Safety of same-day-discharge radial percutaneous coronary intervention: a retrospective study.

BACKGROUND: The safety and feasibility of same-day discharge percutaneous coronary intervention (PCI) is still controversial. METHODS: Patients (n = 943) had same-day discharge radial PCI between April 1998 and March 2001 in our hospital. Patients were contacted and asked whether they had entry site complications or a repeat angiogram and/or PCI within 24 hours and 1 month after the procedure. RESULTS: At the time the study was conducted, 811 patients responded, 38 patients had died, and 94 were alive but refused to participate or it was impossible to contact them; 27 patients (2.8%) visited their doctor and/or the hospital within 24 hours after discharge because of entry site complications, and 38 patients (4.0%) visited within 1 month. However, none of the patients had major access site complications or needed to be admitted to the hospital. Within 24 hours from discharge 17 patients (2%) reported chest pain, and only 1 (0.1%) required a repeat angiogram, which did not show target vessel occlusion. During the first month, 94 patients (11.5%) reported chest pain, 11 (1.3%) underwent a repeat angiogram, out of which 4 had subacute vessel closure; 2 of the 132 patients that we could not contact had subacute stent thrombosis within 1 month and died. CONCLUSIONS: None of the patients having same-day discharge radial PCI had major access site complications. Six patients (0.6%) had subacute vessel closure, but none had this during the first 24 hours after discharge. Same-day discharge radial PCI in certain low-risk patients is a safe and feasible strategy.

Erythropoietin reduces anemia and transfusions: A randomized trial with or without erythropoietin during chemotherapy.

BACKGROUND: Anemia has been reported to develop during preoperative chemotherapy with paclitaxel and carboplatin. The use of recombinant human erythropoietin (EPO) has been shown to reduce anemia and subsequent packed red blood cell transfusions. The current study is a report of a Phase III, prospective, randomized trial with or without EPO that confirms the original observations of less anemia and fewer transfusions in those patients randomized to receive EPO concurrently with paclitaxel and carboplatin. METHODS: Thirty patients with advanced head and neck or lung carcinoma were treated with 2 courses of paclitaxel, 230 mg/m(2), and carboplatin, 7.5 mg/mL/minute, repeated every 21 days. The treatment group was comprised of 15 patients randomized to receive concurrent EPO, 150 U/kg, 3 times per week; in patients deemed nonresponsive the dose was increased to 300 U/kg and 450 U/kg in subsequent courses. The control group was comprised of 15 patients randomized not to receive EPO. RESULTS: Twenty-seven patients were evaluable. After 2 courses of chemotherapy the mean hemoglobin decrease was 1.2 g/dL in the EPO group versus 2.8 g/dL in the control group (P = 0.037). There was a highly significant decrease in hemoglobin over time in patients who did not receive EPO (P = 0.008). After 4 courses of chemotherapy, fewer patients were transfused in the EPO arm: 2 of 13 (15%) in the EPO treatment group versus 5 of 14 (36%) in the control group. CONCLUSIONS: There was significantly less anemia and transfusions were reduced by 50% in patients randomized to receive EPO during chemotherapy with paclitaxel and carboplatin.

Blastic mantle cell leukemia: a previously undescribed form.

The leukemic phase of mantle cell lymphoma (mantle cell leukemia) is defined as an absolute lymphocyte count of greater than 4,000/microliter and characterized by the presence of relatively small, slightly irregular lymphocytes in the peripheral blood. Although a variant of mantle cell lymphoma with blastic morphsology exists and has been previously well described, a blastic morphologic variant of mantle cell leukemia has not been described. We report such a case in a 74-year-old male who presented with splenic rupture and an elevated white blood cell (WBC) count. The diagnosis was based on flow cytometric immunophenotyping and the cytomorphology of the peripheral blood.

A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.

BACKGROUND: Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. METHODS: Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). RESULTS: The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. CONCLUSIONS: Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.

Effects of blockade of vasopressin V-1 receptors on post-burn myocardial depression.

It has been suggested that post-burn myocardial depression may be due to coronary constriction which results in myocardial ischaemia. It has been demonstrated that the levels of vasopressin, a potent natural constrictor of blood vessels, increase four- to six-fold immediately after thermal trauma. Therefore, this substance could be responsible for post-burn coronary constriction and myocardial depression. This was tested using the dog anaesthetized with sodium pentobarbital receiving a 15 per cent total body surface area full thickness flame burn as the experimental model. Cardiac output was measured by the thermal dilution technique. Arterial blood pressure was sensed by a Stathem P-23 transducer. Cardiac force of contraction was measured by a Walton-Brody strain gauge arch sewn on the left ventricle. The results of this study showed a significant decrease in cardiac output, increase in peripheral resistance and decrease in myocardial force of contraction immediately after thermal trauma in untreated animals. The decrease in cardiac output and increase in peripheral resistance remained for the duration of the experimental observations (3 h). The decrease in force of contraction returned to pre-burn levels 1 h post-burn. Pretreatment of the experimental animals with d(CH2)5 Tyr(Me)AVP (SK&F 100273), a vasopressin V-1 receptor blocking agent, prevented the initial decrease in cardiac output, increase in peripheral resistance and decrease in the force of contraction. A correlation plot of peripheral resistance vs. cardiac force of contraction showed a positive correlation between these two variables in the pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Trauma induced increases in plasma vasopressin and angiotensin II.

