Induction of esophageal tumors in zinc-deficient rats by single low doses of N-nitrosomethylbenzylamine (NMBA): analysis of cell proliferation, and mutations in H-ras and p53 genes

Dietary zinc deficiency in rats induces hyperplasia in the esophagus and increases N-nitrosomethylbenzylamine (NMBA)-induced esophageal tumor incidence. Previous work showed a direct relationship between epithelial cell proliferation and esophageal tumor incidence in rats given multiple doses of NMBA. We investigated the effects of single low doses of NMBA in zinc-deficient rats since a single dose of 5.0 mg/kg was reported to be non-carcinogenic in rats. Zinc-sufficient and deficient rats received a single i.g. dose of NMBA at 0.5 or 2.0 mg/kg. At week 14, tumor incidence was 50% with 0.8 +/- 1.0 tumors/rat, and 80% with 2.2 +/- 1.9 tumors/rat, in deficient groups, D(0.5) and D(2.0), that received the lower and higher dose, respectively. In addition, two small papillomas were found in one out of eight untreated zinc-deficient rats. None of the NMBA-treated or untreated zinc- sufficient rats had any tumors. Esophageal cell proliferation, as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry, showed that, irrespective of NMBA treatment, deficient esophagi had significant increases in the number of labeled cells, the total number of cells, and the labeling index, as compared with zinc-sufficient ones. Mutations in Ha-ras and p53 genes in esophageal tumors were detected by single strand conformation polymorphism (SSCP) analysis. DNA sequencing of variant conformers revealed a point mutation (GGA-->GAA, codon 12) in Ha-ras in 4/5 (80%) and 5/8 (63%) tumors, from D(0.5) and D(2.0) rats, respectively. Three out of eight tumors from D(2.0) rats exhibited SSCP mobility shifts within p53 exons 5 and 7: two tumors (2/8, 25%) had missense mutations and the third, a silent mutation. Of the two tumors with p53 mutations, one had a double mutation (transition at codon 164, TCA-->TTA; transversion at codon 241, AGT-->TGT), and the other tumor, a transition at codon 172 (AGA-->GGA), with amino acid changes in all cases. In parallel with PCNA expression, elevated p53 expression was associated with hyperplastic and dysplastic regions, as well as with tumors, in deficient esophagi. In short, these data indicate that dietary zinc deficiency, with its associated sustained increased cell proliferation in the esophagus, can drive an otherwise non-tumorigenic dose of NMBA into a highly tumorigenic one.      

Steroids for intubated croup masking airway haemangioma

Recently, the beneficial role of steroids for acute laryngotracheobronchitis has been more clearly defined for both intubated and unintubated patients. However, corticosteroids also improve the clinical signs of airway haemangiomata. Two patients are described who illustrate how this can be a source of diagnostic confusion.     

Colorectal hemangioma: radiologic findings

The authors correlated radiographs with the clinical and histologic data of 12 patients with colorectal hemangioma. All patients presented with rectal bleeding, which was chronic in seven. Phleboliths were also visible in seven cases, which correlated with chronic bleeding in five. On barium studies, three masses were soft and three produced rigid narrowing. The atypical features of rigid luminal narrowing, which might mimic a carcinoma, and hypovascularity correlated with chronic bleeding or visible phleboliths, which suggest the correct diagnosis of colorectal hemangioma.     

Roxatidine versus ranitidine in the treatment of duodenal ulcers: A randomized double-blind controlled multicentre study in Singapore

Roxatidine acetate, a new H₂ receptor antagonist, was compared with ranitidine in the treatment of duodenal ulcers in a double-blind multicentre study. Eighty-four patients with endoscopically proven duodenal ulcer were randomized to receive 150 mg roxatidine acetate or 300 mg ranitidine at bedtime. Repeat endoscopy was performed after 4 weeks (25–33 days) and if the ulcer had not healed, another endoscopy was performed after a further 4 weeks of treatment. Using per protocol analysis 73.6% of ulcers treated with roxatidine healed at 4 weeks compared to 72.2% of ulcers treated with ranitidine (P=NS). The healing rates at 8 weeks were 92% with roxatidine and 83.3% with ranitidine (P=NS). Using equivalence tests, the healing rate of roxatidine was found to be equivalent to that of ranitidine within a 20% region. Roxatidine users took significantly less antacids than ranitidine users (P < 0.05). There were no significant adverse effects due to roxatidine or ranitidine. Roxatidine is a safe effective drug in the treatment of duodenal ulcers with a healing rate comparable to that of ranitidine.     

