors such as age, size and localization of lesions, or therapy. Similar microscopic elementary lesions indicate that Hallopeau's acrodermatitis continua, Reiter's disease and geographical tongue are variants of psoriasis. Because of the many faces of the disease, psoriasis can resemble many other squamous or pustular disorders. Differential diagnosis by microscopic analysis is based on pattern analysis, PAS (Periodic Acid Schiff) staining to rule out fungal infection, and immunohistochemistry to characterize lymphocytic infiltrate. Psoriasis is one of the most common inflammatory skin diseases. In its characteristic presentation, psoriasis comprises well‐circumscribed red scaly papules and plaques. In this form, the disease is generally easy to identify, especially when the elbows, knees and scalp are affected. Nevertheless, the term ‘psoriasis’ includes more clinical variants than any other inflammatory dermatosis: psoriasis vulgaris vs. pustular, localized vs. generalized, topographic variants, mucous membranes involvement, hair and nail lesions. Although some of these conditions might be extremely different from psoriasis vulgaris, common pathological findings can be identified in all of them. Microscopic analysis of psoriatic lesions may therefore help clinicians to make the diagnosis and to understand that, whatever the clinical presentation, signs and symptoms are mainly due to a unique pathological process.     

Inhibition of endotoxin-induced activation of the coagulation and fibrinolytic pathways using a recombinant endotoxin-binding protein (rBPI23)

A recombinant endotoxin-neutralizing protein, rBPI23, was shown to partially prevent endotoxin-induced activation of the fibrinolytic and coagulation systems in experimental endotoxemia in humans. In a placebo- controlled, blinded crossover study, eight volunteers were challenged twice with an intravenous bolus injection of endotoxin (40 EU/kg of body weight) and concurrently received either rBPI23 (1 mg/kg) or placebo (human serum albumin, 0.2 mg/kg). rBPI23 treatment significantly lowered the endotoxin-induced fibrinolytic response, ie, reduced the release of tissue-type plasminogen activator, urokinase- type plasminogen activator, plasminogen activator inhibitor antigen, and complex formation of plasmin alpha 2-antiplasmin (P = .0078 for each). Plasminogen activator inhibitor activity was also reduced, but not significantly according to the Hochberg method (P = .0304). The endotoxin-induced activation of the procoagulant state as reflected by increase in F1 + 2 fragments and TAT complexes was blunted by rBPI23 infusion (P = .0391 [not significant according to the Hochberg method] and .0078, respectively). These results indicate that rBPI23 is capable of reducing both the activation of the fibrinolytic and the coagulation systems after low-dose endotoxin infusion in humans.     

Interactions in the aetiology,presentation and management of synchronous and metachronous adenocarcinoma of the prostate and rectum

Adenocarcinoma of the prostate and rectum are common male pelvic cancers and may present synchronously or metachronously and, due to their anatomic proximity. The treatment of rectal or prostate cancer (in particular surgery and/or radiotherapy) may alter the presentation, incidence and management should a metachronous tumour develop. This review focuses on the interaction between prostatic and rectal cancer diagnosis and management. We have restricted the scope of this large topic to general considerations, management of rectal cancer after prostate cancer treatment and vice versa, management of synchronous disease and cancer follow-up issues.     

The development of contact hypersensitivity in mouse skin is suppressed by tumor promoters

The ability of tumor promoters to suppress the development of contact hypersensitivity (CHS) was assessed by the mouse ear swelling assay. Application of the complete or second stage tumor promoters phorbol-12-myristate-13-acetate (PMA, 2 micrograms), croton oil (1%), benzoyl peroxide (20 mg), mezerein (2 micrograms), or phorbol-12-retinoate-13-acetate (PRA, 2 micrograms) to the abdominal surface of CF-1 female mice for 1 week (three treatments) prior to the sensitization of the same location with 0.5% 1-chloro-2,4-dinitrobenzene (DNCB) resulted in a 50% suppression (p less than 0.05) of the CHS response to DNCB. The first stage tumor promoters 4-O-Me-PMA (80 micrograms), calcium ionophore A23187 (80 micrograms), hydrogen peroxide (15%) and the non-promoting analogs phorbol-12,13-diacetate (PDA, 20 micrograms), phorbol (80 micrograms) or acetone did not suppress the response. The suppression of the development of CHS caused by PMA was dependent on the promoter being applied at the site of induction and was inhibited by application of the phospholipase A2 inhibitor dibromoacetophenone (100 micrograms), the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 100 micrograms), or the antiinflammatory steroid fluocinolone acetonide (2 micrograms). Application of PMA or mezerein 24 h prior to challenge with DNCB, to the ears of mice previously sensitized with DNCB resulted in a significant enhancement of the ear swelling response by 60% and 110%, respectively, compared with controls. The results demonstrate that tumor promoters suppress the development of CHS, and suggest the possibility that second stage promotion may involve suppression of the development of a tumor specific immune response.