Previous investigators have shown that hypotension will cause an increase in plasma levels of both vasopressin and angiotensin II. Significant increases in peripheral resistance after thermal trauma suggested that a similar increase in plasma vasopressin and angiotensin II levels might occur under this condition. This possibility has been studied in the pentobarbital anesthetized dog. Peripheral resistance was calculated from measured cardiac output and mean arterial blood pressure. Vasopressin and angiotensin II levels were measured by radio-immunoassay. The results of this study showed that vasopressin plasma levels increase 4 to 6 fold 15 minutes after thermal trauma and remained elevated (3 to 4 fold) for at least 6 hours. Angiotensin II increased in a linear manner from 15 minutes to 6 hours post trauma. At 6 hours post trauma angiotensin II plasma levels were 4 times pretrauma levels. For the first 4 hours post trauma there was a positive correlation between the sum of vasopressin and angiotensin II plasma levels and the increase in peripheral resistance. These results suggest that the trauma induced increase in peripheral resistance is due to increases in plasma vasopressin and angiotensin II.

Benefits of high-dose dopamine in experimental neonatal septic shock.

The benefits of dopamine resuscitation in neonatal shock are in doubt. To evaluate dopamine's effectiveness on regional perfusion and survival, neonatal pigs were subjected to fecal Escherichia coli peritonitis-induced septic shock and were randomly divided into equal groups. Control animals (Group I) were not resuscitated with dopamine. Dopamine resuscitation, as a continuous infusion of 5 micrograms/kg/min (Group II), 50 micrograms/kg/min (Group III), or 200 micrograms/kg/min (Group IV), began when cardiac output dropped 20% below baseline. Radiolabeled microspheres were used to assess regional perfusion. Survival was defined as no hemodynamic compromise at 24 hr. Increased survival time correlated with sustained increases in cardiac output and blood pressure in Group III, which were not observed in the other groups. Significant changes in multiorgan regional perfusion were also observed in Group III and correlate with the improved survival. These data suggest that higher than usual doses of dopamine may be beneficial in neonates with peritonitis-induced septic shock.

Relationship between membrane ATPase and shape changes in the dog erythrocyte.

The effects of heating blood to 57 degrees C on intraerythrocytic calcium, membrane ATPase activity and cell shape have been studied in canine blood. Intraerythrocytic calcium was determined by use of arsenazo III, membrane ATPase activity was determined by inorganic phosphorous formation and erythrocyte shape was determined by scanning electron microscopy. The results of this study showed that this degree of thermal trauma would cause a 27% increase in intraerythrocytic calcium and a 38% decrease in ATPase activity. During these changes in calcium and ATPase activity the erythrocyte changed form from biconcave to spherical. Addition of catalase (3,200 U/ml) to the blood prior to heating prevented the changes observed in intraerythrocytic calcium, membrane ATPase activity and shape. The addition of the free-radical generating combination of hypoxanthine-xanthine oxidase to blood produced a 20% decrease in membrane ATPase activity and a change in erythrocyte shape, but did not alter intraerythrocytic calcium. These results suggest that free-radicals are responsible for the changes in membrane ATPase activity. The observation that shape change occurs when ATPase activity has been decreased, but calcium has not been increased, suggests that membrane ATPase activity levels are more important in producing changes in erythrocyte shape than are intraerythrocytic calcium levels.

The relationship between post-burn increases in peripheral resistance and vasopressin.

