Repair of coarctation of the aorta in adults: the fate of systolic hypertension

BACKGROUND: The benefit of coarctation repair in adults has been questioned by suggesting that hypertension may not be relieved by the operation and that surgical intervention may have no impact on the natural history of the disease. METHODS: To delineate the impact of surgical intervention on systolic hypertension, we conducted a retrospective review of 26 adults with a mean age of 32 +/- 10 years who underwent coarctation repair between 1987 and 1993. All patients were hypertensive (mean systolic blood pressure, 174 +/- 21 mm Hg; range, 140 to 220 mm Hg), and 18 patients (69%) were on a regimen of at least one hypertensive medication at the time of surgical admission. All patients underwent catheterization, and the mean peak systolic gradient across the coarctation was 61 +/- 25 mm Hg (range, 25 to 120 mm Hg). Operation included resection and end-to-end anastomosis (3 patients), resection with an interposition tube graft (6 patients), a bypass graft (11 patients), and patch angioplasty (6 patients). There was no hospital mortality or late morbidity. RESULTS: Intermediate follow-up was available at a mean of 2.3 +/- 2 years (range, 1 to 7 years). At last follow-up, the peak systolic gradient between the upper and lower body was trivial (< or = 10 mm Hg) in 23 patients (88%) and mild (11 to 20 mm Hg) in 3 (12%). All patients had significant improvement in systolic blood pressure (p < 0.001) compared to preoperative values, and the majority (23, 88%) were normotensive. More than half of the patients (14, 54%) were still on a regimen of antihypertensive medication at last follow-up, with a trend (p = 0.06) toward older patients requiring medication. CONCLUSIONS: Surgical repair of coarctation in adults is an effective, low-risk procedure, which results in a significant improvement in systolic hypertension and a decreased requirement of antihypertensive medications.     

Synergistic augmentative effect of interleukin-10 and CD27/CD70 interactions on B-cell immunoglobulin synthesis

BACKGROUND: Patients who complain of constipation can be divided into those who have lost the natural call to stool, but develop abdominal discomfort after several days without a bowel movement (no urge); and those who experience a constant sensation of incomplete evacuation (urge). AIMS: To determine whether the two groups differ in symptoms, colonic transit, and perceptual responses to controlled rectal distension. METHODS: Forty four patients with constipation were evaluated with a bowel symptom questionnaire, colonic transit (radiopaque markers), and rectal balloon distension. Stool (S) and discomfort (D) thresholds to slow ramp (40 ml/min) and rapid phasic distension (870 ml/min) were determined with an electronic distension device. Fifteen healthy controls were also studied. RESULTS: All patients had Rome positive irritable bowel syndrome (IBS); 17 were no urge and 27 urge. Mean D threshold to phasic rectal distensions was 28 (3) mm Hg in no urge, 27 (3) mm Hg in urge (NS), but higher in the control group (46 (2) mm Hg; p < 0.01). Sixty seven per cent of no urge and 69% of urge were hypersensitive for D. Slow ramp distension thresholds were higher in no urge (S: 26 (3); D: 45 (4) mm Hg) compared with urge (S: 16 (2); D: 31 (3) mm Hg; p < 0.01), or with controls (S: 15 (1); D: 30 (3); p < 0.01). CONCLUSIONS: Hyposensitivity to slow rectal distension is found in patients with IBS who complain of constipation and have lost the call to stool even though their sensitivity to phasic distension is increased.     

Cytochrome P-450 inhibition blocks bone resorption in vitro and in vivo

BACKGROUND AND METHODS: To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). RESULTS: In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. CONCLUSION: The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.     

