Idiopathic retroperitoneal fibrosis. A retrospective analysis of 60 cases

Sixty patients with idiopathic retroperitoneal fibrosis presenting between 1965 and 1984 are reviewed. Their mean age at presentation was 56 years and the male:female ratio was 3:1. The commonest presenting symptoms were flank and abdominal pain, weight loss, nausea and polyuria. Physical examination was usually normal, expect for the presence of hypertension. Anaemia and elevation of erythrocyte sedimentation rate were usually present. Proteinuria was found in less than a third of patients at presentation and significant bacteriuria was uncommon. The correct diagnosis was made or suspected in very few patients before referral. The cumulative actuarial survival rate was 86% at 1 year and 78% at 2 years. Seventeen patients died; they were significantly older and more uraemic at the time of referral than those who survived. A few patients did well with either corticosteroid therapy or ureterolysis alone. In the majority, both operation and steroid treatment were necessary. In bilateral obstruction with residual function in both kidneys, bilateral ureterolysis proved superior to unilateral operation (each followed by steroid therapy) in conserving renal function. Operation alone or steroid therapy alone should be considered in cases where steroids or surgery respectively present particular hazards. The less traumatic unilateral operation should be considered in poor risk patients and in those whose renal function is absent on one side. In many survivors, disease activity has persisted for many years. Life-long follow-up is recommended.     

Interactions of cholecystokinin and glucose in rat pancreatic islets

The effects of sulfated cholecystokinin (CCK-8S) and glucose on insulin secretion and polyphosphoinositide (PPI) metabolism were studied in isolated rat islets. Both agonists stimulate PPI hydrolysis, inositol phosphate accumulation, 3H efflux from [3H]inositol-prelabeled tissue, and 45Ca efflux from prelabeled cells. However, the effects of CCK-8S on PPI metabolism are considerably greater than those of glucose. Furthermore, the effects of CCK-8S on PPI and Ca2+ metabolism are observed whether islets are incubated in either 2.75 or 7 mM glucose, but CCK-8S only stimulates insulin secretion (a biphasic response) when the higher glucose concentration is present. Addition of 1 microM forskolin to islets incubated in media containing 2.75 mM glucose does not influence basal insulin secretion but sensitizes the islets to the action of CCK-8S. In the presence of forskolin, CCK-8S induces a very marked first phase but no second phase of insulin secretion. We postulate that CCK-8S acts in this tissue via receptor-linked PPI hydrolysis, leading to an inositol trisphosphate-induced Ca2+ efflux. These receptor-mediated effects of CCK-8S are not altered either by the ambient glucose concentration or the cAMP content of the islets, but these two factors determine the responsiveness of the islets (in terms of insulin secretion) to a given CCK-8S signal.     

Electrophysiologic effects of d-sotalol in humans

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.     

Phase II study of iproplatin in metastatic breast carcinoma

Thirty patients with progressive metastatic breast cancer and one prior chemotherapy regimen were treated with iproplatin at a starting dose of 300 mg/m2 iv every 3 weeks. After the first 11 patients, the starting dose was decreased to 270 mg/m2. There were one complete remission, three partial remissions, and two minor responses. Responses were observed in soft tissue and osseous and visceral areas. Grade 3 nausea and vomiting were observed in 38% of patients, and grade 3 diarrhea occurred in 31%. The dose-limiting toxicity was thrombocytopenia, which required dose de-escalation in 15 patients. No nephrotoxicity, neurotoxicity, or ototoxicity was observed. Iproplatin has modest antitumor activity in this group of previously treated patients with metastatic breast cancer.     

A survey, in Scotland, of measures to prevent infection following orthopaedic surgery

The current use of methods, in Scotland, to prevent infection following orthopaedic surgery was established by postal questionnaire. Thirty-five per cent of surgeons used antibiotic cement routinely for total hip replacement. Ultraclean air facilities were provided for only 19%. Ninety-one per cent of surgeons used prophylactic parenteral antibiotics during total hip replacement, 75% in the management of open fractures, but only 12% for metal implants. Most chose an appropriate antibiotic. Only one-third of surgeons used an antibiotic regimen of appropriate duration and timing for total hip replacement or when employing metal implants.     

Lymphocytes capable of mediating delayed-type hypersensitivity reactions accumulate within sponge matrix allografts

The rejection of sponge matrix allografts across H-2 barriers has generally been found to contain specifically sensitized cytotoxic T cells to donor alloantigen. There is one exception: sponge matrix allografts that differ only with respect to class II alloantigens do not contain specifically sensitized cytotoxic T cells. We therefore investigated the capacity of infiltrating cells removed from sponge matrix allografts to generate delayed hypersensitivity reactions after exposure to fresh alloantigen in a footpad assay. Cells infiltrating class I and II allografts were equally capable of eliciting delayed footpad reactions when injected with specific donor alloantigen into the footpads of naive responder strain mice. Allosensitized T-lymphocyte clones of helper or cytotoxic type were also capable of initiating delayed-type hypersensitivity (DTH) reactions in vivo. We conclude that rejecting allografts across class I or II alloantigenic barriers are infiltrated by cells capable of effecting DTH reactions, in addition to their capacity to exert specific helper or specific cytotoxic reactions. The results also support that both helper and cytotoxic T cells can participate in allospecific DTH reactions.