Using the dog anaesthetized with sodium pentobarbital receiving a 15 per cent total body surface full skin thickness flame burn as an experimental model, it was observed that administration of the vasopressin, V-1 receptor, blocking agent d(CH2)5Tyr(Me)AVP (SK&F100273) prior to burn could significantly reduce the increase in peripheral resistance which occurs in untreated burned animals. At 30 min post-burn peripheral resistance was 60.2 +/- 7.8 units in treated animals and 117.1 +/- 16.8 units in untreated animals. At 60 min post-burn these values were 71.3 +/- 7.2 units and 117.0 +/- 13.5 units, respectively. Changes in cardiac output were significantly less in treated than untreated experimental animals. The mean arterial blood pressures were not significantly different. Plasma levels of vasopressin were measured by radio-immunoassay prior to burn and at 30-min intervals for 6 h following burn. At the time of taking blood samples for vasopressin levels, mean arterial blood pressure and cardiac output were measured and peripheral resistance was calculated. The results of this study showed that immediately post-burn vasopressin plasma levels increased from 6.2 +/- 2.2 pg/ml to 27.3 +/- 9.5 pg/ml and peripheral resistance increased from 62.3 +/- 6.3 units to 128.0 +/- 20.3 units. During the remaining 6 h of the experimental study both vasopressin plasma levels and peripheral resistance remained elevated. These results show that following thermal injury there is a significant release of vasopressin and suggest that the increase in peripheral resistance observed could be due in part to the vasoconstrictor action of the released vasopressin.

Effects of thermal trauma on cardiac force of contraction.

Previous studies have reported that administration of potent peripheral vasodilating drugs will significantly increase thermal trauma-induced depression of cardiac output. This finding suggests that most of the depression in cardiac output after thermal trauma is due to an increase in peripheral resistance and a decrease in venous return rather than a direct depression of myocardial contractile force. Studies have been carried out using a strain gauge arch sewn on the left ventricle to measure myocardial force of contraction in the mongrel dog anaesthetized with sodium pentobarbital and receiving a 15 per cent total body surface area full skin thickness flame burn. The results of this study showed a significant decrease in cardiac output immediately after burn, which persisted for 7 h. Myocardial force of contraction, measured in grams, fell immediately after burn and returned to pre-burn values by 3 h post-burn. In one series of animals, verapamil, a calcium-channel-blocking substance, was administered. In these animals cardiac output returned to pre-burn levels following the administration of the drug, but myocardial force of contraction remained significantly lower than pre-burn value for the duration of the experiment. Correlation coefficients comparing cardiac output and myocardial force of contraction showed no significant relationship between values in either untreated or verapamil-treated animals.

Effects of thermal trauma on dog erythrocyte ATPase and shape.

Studies have been carried out on dog erythrocytes to determine the effects of heating to 57 degrees C on membrane ATPase and erythrocyte shape. The results of these studies showed that after heating the blood there was approximately a 30 per cent decrease in membrane ATPase and an alteration of erythrocyte shape from biconcave to spherical. Additional studies of the effects of addition of arachidonic acid to erythrocyte-membrane homogenates demonstrated that this substance produced a dose-related inhibition of ATPase. If the additions were made to membranes from blood which had previously been heated, the effects of arachidonic acid and heat were additive. Addition of the hydroxyl-radical scavenger catalase to the blood before heating prevented the observed decrease in ATPase and prevented the change in shape to spherical. These results confirm the previous findings of Bessis that heat will cause a change in the erythrocyte shape from biconcave to spherical and suggest that the mechanism responsible for this change is an alteration in membrane ATPase. The observation that a similar response can be produced by arachidonic acid suggests that metabolism of this substance may generate agents which are capable of inhibiting erythrocyte membrane ATPase. The observation that catalase will prevent the ATPase inhibition and the change in erythrocyte shape suggests that hydroxyl-free radicals play an important part in this thermal trauma-induced response.

The urine anion gap: the critical clue to resolve a diagnostic dilemma in a patient with ketoacidosis.

Usually, ketoacidosis presents few if any diagnostic or therapeutic problems; in this article, we report a case where ketoacidosis was clinically occult and biochemically obscure. The patient presented with acute pancreatitis associated with a modest antecedent alcohol intake. Metabolic acidosis with a normal anion gap (10 meq/L) was observed together with moderate hyperglycemia and a 2 + (but not 4 +) test for serum ketones. None of the usual causes of metabolic acidosis with a normal anion gap was identified nor was there an obvious explanation for a reduction in unmeasured anion gap (e.g., hypoalbuminemia, dysproteinemia, or the presence of abnormal halides). Despite the initial normal anion gap, ketoacidosis was suspected clinically and this was confirmed by the elevated serum B-hydroxybutyrate of 8 mmol/L. We deduced that the serum unmeasured anions, which should have been increased by at least 8 meq/L, were being underestimated because of the effect of hypertriglyceridemia on the serum chloride determination. When the serum chloride was reestimated by a method not influenced by hyperlipidemia, the value was 102 mmol/L not 112 mmol/L and, when reevaluated, the anion gap was indeed appropriately elevated. In addition, the urine anion gap (Na + K - Cl) was 103 meq/L in the absence of renal disease. This indicated that the expected large quantity of urinary ammonium must have been masked by an even greater quantity of unmeasured anion; in this case proven by direct measurement to be B-hydroxybutyrate. Finally, metabolism of the alcohol ingested, which yields hepatic NADH, could explain, in part, the modest hyperglycemia and the absence of a 4 + test for serum ketones.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of catalase, indomethacin and FPL 55712 on vascular permeability in the hamster cheek pouch following scald injury.