Splanchnic ischemia and bacterial translocation in the abdominal compartment syndrome

BACKGROUND AND METHODS: Major trauma or abdominal injury may lead to the development of increased intra-abdominal pressure (IAP) and the onset of the abdominal compartment syndrome. Although the effect of raised IAP on systemic and splanchnic hemodynamics have been described, the consequences of the resultant gut hypoperfusion in this setting are unknown. Bacterial translocation (BT) occurs after a period of splanchnic ischemia and may contribute to later organ failure. A rodent model was used to examine the effect of raised IAP on ileal mucosal blood flow (MBF) and BT. IAP was increased to 25 mm Hg for 60 minutes and mean arterial blood pressure was maintained with fluid. Animals were killed 24 hours later and examined for BT. RESULTS: Increased IAP resulted in a decrease of MBF to 63% of baseline despite maintaining normal mean arterial blood pressure. BT occurred principally to the mesenteric lymph nodes after 60 minutes of IAP at 25 mm Hg. CONCLUSIONS: Increased IAP leads to decreased MBF and to BT, which may contribute to later septic complications and organ failure.     

Telomerase activity and microsatellite instability in colorectal cancer and adenoma

BACKGROUND AND PURPOSE: We investigated the role of actin polymerization in regulating arterial diameter in response to increasing pressure and modulating forced dilatation of cerebral arteries at pressures above the upper limit of autoregulation. METHODS: Posterior cerebral arteries (n = 12) were isolated and pressurized in a special arteriograph that allowed control of intravascular pressure and measurement of lumen diameter. Intact arteries in the absence (control) or presence of 3.0 mumol/L cytochalasin B (CB), an inhibitor of actin polymerization, were subjected to stepwise increases in pressure from 75 to 200 mm Hg. Lumen diameter was continuously recorded, as was the pressure at which forced dilatation (loss of tone) occurred. After a period of time at 200 mm Hg, pressure was returned to 75 mm Hg and the extent of tone recovery was evaluated. RESULTS: Arteries with and without CB developed a similar amount of tone during equilibration at 75 mm Hg: percent tone = 27 +/- 3% for control versus 29 +/- 4% for CB arteries (P > 0.05). However, arteries in the presence of CB could not withstand pressure as well and underwent FD at significantly lower pressures: 168 +/- 5 mm Hg for control versus 142 +/- 5 mm Hg for CB arteries (P < 0.01). The amount of tone that arteries regained after FD when pressure was returned to 75 mm Hg was also less in CB arteries: percent tone = 34 +/- 3% for control versus 11 +/- 2% for CB arteries (P < 0.01). CONCLUSIONS: Cytoskeletal integrity appears important for maintaining cerebral arterial diameter during changing intravascular pressure. In addition, the process of actin polymerization may be a significant contributor to development of myogenic tone after forced dilatation.     

Transdiaphragmatic pressure gradients and the lower esophageal sphincter after tight abdominal wall plication in the rat

BACKGROUND: Gastroesophageal reflux (GER) is increasingly recognized as a complication of surgical closure of gastroschisis and omphalocele. AIM: This study tests the hypothesis that forceful abdominal wall closure reinforces the transdiaphragmatic pressure gradients that constitute the main GER-driving force and challenges the antireflux barrier. MATERIALS AND METHODS: Abdominal and esophageal pressures as well as lower esophageal sphincter pressures (LESP) and length (LESL) were measured in 17 adult rats before tight abdominal wall plication, after it, and 1 week later. RESULTS: This maneuver increased the transdiaphragmatic expiratory gradient from 0.67 +/- 1.31 to 6.97 +/- 2.68 mm Hg (P < .01) and the inspiratory gradient from 4.36 +/- 1.13 to 10.79 +/- 2.31 mm Hg (P < .01) by markedly increasing both the expiratory (from 1.47 +/- 0.74 to 9.44 +/- 1.85 mm Hg; P < .01) and inspiratory (from 0.98 +/- 0.69 to 6.83 +/- 1.55 mm Hg; P < .01) intraabdominal pressures. These changes were transient, and all pressures became normal after 1 week. The antireflux barrier functioned properly under these new conditions because both LESP and the diaphragmatic pinch-cock pressure (DPP) increased, from 20.3 +/- 3.63 to 26.5 +/- 4.31 mm Hg (P < .01) and from 16.4 +/- 7.25 to 22.5 +/- 4.36 mm Hg (P < .01), respectively, while LESL remained unchanged. CONCLUSION: Tight abdominal wall plication in the rat generates high intraabdominal pressures and thus reinforces the transdiaphragmatic pressure gradients, but these conditions elicit a healthy barrier response with sphincteric reinforcement. In addition, these changes are transient and fade out some time after operation. These facts should be taken into account for understanding the pathogenesis of GER after repair of abdominal wall defects in human babies.     

Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group

BACKGROUND: Despite treatment, there is often a higher incidence of cardiovascular complications in patients with hypertension than in normotensive individuals. Inadequate reduction of their blood pressure is a likely cause, but the optimum target blood pressure is not known. The impact of acetylsalicylic acid (aspirin) has never been investigated in patients with hypertension. We aimed to assess the optimum target diastolic blood pressure and the potential benefit of a low dose of acetylsalicylic acid in the treatment of hypertension. METHODS: 18790 patients, from 26 countries, aged 50-80 years (mean 61.5 years) with hypertension and diastolic blood pressure between 100 mm Hg and 115 mm Hg (mean 105 mm Hg) were randomly assigned a target diastolic blood pressure. 6264 patients were allocated to the target pressure < or =90 mm Hg, 6264 to < or =85 mm Hg, and 6262 to < or =80 mm Hg. Felodipine was given as baseline therapy with the addition of other agents, according to a five-step regimen. In addition, 9399 patients were randomly assigned 75 mg/day acetylsalicylic acid (Bamycor, Astra) and 9391 patients were assigned placebo. FINDINGS: Diastolic blood pressure was reduced by 20.3 mm Hg, 22.3 mm Hg, and 24.3 mm Hg, in the < or =90 mm Hg, < or =85 mm Hg, and < or =80 mm Hg target groups, respectively. The lowest incidence of major cardiovascular events occurred at a mean achieved diastolic blood pressure of 82.6 mm Hg; the lowest risk of cardiovascular mortality occurred at 86.5 mm Hg. Further reduction below these blood pressures was safe. In patients with diabetes mellitus there was a 51% reduction in major cardiovascular events in target group < or =80 mm Hg compared with target group < or =90 mm Hg (p for trend=0.005). Acetylsalicylic acid reduced major cardiovascular events by 15% (p=0.03) and all myocardial infarction by 36% (p=0.002), with no effect on stroke. There were seven fatal bleeds in the acetylsalicylic acid group and eight in the placebo group, and 129 versus 70 non-fatal major bleeds in the two groups, respectively (p<0.001). INTERPRETATION: Intensive lowering of blood pressure in patients with hypertension was associated with a low rate of cardiovascular events. The HOT Study shows the benefits of lowering the diastolic blood pressure down to 82.6 mm Hg. Acetylsalicylic acid significantly reduced major cardiovascular events with the greatest benefit seen in all myocardial infarction. There was no effect on the incidence of stroke or fatal bleeds, but non-fatal major bleeds were twice as common.     

Intravascular ultrasound for monitoring percutaneous fenestration of a membrane from an aortic dissection

HISTORY AND CLINICAL FINDINGS: A 51-year-old man, having experienced sudden retrosternal pain was admitted to another hospital with suspected myocardial infarction. He also had dysaesthesia and later paresis of the left leg. There was no sign of acute infarction in the ECG. However, computed tomography revealed aortic dissection, type III (DeBakey). The left pedal pulses were diminished. The patient was transferred to our hospital for further diagnosis and treatment. At a blood pressure of 110/60 mm Hg the occlusion pressure of the leg artery was 55 mm Hg on the left and 95 mm Hg on the right. INVESTIGATIONS: Transoesophageal echocardiography detected no abnormality of the aortic valve and ascending aorta. But distal to the origin of the left subclavian artery it demonstrated a free floating membrane of an aortic dissection and computed tomography showed its extension to the aortic bifurcation. TREATMENT AND COURSE: At first, because of the incomplete ischaemia syndrome affecting the left leg, a percutaneous fenestration of the dissection membrane was performed. After conventional angiography intravascular ultrasound imaging was also undertaken; it revealed that the membrane was almost completely occluding the left iliac artery. Under ultrasound monitoring a puncture needle and two balloon catheters were introduced across the membrane and thus a window created in it. The clinical findings quickly disappeared and the patient was discharged without further operation. CONCLUSION: Monitoring with intravascular ultrasound imaging makes it possible to perform safely a percutaneous fenestration of the membrane of an aortic dissection and to obtain immediate evidence of its success.     