Movement detection at the ankle following stroke is poor

This study assessed whether sense of movement is impaired at the ankle in persons post-stroke who are able to walk independently. Eleven chronic post-stroke subjects (> 4 months post stroke) who were ambulatory with or without walking aids and living within the community, and 10 healthy age-matched control subjects volunteered to participate. Proprioceptive acuity at the ankle, measured by sense of movement, was tested at three velocities, 0.1, 0.5, and 2.5 deg/sec, in random order. In addition, ankle range of motion and the distance that subjects walked in 6 minutes were assessed. Stroke subjects were significantly poorer (p < 0.001) at detecting movement at the affected ankle compared with either the unaffected ankle or with the control group at each of the velocities tested. Six out of 11 stroke subjects demonstrated significant impairment in movement detection compared to controls. The usual primary impairments following stroke are loss of strength and loss of co-ordination. However, reduced proprioceptive acuity at the affected ankle may also contribute to a person's ability to position and load the foot during walking. This could explain the moderate relationship found between proprioceptive acuity and walking endurance in persons following stroke (Spearman's rho = 0.63 to 0.77).     

Sensorimotor control is impaired in dancers with functional ankle instability

BACKGROUND: Factors potentially causing chronic instability after ankle inversion sprains have rarely been examined during the injuring movement. PURPOSE: To compare control of ankle movement during quiet stance and after inversion perturbation in chronically unstable ankles (n = 16) with healthy controls (n = 26). METHODS: Movement control was measured as magnitude of lateral ankle oscillation, using 3SPACE Fastrak during single leg stance (baseline oscillation) in two foot positions, flat and demi-pointe. In both positions, time to resume baseline oscillation after inversion perturbation (perturbation time) of 15 degrees for the flat foot and 7.5 degrees on demi-pointe was also determined. RESULTS: Baseline oscillation on demi-pointe was significantly smaller (P < 0.005) for the sprained group (2.5 +/- 0.5 mm) than for controls (4.0 +/- 2.3 mm). Perturbation time for the flat foot was significantly longer (P < 0.05) for the sprained group (2.2 +/- 0.4 seconds) than for controls (1.8 +/- 0.5 seconds). However, failure rate was higher (P < 0.05) among the sprained group than controls for perturbation with the foot flat and baseline oscillation on demi-pointe. CONCLUSIONS: Findings demonstrated altered sensorimotor control in chronically unstable ankles. Those sprainers who successfully completed the tasks minimized oscillation. The impairments in the sprained group may reflect deficits in either movement detection, peroneal muscle response, or both.     

Professional responsibility in relation to cervical spine manipulation

Manipulation of the cervical spine is one of the few potentially life-threatening procedures performed by physiotherapists. Is it worth the risk? A comparison of risks versus benefits indicates that at present, the risks of cervical manipulation outweigh the benefits: manipulation has yet to be shown to be more effective for neck pain and headache than other interventions such as mobilisation, whereas the risks, although infrequent, are serious. This analysis is of particular concern because the conditions for which manipulation is indicated are benign and usually self-limiting. Because physiotherapists have legal and ethical obligations to the community to avoid foreseeable harm and provide optimum care, it may be prudent to determine who in our profession should perform cervical manipulation. That is, the profession could restrict the practice of cervical spine manipulation. Although all registered physiotherapists in Australia are entitled to perform cervical manipulation, few choose to use this intervention. Therefore, it might be feasible to encourage those practitioners who wish to use cervical manipulation to undertake formal education programs. Such a requirement could be embodied in a code of practice that discourages those without formal training from performing cervical manipulation. By taking such measures, we could ensure that our profession exercises wisdom in its monitoring and use of cervical manipulation.