Transplantation Antigens and Malignant Lymphomas in Man: Follicular Lymphoma, Reticulum Cell Sarcoma and Lymphosarcoma

134 patients with malignant lymphoma (follicular lymphoma, 56 patients; lymphosarcoma, 50 patients; reticulum cell sarcoma, 28 patients) have been typed for eight well-defined antigens of the HL—A system, the major histocompatibility system in man. A significant association exists between HL—A12 and this disease group. This is most marked for the patients with follicular lymphoma. The significance of this finding is discussed.     

Palliative care in patients with cancer of the head and neck

Palliative care is the active total care of patients whose disease is not responsive to curative treatment. Patients with end-stage head and neck cancer have particular problems because of the impact of the tumour on the airway, the upper gastrointestinal tract and the major senses. Patients referred for palliative care were identified from the hospice database and the nature, incidence and management of their problems, and the role of the hospice in their care, was reviewed from in-patient and home care notes and patient-generated problem lists. Thirty-two male and six female patients with a median age of 64 years were identified. Locoregional recurrence was present in 79% of patients. Pain, weight loss, feeding difficulties, dysphagia, respiratory symptoms, xerostomia, oral thrush and communication difficulties were the major problems. The management of each, and of the terminal events encountered in the group, is discussed.     

PLATELET SENSITIVITY TO A PROSTACYCLIN ANALOGUE IN SYSTEMIC SCLEROSIS

Vascular prostacyclin (PGI₂) regulates platelet function andblood flow. In systemic sclerosis (SS) there is increased plateletaggregation (PA) but no information is available on the platelet/PGI₂relationship. We evaluated platelet sensitivity to a PGI₂ analogueZK36374 in 17 SS patients and 18 controls. The percentage (%)inhibition of PA was measured at two doses of ZK36374 with salinegiving the 100% baseline. In the SS group 2ng ZK36374 produceda percentage inhibition of 19 + 14 compared to a control valueof 60 + 21, and 3 ng a percentage inhibition of 47 + 21 in theSS group and 82 + 20 in the controls. In 11 SS patients treatedwith either prostaglandin E or nifedipine the sensitivity approachednormal. These data suggest that SS platelets are less sensitiveto the inhibitory effect of PGI₂ on PA. This may contributeto the vascular lesions of SS. Other cells are resistant tothe effects of PGI₂ and our findings support this picture ofcellular resistance KEY WORDS: Systemic sclerosis, Raynaud's syndrome, Prostacyclin Platelets     

DOSAGE-RELATED EFFECTS OF DANAZOL ON SEX HORMONE BINDING GLOBULIN AND FREE AND TOTAL ANDROGEN LEVELS

Danazol is known to cause marked suppression of sex hormone binding globulin (SHBG) levels in plasma and to increase the proportion of plasma testosterone unbound to protein but the effect on the concentration of total and free testosterone is unclear. Twenty-five patients with endometriosis were treated daily for 6 months with doses of danazol ranging from 50 to 600 mg. The fall in SHBG and rise in percent free testosterone was dose-related during the early part of treatment. Suppression of total testosterone and 5 alpha-dihydrotestosterone levels occurred and was probably due to increases in metabolic clearance rates. The observed fall in androstenedione levels was related to the incidence of menstrual abnormality, suggesting that this might be due to reduced ovarian activity. The concentration of free testosterone increased by a factor of two in the first week but subsequently returned to levels of between 25 and 50% above pretreatment levels. This pattern of changes may be due to the rise in metabolic clearance rates being dependent on induction of enzymes of androgen metabolism.     

FIBRINOLYSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS: EFFECT OF DESAMINO D-ARGININE VASOPRESSIN INFUSION

In systemic lupus erythematosus (SLE) the lupus anticoagulantis known to be associated with thrombosis. However, this anticoagulantonly occurs in a small percentage of patients. Histopathologicalstudies suggest a more generalized thrombotic tendency withplatelets and fibrin within the microvasculature. Fibrinogenis elevated in SLE and this may lead to the fibrin depositiondescribed. We wondered if decreased fibrinolysis contributedto this and we infused desamino D-arginine vasopressin (DDAVP)into ten patients with SLE and eight controls. DDAVP stimulatesendothelial production of plasminogen activator (PA) and factorVIII. Baseline results showed a significant decrease in PA activitywith a concomitant increase in fibrinogen in SLE. The t-PA andinhibitor levels were normal but factor VIII was increased.After infusion of DDAVP, results indicated that, despite baselineresults, SLE patients were able to respond to stimulation andthe increase in PA activity produced a decrease in plasma fibrinogenlevels. These findings may have therapeutic implications. KEY WORDS: Systemic lupus erythematosus, Fibrinolysis, Factor VIII     

Opioid responsiveness

Cancer pain generally responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment. A small proportion of patients, of the order of 20%, have pain that does not respond well to conventional analgesic management. Because opioid analgesics are the most important part of this pharmacological approach, a terminology has developed which centres around whether or not pain will respond to opioid analgesics. The terms opioid-responsive-pain and opioid-non-responsive pain, or opioid-resistant-pain, have been used to differentiate between patients whose pain falls into these two broad groups. This terminology is not satisfactory because it implies an all or none phenomenon, that is that pain either does or does not respond to opioid analgesics. Rarely is there such a clear distinction in practice. This is because the end point when titrating dose against pain with strong opioid analgesics is not simply pain relief or lack of relief: adverse effects may limit dose titration. It is preferable to describe patients with pain which is relatively less sensitive to opioids and/or patients where there is an inbalance between analgesia and unwanted effects as having “opioid-poorly-responsive pain”. A pragmatic definition of opioid-poorly-responsive pain is pain that is inadequately relieved by opioid analgesics given in a dose that causes intolerable side effects despite routine measures to control them. Included in this definition is so called paradoxical pain which is not a distinct entity. Neuropathic pain is the most common form of opioid-poorly-responsive pain. The underlying pathophysiology remains unclear but abnormal metabolism of morphine is not the cause of a poor response to this drug. Patients with opioid-poorly-responsive-pain should be considered for treatment with the same opioid by an alternative (spinal) route or with an alternative opioid agonist administered by the same route (whether oral or parenteral), in conjunction with adjuvant analgesics such as tricyclic antidepressants. The most commonly used alternative oral opioids are phenazocine and methadone; transdermal fentanyl is an additional option.