Volume effects in the irradiated canine spinal cord: do they exist when the probability of injury is low?

PURPOSE: The purpose of this study was to investigate volume effects in the irradiated canine spinal cord. MATERIALS AND METHODS: Eighty-nine beagle dogs were given 44-84 Gy photons in 4 Gy fractions to 4 or 20 cm lengths of thoracic spinal cord. As controls, 36 dogs were given 60-84 Gy in 2 Gy fractions to a 20 cm length of spinal cord and six dogs were unirradiated. Dogs were evaluated for clinical signs, and after euthanasia, for occurrence of gross lesions, severe lesions of massive hemorrhage, white matter necrosis and/or parenchymal atrophy and mild lesions of focal fiber loss. White matter vacuoles, meningeal thickness and dorsal root ganglia lesions were quantified. Data were analyzed to test for an effect of volume on dose-response curves. RESULTS: Significant volume effects were found between 4 and 20 cm lengths of irradiated spinal cord for gross lesions, severe lesions and mild lesions (8.3-15.0 Gy difference at the ED50 level). The ED50 in 4 Gy fractions for severe lesions was 56.9 Gy (95% CI 53.1-60.6) for 20 cm and 68.8 Gy (95% CI 64.5-75.1) for 4 cm fields. Significant improvements in the fit of data to dose-response curves resulted when using models with either parallel or non-parallel curves, but in either case an appreciable difference existed between curves at low probabilities of injury. Volume effects were present for meningeal thickness and slopes of dose-response curves were different. Clinical signs correlated well with severe lesions for 20 cm (ED50 = 54.0 Gy), but not for 4 cm fields (ED50 = 77.6 Gy). CONCLUSIONS: Volume effects exist for the occurrence of pathologic lesions in irradiated canine spinal cord. Clinical compensation for pathologic lesions occur at small, but not large irradiated volumes. There is insufficient data to support a decreased slope of dose-response curves with decreased volume. Volume effects estimated at the 50% level of spinal cord injury could also hold at low probabilities of injury characteristic of the clinic.

Drinking before endoscopy: milk or water?

BACKGROUND: The traditional fluid fast prior to endoscopy is unnecessary. We have previously shown that drinking water prior to endoscopy does not affect either the quality of mucosal views or residual gastric fluid volumes when compared to patients undergoing endoscopy after a standard fast. The present study was designed to establish whether milk, which may delay gastric emptying, could also be drunk prior to endoscopy without adverse effect. METHODS: Forty-eight patients (mean age 48 years, range 20 to 79) undergoing routine upper gastrointestinal endoscopy after overnight fast were randomized to drink 200 ml of either still mineral water or full fat milk. Endoscopy was performed 90 minutes later, when all residual gastric fluid was aspirated via the endoscope. Volume and pH of gastric aspirate were measured and the quality of the mucosal view at endoscopy recorded as poor, adequate, or excellent. RESULTS: No difference was shown between water (n = 27) and milk (n = 21) drinkers in residual gastric volume (mean +/- SEM, water vs milk) (16.0 ml +/- 1.5 vs 18.9 ml +/- 2.9) or pH (2.23 +/- 0.14 vs 2.48 +/- 0.14). Of those patients with poor, adequate, or excellent views, 4 of 4, 11 of 12, and 6 of 32 patients, respectively, were milk drinkers (chi-squared test for trend = 21.7, df = 1, p < 0.001), indicating significantly worse mucosal views in the group drinking milk. CONCLUSION: Drinking water up to 90 minutes prior to endoscopy is safe, but milk should be discouraged because of suboptimal mucosal views.

Assessment of residual gastric volume and thirst in patients who drink before gastroscopy.

BACKGROUND: Before endoscopy patients undergo an uncomfortable fluid fast to reduce the risk of gastric acid aspiration and to ensure good endoscopic views are obtained. However, fluids rapidly leave the stomach and thus a long fluid fast before endoscopy may not be required. AIMS: The object of this study was to establish whether drinking before endoscopy is safe and relieves patients' symptoms of thirst. PATIENTS AND METHODS: 88 patients with American Society of Anaesthesiologists classification of physical status grades I and II were recruited in a controlled randomised single blind trial. The volume and pH of gastric aspirate obtained at gastroscopy was assessed in patients who drank 330 ml of water a minimum 90 minutes before their endoscopy and compared with values in patients who starved overnight. RESULTS: 44 patients who drank ('drinkers') 330 ml of water a mean 117 minutes before their morning gastroscopy had a similar volume and pH of gastric aspirate compared with 44 patients starved overnight ('starvers'); median volume 12.5 ml versus 10 ml, median pH 2.0 versus 2.0; 'drinkers' versus 'starvers' (NS). Before endoscopy patients were asked to score their thirst and hunger ratings as either none, mild, moderate or severe. Ratings for moderate and severe thirst were grouped together for analysis. The percentage of drinkers compared with starvers in each group with no thirst, mild thirst, and moderate severe thirst was 63%, 46%, and 37% respectively (chi 2 test for trend p < 0.05). Hunger ratings were similar in the two groups. CONCLUSIONS: It is safe for elective day cases to drink a significant volume of water two hours before endoscopy and this alleviates symptoms of thirst.