The effects of scald injury and scald injury with pretreatment on plasma and water content were studied in the superfused hamster cheek pouch. Catalase (30,000 Units/kg), indomethacin (2.5 mg/kg) and FPL 55712 (2 mg/kg) were administered prior to 10 second scald with 100 degrees C normal saline. Plasma content was measured with 125 I serum albumin and water content was calculated by loss on drying. Significant (P less than 0.05) decreases in plasma content compared to scald alone were observed following pretreatment with catalase (29%) indomethacin (31%) or FPL 55712 (52%). Water content in scalded pouches was significantly reduced by catalase (29%) and FPL 55712 (42%). Pretreatment when combined also resulted in significant reduction of plasma content but not water content. Results suggest that free-radicals, prostaglandins and leukotrienes are involved in vascular response by scald injury.

Effects of verapamil on thermal trauma depressed cardiac output in the anaesthetized dog.

Thermal trauma to the anaesthetized dog results in an immediate, significant decrease in cardiac output, an increase in peripheral resistance and no significant change in mean arterial blood pressure. The administration of verapamil 1.0 mg/kg by slow intravenous injection produced a rapid increase in cardiac output and a decrease in peripheral resistance. Mean arterial pressure fell and returned to or nearly to pre-injection values within 30 min. The duration of the increase in cardiac output after a single dose of verapamil was approximately 1.5-2.0 h. Administration of a second 0.5 mg/kg dose of verapamil, 1.5 h after the first dose, increased cardiac output and decreased peripheral resistance. After the second dose of verapamil, cardiac output was significantly greater and peripheral resistance was significantly less than in untreated animals for at least 2 h.

Effects of sodium nitroprusside on thermal trauma depressed cardiac output in the anaesthetized dog.

Thermal trauma to the anaesthetized dog results in an immediate significant decrease in cardiac output, an increase in peripheral resistance and no significant change in mean arterial blood pressure. The infusion of sodium nitroprusside, 5 or 8 micrograms/kg X min, produced a significant increase in cardiac output and a decrease in peripheral resistance. Mean arterial blood pressure fell during the infusion and returned to pre-injection values immediately upon cessation of infusion. Cardiac output and peripheral resistance also returned to pre-infusion values upon cessation of infusion. A comparison between the responses to infusion of sodium nitroprusside and the administration of verapamil showed that infusion of sodium nitroprusside produced a slower onset of increase in cardiac output and a lower maximum increase in cardiac output than observed after verapamil.

A modified technique for permeability studies in the superfused hamster cheek pouch.

We report here a modification of the superfused hamster cheek model for use in vascular permeability studies. Radio-iodine labeled serum albumin (I-125 RISA) is injected prior to the superfusion period. Plasma content is calculated on a microliter/100 mg wet weight basis and compared to the contralateral (non-superfused) cheek pouch. Water content is calculated on a percentage basis and compared in the same manner. Results demonstrate that superfusion causes an increase in permeability of protein and water. Plasma content is reduced by catalase, indomethacin or FPL 55712 pretreatment, suggesting that free-radicals, prostaglandins and leukotrienes are released during superfusion. Water content increase is refractory to pretreatment. The advantages of this system and its application are discussed.

Free-radical inhibition of ATPase in hamster cheek pouch homogenates.

The effects of free-radicals generated by either the oxidation of hypoxanthine by xanthine oxidase (HX/XO) or the lipoxidation of arachidonic acid (AA) on the ATPase of the hamster cheek pouch has been studied. Cheek pouches were removed from female golden syrian hamsters and homogenized. ATPase activity was measured by the production of Pi at 37 degrees. HX/XO and AA were added at a final concentration of 9.6 X 10(-5) M HX with 5 X 10(-2) units HX and 5 X 10(-5) M AA with and without 1 X 10(-4) M ouabain. HX/XO produced a 24.7% inhibition alone and 35.0% when combined with ouabain. Ouabain alone produced a 7.1% inhibition. AA produced a 23.6% inhibition alone and 24.3% inhibition when combined with ouabain. Ouabain alone produced a 5.4% inhibition in this series. When AA was added in doses ranging from 1 X 10(-5) to 2 X 10(-3) M, a plot of percent inhibition versus log dose followed a typical sigmoid type curve. The IC50 was 1.5 X 10(-4) M. These results suggest that free-radicals are capable of inhibiting the ATPase found in the hamster cheek pouch tissues. The possible modes of action of the free-radicals in producing this inhibition are discussed.