Os tibiale externum: etiopathogenesis, cases, clinical aspect and treatment

Based on a consideration of the pathogenesis of os tibiale externum and how it relates to flat foot, the authors discuss the various hypotheses as to how pain is determined. In conclusion, they indicate treatment, and use three cases as examples.     

Drug mixture which improves survival of ischemic rabbit epigastric skin flaps

The chief aim of this study was to maximize flap survival by counteracting the pathophysiological changes occurring during ischemia-reperfusion. Rabbit epigastric skin flaps given 21 hours of ischemia were infused intra-arterially with selected drugs at the start of reperfusion. Compared with control infused ischemic flaps, which had a 33% survival rate on day 7 post-ischemia, significant improvement was found with vasodilators nitrendipine (61%) and prostacyclin (65%) and the thrombolytic agent urokinase (65%); marginal improvement with the free radical scavenger desferrioxamine (53%); but no change with streptokinase (44%), heparin (21%), and ATP-MgCl₂ (35%). A drug mixture comprising all of these agents except streptokinase and urokinase produced 87% survival, suggesting an additive effect. Biochemical assays on skin homogenates and blood implicated oxygen free radicals, neutrophil infiltration, and thromboxane in flap failure. These results imply that multiple factors are responsible for ischemic flap failure and that a mixture of drugs needs to be infused to counteract all of the detrimental changes. © 1994 Wiley-Liss, Inc.     

Current clinico-therapeutic trends in essential varicocele

The authors report their experience with the diagnosis and surgical correction of varicoceles in 20 patients. They stress the usefulness of the Doppler Ultrasound for the diagnosis of subclinical varicocele.     

Phosphodiesterase isozyme inhibition, activation of the cAMP system, and positive inotropy mediated by milrinone in isolated guinea pig cardiac muscle

The purpose of the present study was to examine the interrelationships among phosphodiesterase (PDE) isozyme inhibition, cAMP formation, activation of cAMP-dependent protein kinase (cAPK), and positive inotropy in isolated guinea pig cardiac muscle mediated by the cardiotonic/vasodilator agent, milrinone. Milrinone was a potent and selective inhibitor of the "low Km" cAMP PDE isozyme (peak III) isolated by diethylaminoethyl ether cellulose chromatography, with IC50 values of 0.7 microM for peak III PDE and 100 microM for peak I PDE. In isolated papillary muscles frozen at peak inotropic responses, positive and significant correlations were evident between isometric force development as a function of cAMP content (r = 0.72, p less than 0.05) or cAPK activity ratio, an index of activation of cAPK (r = 0.79, p less than 0.001), for concentrations of milrinone from 0.1-1000 microM. Similar correlations were evident in muscles frozen at peak inotropic responses for the beta-adrenoreceptor agonist isoproterenol (r = 0.96, p less than 0.001; r = 0.98, p less than 0.001, respectively), but not for ouabain or Bay K-8644. The temporal sequence of these events was also quantitated for concentrations of milrinone (100 microM) and isoproterenol (3 nM) that produced approximately a 100% increase in isometric force. Whereas early time interval of force development (30 s, 1 min, isoproterenol; 30 s milrinone) were not accompanied by significant increases in either cAMP content or cAPK activity ratio, peak increases in force development for both isoproterenol (2 min) and milrinone (1 min) were related to peak increases in cAPK activity ratios. In summary, these results show that significant increases in cAMP content or cAPK activation are correlated with positive inotropy in isolated guinea pig papillary muscles with milrinone. These correlations occur at concentrations of milrinone that inhibit cardiac PDE isozymes and are similar to the known cAMP-dependent cardiostimulant isoproterenol. These data support the hypothesis that selective PDE isozyme inhibition is a mechanism by which milrinone effects positive inotropy.     