Deep venous thrombosis in the spastic upper limb.

Deep venous thrombosis (DVT) of the upper extremity (UE) is an uncommon diagnosis, whereas DVT of the lower extremity is a well-known cause of morbidity and mortality in the rehabilitation patient. Patients with UE DVT secondary to venous stasis, vessel wall abnormalities, hypercoagulability, venous instrumentation and cancer have been previously reported in the literature. To our knowledge no case of DVT in a spastic upper extremity has been noted. A case report of a patient with UE DVT in a spastic extremity secondary to traumatic brain injury is presented, with a discussion of the aetiology, diagnosis and management of this disorder.

T-cell receptor gene rearrangement in canine mycosis fungoides: further support for a canine model of cutaneous T-cell lymphoma.

Canine cutaneous T-cell lymphoma (CTCL) is a morphologic and immunophenotypic simulant of human mycosis fungoides (MF) characterized by an infiltrate of atypical, hyperconvoluted, epidermotropic T cells. To further support our hypothesis that canine MF is a useful model for the study of human CTCL, we have used Southern blotting to search for clonal T-cell proliferations in canine MF. Cellular DNA was extracted from normal dog buffy coat cells (n = 8), lesional canine MF skin (n = 8), canine MF buffy coat cells (n = 7), normal dog skin (n = 3), and normal human buffy coat cells (n = 5), digested with a panel of restriction enzymes and Southern blotted onto nylon membranes. All cases of canine MF were also immunophenotyped with anti-canine monoclonal antibodies to CD4, CD8, CD18, CD45RA, canine class II, T-cell activation antigens, and pan-B-cell antigens. Normal dogs gave reproducible digestion patterns in blood and skin, which differed from the human germline patterns when probed with a human T-cell receptor (TCR), beta chain constant region (C beta) cDNA. Common germline bands between the species included the 3.5-kb Eco RI, 3.4-kb Bam HI, 5.4-kb Sac I. These results confirmed that the TCR-beta gene is evolutionarily conserved between dog and man. Immunostaining revealed that 3/7 cases were CD4+ canine CTCL and 4/7 were CD8+ canine CTCL. Rearranged bands, deletion of germline bands, as well as minor alterations in electrophoretic mobility were observed in lesional DNA from seven of eight cases of canine MF, with at least two restriction digests in each case. Dog rearrangements were best detected with Bgl II, Eco RI, Eco RV, and Sac I, whereas deletions were detected with Bgl II, Sac I, Eco RV, and Bam HI. These studies demonstrate the presence of clonal TCR rearrangement in canine MF, further supporting the similarity of this tumor to human MF and its role as an animal model of CTCL.

Comparison of computed tomography and radiography for detecting changes induced by malignant nasal neoplasia in dogs.

The ability of computed tomography and radiography to detect changes associated with nasal neoplasia was compared in dogs. Eighteen areas or anatomic structures were evaluated in 21 dogs for changes indicative of neoplasia. Computed tomography was superior (P < or = 0.05) to radiography for detecting changes in 14 of 18 areas. Radiography was not superior for detecting changes in any structure or area. Computed tomography reveals vital information not always detected radiographically to assist in providing a prognosis and in planning treatment for nasal neoplasms in dogs.

Dermal dendrocytes and T-cells in canine mycosis fungoides. Support for an animal model of human cutaneous T-cell lymphoma.

BACKGROUND: An extensive upper dermal network of human Thy-1+/Factor XIIa+ dermal dendrocytes (DD) exists in human mycosis fungoides (MF). METHODS: Immunophenotyping and morphologic studies on serial frozen and paraffin sections from 15 cases of canine MF were performed to see if a similar network exists in this disease, as has been proposed as an animal model of human MF. Primary antibodies were anti-human Factor XIIIa, Factor XIIIs, anti-canine Thy-1, CD4, CD8, CD18, CD45RA, Class II, MAC387, KP-1, EBM-11, and several other pan-T, pan-B, and pan monocyte markers. RESULTS: Thy-1+/Factor XIIIa+DD were seen in all cases and confirmed on identical cells by double immunofluorescence. These were seen throughout the upper dermis, similar to DD in human MF. Canine DD expressed the macrophage marker 2A2+, and were Class II+, CD4+, CD8-, CD18+, EBM11-, Factor XIII-, MAC387-, and KP-1. Epidermal and dermal lymphocytes in canine MF were Thy-1-, CD4+, CD8-, CD18+, CD45RA-, EBM11-, MAC387-, Factor XIIIa-, Factor XIIIs- in some cases, whereas others had a predominance of CD8+ lymphocytes. CONCLUSIONS: Thus, canine MF is immunophenotypically similar to human MF. Additional support for this disease as a model of human MF is demonstrated by the rich network of Thy-1+/Factor XIIIa+ DD in the upper dermis of canine MF similar to human MF.

