Reflex Cardiorespiratory Effects of Nociceptive Oesophageal Distension in the Decerebrate Rat

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.     

Concurrent review of the duration of antimicrobial prophylaxis in surgery.

The administration of prophylactic antibiotics in surgery is appropriate for many patients. Data have shown extending the duration of prophylaxis beyond 48 hours does not lower the rate of postoperative-infection. The purpose of this project was to concurrently assess the duration of prophylactic antibiotic use. A total of 95 patients were monitored over 3 weeks. Eighty patients (84.2%) received antimicrobial therapy. In 23 of these patients (28.75%) the duration of antibiotic administration was longer than 2 days without clinical or microbiological evidence of infection. In 5 other patients only postoperative antibiotics were prescribed. The cost difference between the actual duration of antibiotic administration and 2 days of the same regimen was +1,364.58. Extrapolating for one year, it can be estimated that antibiotic costs could be reduced about +23,600. Pharmacists can focus on the duration of antibiotic prophylaxis as a cost containment measure.     

The General Practice Research Club.

The General Practice Research Club was established in 1969, and now has 120 members. A meeting of the club is held twice a year, at which various papers, from research ideas through to completed, published studies are presented. A survey of 40 individuals who had presented papers at meetings during the period 1984-89 showed that almost half (18) had presented papers on clinical topics. As a result of the presentation, 29 individuals had modified their research, with 11 undertaking major alterations. The meeting was rated most highly by those offering ideas and plans for research. Most individuals responded positively to the meetings, commenting that they valued peer review, found the meetings encouraging, and useful for focusing ideas. Lack of criticism and feedback was commented upon. The club has an important role to play in encouraging research by service general practitioners.     

Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

CT evaluation of Crohn's disease: effect on patient management

CT scans from 80 consecutive patients with clinically symptomatic Crohn's disease were reviewed retrospectively to determine the effect of CT diagnosis on patient management. The initial clinical impression and any subsequent change in patient management because of the CT findings were noted. In 22 (28%) of the 80 patients, significant previously unsuspected findings led to a change in medical or surgical management. These included 12 patients with fistulae, four with abscess, two with avascular necrosis of the femoral head, two with sacral osteomyelitis, and single cases of pelvic inflammatory disease and femoral vein thrombosis.     

Computed tomography findings in gastrointestinal involvement by opportunistic organisms in acquired immune deficiency syndrome

The computed tomography findings in two cases of gastrointestinal superinfection by opportunistic organisms in acquired immune deficiency syndrome are presented. Findings included thickening of the mucosal folds and the bowel wall in the small intestine and colon associated with cytomegalovirus and cryptosporidiosis. These cases indicate that it is important to look carefully at the gastrointestinal tract when performing computed tomography in this group of patients. Unsuspected bowel pathology may be demonstrated, or disease may be confirmed in clinically suspected cases.     

Elevated levels of the NR2C subunit of the NMDA receptor in the locus coeruleus in depression.

Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NRI and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher (+ 61%, p = 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum (+ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.