The curative therapy of primary hyperparathyroidism by percutaneous ethanol injections

HISTORY AND CLINICAL FINDINGS: An 86-year-old woman was admitted because of acute nonspecific upper abdominal symptoms and vomiting. She was occasionally disoriented, generally slower in movement and reaction, apathetic and mainly bed-ridden. She was a known insulin-dependent diabetic who had sustained a posterior wall myocardial infarction and cerebrovascular accident and had undergone a cholecystectomy. On physical examination her upper abdomen was painful to pressure, blood pressure was 180/95 mm Hg, but there were no other findings. INVESTIGATIONS: Sonography demonstrated bile-duct dilatation, confirmed at endoscopic retrograde cholangiopancreatography, and a prepapillary choledochal concrement of about 10 mm. Sonography also revealed an echo-poor tumour of the right caudal parathyroid. The calcium concentration was raised to 2.94-3.16 mmol/l and the parathormone level was also increased (99.5 pmol/l, normal 1.2-5.7 pmol/l), as were amylase (375.6 U/l) and lipase (1038-5394 U/l). TREATMENT AND COURSE: After papillotomy and extraction of the choledochal concrement the acute biliary pancreatitis quickly improved. Operation on the parathyroid tumour was not undertaken because of the patient's various illnesses. Instead, 95% alcohol was instilled, 3.5 and 4.5 ml respectively, into the tumour, under sonographic control in two sessions, 3 days apart. Her clinical condition clearly improved and serum calcium became normal and the parathormone level fell significantly. CONCLUSION: Percutaneous ethanol injection of a parathyroid tumour can be a curative and sparing alternative to operation in patients with hyperparathyroidism seemed too ill for surgery.     

Genetic predisposition to hypertension facilitates blood pressure elevation in hemodialysis patients treated with erythropoietin

PURPOSE: This study investigated the hypothesis that a genetic predisposition to hypertension is involved in the etiology of the elevation in blood pressure induced by human recombinant erythropoietin (rHuEPO). PATIENTS AND METHODS: Blood pressure changes after 10 weeks of treatment with rHuEPO were compared between 26 patients with a positive family history of hypertension and 27 with a negative family history. RESULTS: Mean blood pressure was significantly increased in patients with a positive family history of hypertension (+8.8 mm Hg, p < 0.001). In contrast, the change was not significant in those whose family history was negative (+1.8 mm Hg, not significant). The mean blood pressure of 14 of 26 patients with a positive family history of hypertension increased by more than 10%, whereas such an increase occurred in only 2 of 27 patients with a negative family history (p < 0.001). The two groups were similar in terms of the total dose of rHuEPO given, the degree to which their anemia improved, and their basal blood pressures. CONCLUSION: It appears that hemodialysis patients with a positive family history of hypertension are susceptible to developing hypertension during treatment with rHuEPO.     

Unidirectional valve patch for repair of cardiac septal defects with pulmonary hypertension

BACKGROUND: Congenital septal defects with a large left-to-right shunt often cause pulmonary hypertension, which complicates surgical repair of the defects. METHODS: Twenty-four patients with congenital cardiac septal defects and severe pulmonary hypertension had operation to close the septal defect using a unidirectional valve patch during a 3-year period. The ratio of systolic pulmonary artery pressure to systolic arterial blood pressure was near to or more than 1.0 in all patients. RESULTS: Two patients died in the hospital after operation, and there have been no deaths during intermediate term follow-up. Mean pulmonary artery pressure decreased from 80 +/- 12 mm Hg to 56 +/- 18 mm Hg. The ratio of pulmonary artery pressure to systemic arterial pressure dropped from 1.1 +/- 0.1 mm Hg to 0.7 +/- 0.1 mm Hg. The unidirectional valve patch functioned allowing right to left shunting in 4 patients with a systolic pulmonary artery pressure more than systolic arterial blood pressure immediately after closure of a septal defect. The patch sealed or was effectively closed by the third postoperative day. There was impressive improvement in symptoms and exercise tolerance after operation during the 3-month to 3-year (mean, 1.1 year) follow-up period. CONCLUSIONS: The unidirectional valve patch is useful for management of patients having operation to close cardiac septal defects in the presence of severe pulmonary hypertension.     