Pathology of radiation injury to the canine spinal cord.

The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED50 of 56.9 Gy (51.3-63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED50 of 49.5 Gy (44.8-53.6 Gy 95% CI) in 4 gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done.

Stimulation of vagal pulmonary C-fibers by a single breath of cigarette smoke in dogs.

Inhalation of cigarette smoke into the lower airway via a tracheostomy evokes immediate apnea, bradycardia, and systemic hypotension in dogs. These responses can still be evoked when conduction in myelinated vagal fibers is blocked preferentially by cooling but are abolished by vagotomy, suggesting that they are mediated by afferent vagal C-fibers. To examine this possibility, we recorded impulses in pulmonary C-fibers in anesthetized, open-chest dogs and delivered 120 ml cigarette smoke to the lungs in a single ventilatory cycle. Pulmonary C-fibers were stimulated within 1 or 2 s of the delivery of smoke generated by high-nicotine cigarettes, activity increasing from 0.3 +/- 0.1 to a peak of 12.6 +/- 1.3 (SE) impulses/s, (n = 60); the evoked discharge usually lasted 3-5 s. Smoke generated by low-nicotine cigarettes evoked a milder stimulation in 33% of pulmonary C-fibers but did not significantly affect the overall firing frequency (peak activity = 2.2 +/- 1.1 impulses/s, n = 36). Hexamethonium (0.7-1.2 mg/kg iv) prevented C-fiber stimulation by high-nicotine cigarette smoke (n = 12) but not stimulation by right atrial injection of capsaicin. We conclude that pulmonary C-fibers are stimulated by a single breath of cigarette smoke and that nicotine is the constituent responsible.

Respiratory rhythmicity after extensive lesions of the dorsal and ventral respiratory groups in the decerebrate cat.

It was previously demonstrated that extensive destruction of the regions of the dorsal (DRG) and rostral portions of the ventral respiratory groups (VRG) in the medulla does not disrupt respiratory rhythmicity in the anesthetized cat. The present experiments examined if either higher CNS structures or the caudal expiratory VRG might have been responsible for preserving rhythm in those studies. Results indicate that the DRG and VRG are not required for respiratory rhythmicity in the midcollicularly decerebrated cat.

Role of bronchopulmonary C-fiber afferents in the apneic response to cigarette smoke.

The role of vagal bronchopulmonary C-fiber afferents in eliciting the immediate changes in breathing pattern after acute inhalation of cigarette smoke was assessed with a selective blockade of myelinated vagal afferents (innervating both stretch and irritant receptors) utilizing the method of differential cooling. In 15 of 17 chloralose-anesthetized dogs tested, spontaneous inhalation of cigarette smoke (19.7% avg conc, 500-700 ml vol) reproducibly caused the following immediate responses: apnea, bradycardia, and hypotension. These responses occurred within 1 to 2 breaths of smoke inhalation and were followed by a delayed hyperpnea. The apneic duration reached 326 +/- 33% (SE) (n = 15) of the mean base-line expiratory duration. Differential cold block of both vagi (coolant temperature 8.4 +/- 0.3 degrees C) abolished the reflex apnea induced by a positive-pressure (7-10 cmH2O) lung inflation but did not affect the apneic response to smoke inhalation (345 +/- 35%). The smoke-induced apnea was completely abolished by lowering the coolant temperature to -1.3 +/- 0.2 degrees C (n = 10) or by bilateral vagotomy (n = 5) and returned to the control level after both vagi were rewarmed. Based on these results, we suggest that the immediate apneic response to inhaled cigarette smoke is elicited by a stimulation of vagal C-fiber afferents in the lungs and airways.

"It's me bowels".

Abnormal gastrointestinal symptoms are an obsession with some patients and come to dominate their lives. The normality of the investigations frequently contrasts sharply with the misery they proclaim, and suggests they may be suffering from the irritable bowel syndrome.

Erythema nodosum progressing to pyoderma gangrenosum as a complication of Crohn's disease.

Erythema nodosum occurs more frequently than pyoderma gangrenosum in Crohn's disease. We report the occurrence of both lesions in a woman with Crohn's disease and the transformation of one to the other. Pyoderma gangrenosum has been described at the site of previous trauma in Crohn's disease and at the site of other skin conditions in other circumstances, but, to the best of our knowledge, actual progression from erythema nodosum to pyoderma gangrenosum has been reported on only one previous occasion in Crohn's disease.

Coexisting retroperitoneal and mediastinal fibrosis.

A rare case of coexisting retroperitoneal and mediastinal fibrosis is reported. Increasing awareness of this association may lead to earlier recognition of significant symptoms and more effective therapy.