Diabetic foot ulcers: prevention, diagnosis and classification

Diabetic ulcers are the most common foot injuries leading to lower extremity amputation. Family physicians have a pivotal role in the prevention or early diagnosis of diabetic foot complications. Management of the diabetic foot requires a thorough knowledge of the major risk factors for amputation, frequent routine evaluation and meticulous preventive maintenance. The most common risk factors for ulcer formation include diabetic neuropathy, structural foot deformity and peripheral arterial occlusive disease. A careful physical examination, buttressed by monofilament testing for neuropathy and noninvasive testing for arterial insufficiency, can identify patients at risk for foot ulcers and appropriately classify patients who already have ulcers or other diabetic foot complications. Patient education regarding foot hygiene, nail care and proper footwear is crucial to reducing the risk of an injury that can lead to ulcer formation. Adherence to a systematic regimen of diagnosis and classification can improve communication between family physicians and diabetes subspecialists and facilitate appropriate treatment of complications. This team approach may ultimately lead to a reduction in lower extremity amputations related to diabetes.     

Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity

We have identified mutations in Raf-1 that increase binding to Ras. The mutations were identified making use of three mutant forms of Ras that have reduced Raf-1 binding (Winkler, D. G., Johnson, J. C., Cooper, J. A., and Vojtek, A. B. (1997) J. Biol. Chem. 272, 24402-24409). One mutation in Raf-1, N64L, suppresses the Ras mutant R41Q but not other Ras mutants, suggesting that this mutation structurally complements the Ras R41Q mutation. Missense substitutions of residues 143 and 144 in the Raf-1 cysteine-rich domain were isolated multiple times. These Raf-1 mutants, R143Q, R143W, and K144E, were general suppressors of three different Ras mutants and had increased interaction with non-mutant Ras. Each was slightly activated relative to wild-type Raf-1 in a transformation assay. In addition, two mutants, R143W and K144E, were active when tested for induction of germinal vesicle breakdown in Xenopus oocytes. Interestingly, all three cysteine-rich domain mutations reduced the ability of the Raf-1 N-terminal regulatory region to inhibit Xenopus oocyte germinal vesicle breakdown induced by the C-terminal catalytic region of Raf-1. We propose that a direct or indirect regulatory interaction between the N- and C-terminal regions of Raf-1 is reduced by the R143W, R143Q, and K144E mutations, thereby increasing access to the Ras-binding regions of Raf-1 and increasing Raf-1 activity.     

Electrocardiographic abnormalities in hypothyroidism before and after exercise

Eleven men and 50 women with severe hypothyroidism were studied. All patients had a serum PBI less than 3.0 mug/100 ml, 131I 24 hours uptake less than 13% and a a photomotogram contraction and half relaxation time of 380 msec or more. Before exercise the mean +/- SE heart rate was 68.39 +/- 3.26/min, the PR interval 17.08 +/- 0.37 csec, the QRS voltage (sum of the QRS amplitude in leads I, II and III) 16.44 +/- 0.89 mm (10mm = 1.0 mV) and the T wave amplitude 0.06 +/- 0.15 mm. A significant correlation (p less than 0.05) existed between the PBI values and the QRS voltage. Following exercise there was a significant acceleration of the heart rate (+ 23.39/min, p less than 0.001), shortening of the PR interval (-0.66 csec, p less than 0.02) and T wave elevation (+ 0.40 mm, p less than 0.001). ST segment changes were not observed in any case. Replacement treatment in 7 cases resulted in a significant change in the resting heart rate (+ 11.86/min. p less than 0.025), PR interval (-3.28 mm, p less than 0.025) and T wave height (+ 2.50 mm, p less than 0.01). These findings suggest that exercise may be used in the differentiation between hypothyroidism and coronary heart disease. The theoretical importance of these findings is also discussed. An increase in cardiac energy demands during exercise may be the cause for some of the ECG changes observed on exertion.     