An exploratory study of frequent pain measurement in a cancer clinical trial

The ideal methodology for quality of life (QOL) measurement in cancer clinical trials matches the evaluation to the anticipated outcomes, thereby increasing the likelihood that clinically relevant changes are captured. The present study explored the importance of such methodological tailoring in a phase II trial of paclitaxel and recombinant human granulocyte-colony stimulating factor (rhG-CSF) for metastatic breast cancer. Prior to the trial, clinical observation suggested that frequent short-lived episodes of pain might occur during this treatment regimen. Twenty-one patients provided longitudinal data for at least three cycles of chemotherapy. To assess transient pain, aroutine QOL assessment at baseline and every third cycle was supplemented with pain measurements twice weekly. The interval assessment included a multidimensional QOL instrument (Functional Living Index-Cancer) and measures of psychological state (Rand Mental Health Inventory), symptom distress (Memorial Symptom Assessment Scale), and performance status (Karnofsky Performance Status Score). The frequent pain measurements were acquired using visual analogue and categorical scales for pain intensity (Memorial Pain Assessment Card). From baseline to the end of cycle three, global pain scores declined and the results on other QOL measures were variable. The data obtained using these measures did not reveal the existence of episodic pains. In contrast, the twice weekly pain measurements clearly demonstrated transient severe pains in approximately half the patients. These data highlight the importance of specific measurement of troubling symptoms or other relevant QOL concerns at clinically appropriate intervals during the routine QOL assessment of clinical trials. The additional burden involved in these assessments is warranted if the information derived is highly relevant, would not be adequately captured otherwise and could improve therapy.     

Binocular Interactions in the Lateral Suprasylvian Visual Area of Strabismic Cats Following Section of the Corpus Callosum

Visually responsive neurons have been recorded in the lateral suprasylvian area (LSA) of cats raised with either a convergent or a divergent strabismus. In contrast to areas 17 and 18, where many studies have documented a profound loss of binocularly activated neurons following early strabismus, in the LSA the majority of cells could still be binocularly driven. Acute or chronic section of the splenium of the corpus callosum reduced but did not abolish binocularity in the LSA. We propose that the widespread callosal connections, the large size of the receptive fields and the peculiar internal circuitry of the LSA all concur in permitting the maintenance of binocular coding in spite of early misalignment of the eyes.     

Treatment of experimentally induced caval thrombosis with oral low molecular weight heparin and delivery agent in a porcine model of deep venous thrombosis

OBJECTIVE: This experiment evaluated enterally administered low molecular weight heparin (LMWH) combined with sodium N-[10-(2-hydroxybenzoyl)amino] decanoate (SNAD) for the treatment of induced venous thrombosis. SUMMARY BACKGROUND DATA: SNAD is a delivery agent that potentiates the gastrointestinal absorption of LMWH. METHODS: Forty female pigs were equally assigned to four groups: control (saline); enteral LMWH, 2,000 IU/kg; enteral SNAD, 50 mg/kg; and enteral LMWH, 2,000 IU/kg and SNAD, 50 mg/kg. Under fluoroscopic guidance, the infrarenal vena cava was occluded with a balloon catheter. Two milliliters of ethanol was injected into the distal vena cava. The inflated balloon catheter remained in situ for 5 days, at which time animals angiographically exhibiting thrombus were randomly assigned to the four groups. Study medications were dosed at 12-hour intervals by means of a gastrostomy tube placed previously. After 7 days of treatment, thrombus was extracted. A separate group of 10 animals was used to measure plasma antifactor Xa levels for 6 hours after enteral dosing of LMWH/SNAD. RESULTS: The amount of residual thrombus after treatment with enteral LMWH/SNAD was significantly decreased. Antifactor Xa levels were significantly elevated in the LMWH/SNAD group versus baseline. CONCLUSION: The combination of enterally administered LMWH and SNAD given for 7 days appeared to decrease caval thrombosis in this model of deep vein thrombosis. Enteral LMWH/SNAD effected an increase in plasma levels of antifactor Xa.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.