Effect of local administration of mitomycin C on intraocular pressure

BACKGROUND: Animal studies suggest that the decrease of intraocular pressure after application of mitomycin C is particularly mediated by toxic effects on the substance of ciliary body. Moreover it has been shown that the concentration of mitomycin C after topical application in the aqueous humour is as high when performing fistulating surgery. In this prospective study we wanted to investigate whether the topical application of mitomycin C would result in a significant decrease of intraocular pressure. PATIENTS AND METHODS: Forty-one eyes of 41 patients underwent pterygium surgery using a bare sclera technique. Afterwards phototherapeutic keratectomy with the excimer laser (193 nm) was performed in the area of the excision. In hospital mitomycin C eye drops (0.02%) were given twice daily for four days. The intraocular pressure of treated and untreated eyes was measured with applanation tonometry at least three times per day preoperatively, postoperatively at the fourteenth day and after 6 month. RESULTS: Mean intraocular pressure of the treated eyes was preoperatively 15.73 +/- 2.35 mm Hg, 14 days postoperatively 15.92 +/- 2.79 mm Hg and at the last examination 15.86 +/- 2.39 mm Hg. For untreated eyes the mean intraocular pressure was preoperatively 15.70 +/- 2.04 mm Hg, after 14 days 15.76 +/- 2.96 mm Hg and at the last examination 15.89 +/- 2.67 mm Hg. Consequently there was no statistically significant change of intraocular pressure in the eyes treated with mitomycin C. Furthermore there were no significant differences of intraocular pressure between treated and untreated eyes at any time of postoperative check-up. CONCLUSION: The short-term local application of mitomycin C did not result in a detectable change of intraocular pressure and is therefore probably an alternative to intraoperative application during filtration surgery.     

Blood grouping problems

From 1965 to 1974, 53 children with coarctation of the aorta (COA) and an associated ventricular septal defect (VSD) underwent cardiac catheterization. Thirty-one patients presented with congestive heart failure. Twenty-five of 27 patients (92%) who underwent cardiac catheterization under age 3 months had either systemic hypertension, a systolic gradient across the coarctation greater than 20 mm Hg or both. Pulmonary hypertension was present in all 25 patients. COA repair was performed in 39 patients and there were seven deaths. Of the 32 survivors, 23 have no residual gradient; six are normotensive but have a mild residual gradient; three are hypertensive or have a gradient greater than 20 mm Hg. Repair of the VSD or pulmonary artery banding has been performed in 11 of 44 patients who survived infancy. Spontaneous closure of the VSD has occurred in three cases and 25 patients have a small VSD that does not warrant surgical repair. Surgical repair of COA during infancy may be unavoidable but conservative medical management of the associated VSD is often successful.     

Effects of intra-abdominal pressure on pharmacokinetics and tissue distribution of doxorubicin after intraperitoneal administration