Effects of cognitively induced anxiety on hand temperature

This study explored the relationship of cognitively induced anxiety and hand temperature reduction in a nonclinical sample. Forty college students were randomly assigned to either the Anxiety Group or the Pleasant Group. Following a baseline period, individuals in the Anxiety Group discussed with the experimenter topics which were anxiety-producing for them. Individuals in the Pleasant Group discussed topics of a pleasant nature. During these discussions, hand temperatures were recorded from the palmar surface of the third finger on the dominant hand. Data analysis indicated that hand temperature decreases were significant only in subjects discussing anxiety-producing topics.     

Respiratory effects of extradural analgesia after lower abdominal surgery

Blood-gas tensions, FRC and volume of trapped gas (VTG) in the lung were measured in patients on the day before lower abdominal gynaecological surgery, and twice on the day following surgery, before and after establishing lumbar extradural block (EDB) using 0.5% bupivacaine to provide analgesia after operation. FRC and VTG were measured with the closed-circuit helium-dilution technique. Mean VTG was 175 ml before operation and 275 ml after operation. PaO2 decreased significantly after operation, and the changes in FRC and VTG that occurred were related qualitatively. EDB did not significantly alter FRC, VTG or PaO2. Individual changes in FRC could not be related to changes in VTG or PaO2. Although EDB provided effective analgesia, the variables measured did not indicate that EDB conferred an immediate respiratory advantage.     

Informal use of decision theory to improve radiological patient management

Six radiologists reviewed 50 urograms to determine whether arteriography or needle aspiration should be recommended for evaluation of a space-occupying renal lesion. In addition to their usual decision methods, they were encouraged to think about the problem from a decision theory viewpoint. No computations were required. It was found that even informal, non-numerical application of decision theory resulted in improved outcomes; further improvement was noted with explicit use of numerical methods.     

Tricyclic antidepressants. Prolonged plasma levels after overdose

Twenty-four patients hospitalized for overdose of a tricyclic antidepressant were monitored clinically, and serial plasma-drug measurements were taken for up to 144 hours. Six of 24 patients had maximum antidepressant plasma levels greater than or equal to 1,000 ng/ml, and their plasma levels at 96 hours ranged from 170 to 1,280 ng/ml. Patients ingesting substantial tricyclic overdoses may remain medically unstable for days. When high tricyclic levels persist, accurate psychiatric assessment is often impossible.     

Granulocytic sarcoma (chloroma) initially seen as acute mastoiditis

Granulocytic sarcoma (chloroma) is a localized tumefaction of immature granulocytes that is typically seen in association with myelogenous leukemia. The primitive cell population seen in biopsy material may be misinterpreted as histiocytic lymphoma or other sarcoma unless additional studies are performed. We saw a 36-year-old woman with promyelocytic leukemia in remission who had the signs and symptoms of an acute coalescent mastoiditis. Histologic examination of the surgical specimen, however, demonstrated a granulocytic sarcoma. Our case exemplifies some of the difficulties that may be encountered in the diagnosis of granulocytic sarcoma and illustrates the point that symptoms of an inflammatory process in a patient with a diagnosis of leukemia must be regarded with a degree of suspicion.     

Preliminary characterization and pathogenicity studies of a virus isolated from ticks (Ornithodoros coriaceus) and from tick-exposed cattle

Several viral isolates from ticks (Ornithodoros coriaceus) and from the blood of cattle which aborted after exposure to these ticks were found to be identical by reciprocal cross serum-neutralization tests. Characterization studies indicate that the virus is a member of the Togaviridae family, although specific identification is still incomplete. Whether its natural host is the tick or bovine animals is also unknown. Pregnant cows inoculated with the agent by all conventional parenteral routes, including intrafetal, delivered healthy calves at term. It was concluded, therefore, that it was not a bovine pathogen and that the abortions which occurred after tick-exposure were due to a 2nd agent in O coriaceus ticks which also harbor the virus. While several ciruses believed to be tick-borne have been isolated from cattle in various parts of the world, it is believed that the present report describes the first isolation in the Western Hemisphere for a viral agent from Argasid ticks which has been demonstrated to replicate in cattle.