Increased hydrostatic pressure in solid tumor nodules decreases the penetration of chemotherapy into cancerous tissue. This is true for both i.v. and i.p. chemotherapy. The purpose of this study was to determine the influence of increasing intra-abdominal pressures on the pharmacokinetics and tissue distribution of doxorubicin administered i.p. Four groups of 10 Sprague Dawley rats were given i.p. doxorubicin (4 mg/kg) during 60 min combined with no pressure (control), 10, 20 and 30 mm Hg pressures. During the course of i.p. chemotherapy, peritoneal fluid and blood were sampled. Two other groups of 10 rats received the same dose of i.p. doxorubicin during 10 min combined with no pressure and 30 mm Hg pressure. At the end of experiments animals were sacrificed and tissue samples were collected. Doxorubicin concentrations in peritoneal fluid, plasma and tissues were determined by HPLC. Pharmacokinetic studies showed that increased intra-abdominal pressures of 10, 20 and 30 mm Hg did not alter peritoneal fluid AUCs, the plasma AUCs and the peak ratios of i.p. doxorubicin when compared to the control group (no pressure). A subset analysis of high intra-abdominal pressure groups (20 and 30 mm Hg) versus control group showed statistically significant differences in peritoneal fluid AUCs, plasma AUCs and AUC (peritoneal fluid/plasma) ratios. For all groups, the highest tissue concentrations of doxorubicin were found in tissues associated with the parietal peritoneum: the bladder, the abdominal wall and the diaphragm. After 10 min of i.p. chemotherapy, the group treated with 30 mm Hg pressure showed a significant increase of doxorubicin concentrations in these tissues as compared to the control group. This significant increase of tissue doxorubicin concentrations was not found after 60 min of pressure with i.p. chemotherapy; prolonged intra-abdominal pressure was associated with a high incidence of intestinal ischemia. In conclusion, intra-abdominal pressure of 20 and 30 mm Hg significantly decreased the AUC ratios of i.p. doxorubicin but concomitantly increased tissue uptake of doxorubicin in bladder, diaphragm and abdominal wall during the first 10 min of i.p. administration. These findings may have significance in the design of improved strategies to increase tissue concentrations of chemotherapy delivered by an i.p. route.     

Menadione induces changes in the membrane electrical properties associated with downregulation of insulin receptors in human erythrocytes

BACKGROUND AND OBJECTIVE: To investigate the course of the intraocular pressure (IOP) in nonglaucomatous patients with pseudoexfoliation (PSX) syndrome after cataract surgery. PATIENTS AND METHODS: In a prospective age-matched controlled clinical study, 23 consecutive patients with PSX were studied and compared with a control group of 23 patients. The IOP was measured by applanation tonometry preoperatively, and postoperatively on day 1, after 4 weeks, and after 6 months. All patients were operated on with a self-sealing 7-mm scleral tunnel incision, phacoemulsification, and posterior chamber intraocular lens (IOL) implantation. RESULTS: Preoperatively the IOP was similar between both groups (P = .962). At the first postoperative day the IOP was below 22 mm Hg in all cases. After 4 weeks and 6 months a mean decrease of 3.88 mm Hg (P = .001) in the control group and of 3.15 mm Hg (P = .002) in the PSX group was observed; this difference was not statistically significant (P = .543). CONCLUSIONS: At 1 day postoperatively no pressure increase was observed in the eyes with PSX after scleral tunnel incision and phacoemulsification. Six months after cataract extraction with IOL implantation, the tension level decreased in the presence of PSX similarly as in normal eyes.     

Sodium ramping in hemodialysis: a study of beneficial and adverse effects

Sodium ramping has been introduced as a technique to decrease side effects occurring during hemodialysis. We studied sodium ramping in 414 dialysis sessions in 23 patients by randomizing 2-week blocks of dialysis to either steady dialysate sodium of 140 mEq/L, linear sodium ramping during dialysis from 155 mEq/L to 140 mEq/ L, or stepwise ramping (sodium of 155 mEq/L for 3 hours and 140 mEq/L for 1 hour). We studied the number and severity of hypotensive and hypertensive episodes. A hypotensive episode was defined as an abrupt decline of systolic blood pressure of more than 50 mm Hg, a decrease in blood pressure accompanied by symptoms requiring intervention, or systolic blood pressure of less than 90 mm Hg even without symptoms. A hypertensive episode was defined as a sudden increase in systolic blood pressure of over 30 mm Hg. We also recorded other side effects (headache, cramps, nausea, vomiting, dizziness, thirst, fatigue, weight gain, and blood pressure) during, immediately after, and between dialysis sessions. There was no major difference between the two ramping protocols, but compared with standard dialysis, both decreased total number of side effects from 4.0 to 3.0 (P = 0.057); the number of hypotensive episodes decreased from 1.3 to 0.7 (P = 0.036). The lowest blood pressure was 114/66 mm Hg during control and 123/69 mm Hg during ramping (P < 0.0001). The frequency of cramps during dialysis decreased from 0.9 to 0.5 (P = 0.006). There was no difference in headache, nausea, or vomiting. The number of hypertensive episodes increased from 0.045 to 0.086 during ramping (P = 0.125). Of 23 patients, only five (22%) had a marked decrease in symptoms; two of the three most symptomatic patients showed no significant improvement. Between dialysis sessions, patients complained of more fatigue and thirst (P < 0.0001 and P = 0.0028, respectively), and interdialytic weight gain following ramping was 5.1% of body weight compared with 4.4% without ramping (P < 0.0001). Blood pressure also increased following ramping, from 143/79 mm Hg to 152/81 mm Hg (P = 0.001). Ramping can decrease the overall number of side effects, but increases interdialytic symptoms, weight gain, and hypertension. In most instances, it simply changes the time the side effects occur. Only 22% of patients have significant benefit. These patients can be identified only through trial and error, as no model of these patients can be created.     

Effect of flush-perfusion on vascular endothelial and smooth muscle function

BACKGROUND: The aim of this study was to investigate how much perfusion pressure an artery can tolerate without significant loss of endothelium-dependent relaxation (EDR) and vascular contractility. METHODS: The abdominal aortas of 396 Sprague-Dawley rats were used. One hundred twenty aortas were flush-perfused for 1 or 5 minutes with cold St. Thomas' Hospital cardioplegic (STHC) solution or with the same solution but modified by the addition of 3.5% dextran 40. Three perfusion pressures were tested: 50, 100, and 150 mm Hg. Two hundred eighty vessels were subjected to pressures of 50, 150, or 300 mm Hg using saline or STHC solution at 22 degrees C or STHC solution at 4 degrees C, for 10 or 60 seconds. The vessels were investigated in organ baths. Contractility was tested with the thromboxane analogue U-46619, acetylcholine was used to investigate EDR, and papaverine to elicit endothelium-independent relaxation. RESULTS: Flush-perfusion with cold STHC solution for 5 minutes at a perfusion pressure of 50 or 100 mm Hg affected neither contractility nor EDR. Vessels exposed to a flush-perfusion pressure of 150 mm Hg for 1 or 5 minutes lost 39% (p < 0.001) and 53% (p < 0.001) of their contractility, respectively. Flush-perfusion at 150 mm Hg for 1 minute did not affect EDR, whereas 5 minutes' perfusion caused a reduction of 7% (p < 0.05). A repetition of these experiments using STHC solution with 3.5% dextran 40 added gave no significantly different results. The impairment in contractility and EDR seen after perfusion at 150 mm Hg for 5 minutes disappeared after transplantation and reperfusion for 7 days. The vessels could be distended with saline or STHC solution at a pressure of 150 mm Hg without affecting contractility at 22 degrees C. At 4 degrees C, however, this pressure was harmful to contractility. Distention at a pressure of 300 mm Hg almost abolished contractility and 7 days after transplantation there had not yet been any recovery of contractility, but 30 days after transplantation the grafts had regained their normal contractility. CONCLUSIONS: Cold STHC solution, with or without dextran 40, can be used with a perfusion pressure of 100 but not 150 mm Hg without impairing EDR or vascular smooth muscle function.     

Ruptured pseudoaneurysm of the splenic artery. A complication of chronic pancreatitis

HISTORY AND FINDINGS: A pale looking 33-year-old man with a history of perforated gastric ulcer and pancreatitis with surgically drained pseudocyst was admitted because of painless anal bleeding. Heart rate was 100/min, blood pressure 90/60 mm Hg. INVESTIGATIONS: Haemoglobin concentration (6.3 g/dl) and RBC count (2.4 mill./microliters) indicated anaemia due to bleeding. Sonography and computed tomography demonstrated chronic calcifying pancreatitis and thrombosis of splenic and mesenteric veins. There were grade 1 oesophageal varices on endoscopy. The source of bleeding was found by coloscopy to be a submucous pulsating tumour in the region of the left flexure, which on angiography was an aneurysm of the splenic artery. TREATMENT AND COURSE: The pseudoaneurysm of the splenic artery, which had perforated into the colon, was resected together with a partial pancreas excision and splenectomy. There were no complications and the patient was discharged symptom-free after 15 days, and there had been no further bleeding 6 months later. CONCLUSION: Pseudoaneurysm of a visceral artery is a rare, but life-threatening, complication of pancreatitis. Treatment options are operation and/or interventional catheter embolisation.     

The effect of changes in perfusion pressure on uteroplacental blood flow in the pregnant rabbit

The effect of perfusion pressure on uteroplacental blood flow was determined in pregnant rabbits utilizing the radioactive microsphere method. Control mean arterial pressure, 93 mm Hg +/- 2.6 SEM, was raised by carotid ligation to 109 +/- 4.1 mm Hg and then reduced with antihypertensive drugs to 74 +/- 1.3 mm Hg. Over this range of pressure there was no significant change in cardiac output, 605 +/- 36, 523 +/- 37, and 540 +/- 39 ml/min; or uteroplacental blood flow, 30 +/- 3.2, 27 +/- 5.2, and 29 +/- 4.5 ml/min, respectively. When prostaglandin synthesis was inhibited with either indomethacin or meclofenamate (2 mg/kg), uterine vascular resistance was higher but maintenance of uteroplacental flow occurred over a perfusion pressure of 89 +/- 6.7-115 +/- 9.3 mm Hg. With more severe hypotension induced with trimethaphan, control arterial pressure fell from 92 +/- 2.4 to 39 +/- 0.9 mm Hg, cardiac output fell from 514 +/- 17 to 407 +/- 22 ml/min (P less than 0.025) and uteroplacental blood flow fell from 6.1 +/- 0.9 to 2.5 +/- 0.9% of cardiac output (P less than 0.05), which represented an absolute fall from 32.4 +/- 5 to 10.6 +/- 3 ml/min (P less than 0.025). There was no significant change in renal blood flow expressed as percentage of cardiac output, 14.9 +/- 2 and 13 +/- 1.5%, or in absolute flow, 75 +/- 7.7 and 54 +/- 7 ml/min with trimethaphan-induced hypotension. These studies indicate that uteroplacental blood flow is maintained relatively constant over a range of perfusion pressure of 60-140 mm Hg in both normal and prostaglandin-inhibited pregnant rabbits. However, with reduction in pressure to 36-42 mm Hg, uteroplacental blood flow falls, expressed as a percentage of cardiac output and in absolute flow.     

A second phase III multicenter placebo controlled study of 2 dosages of modified release tamsulosin in patients with symptoms of benign prostatic hyperplasia. United States 93-01 Study Group

PURPOSE: In a double-blind, phase III clinical trial we evaluate the safety and efficacy of 0.4 and 0.8 mg. tamsulosin daily for the treatment of patients with symptoms of moderate to severe benign prostatic hyperplasia. MATERIALS AND METHODS: Patients meeting the basic requirements of the study underwent a 4-week single-blind placebo evaluation period. A total of 735 patients were randomized to double-blind therapy with tamsulosin or placebo. Treatment duration was 13 weeks. Efficacy and safety were evaluated at 5 visits during the double-blind treatment period. RESULTS: When efficacy data between baseline and end point were compared there was a significant reduction in total American Urological Association symptom score (25%) in each tamsulosin group compared with placebo (p = 0.01) and the percentage of patients with a 30% or more reduction in peak urinary flow rate was significantly greater in the tamsulosin versus placebo group (p <0.05). Improvements in American Urological Association symptom scores and maximum flow rate occurred at 1 week of treatment. None of the patients experienced a first dose effect. There were no significant changes in blood pressure on standing at any visit during the study except for a decrease in systolic blood pressure of 20 mm. Hg or more between the 0.8 mg. dose and placebo groups at visit 4 (p = 0.036). Positive orthostatic tests were significantly more frequent in the 0.8 mg. group compared with placebo at visit 4 (p = 0.012). The treatment groups did not differ significantly in incidence of electrocardiogram abnormalities at each post-baseline visit and at end point. CONCLUSIONS: Tamsulosin was safe and effective, and clinically and statistically superior to placebo in relieving symptoms of benign prostatic hyperplasia in men with moderate to severe symptoms at baseline. There was no evidence of a first dose effect and no clinically significant orthostatic hypertension. In addition, response to treatment was rapid.