Persistent Clinical Improvement Research Articles

Bortezomib-based treatment for relapsed and refractory angioimmunoblastic T-cell lymphoma: Case report and literature review

Angioimmunoblastic T-cell lymphoma (AITL) is a distinct peripheral T-cell lymphoma (PTCL) subtype, accounting for 15-20% of PTCL and 2% of all non-Hodgkin lymphoma (NHL), with a poor prognosis. In the present study, we describe a 76-year-old patient with AITL who failed to respond to conventional chemotherapy but responded to bortezomib-based treatment and demonstrated persistent clinical improvement at the 18-month follow-up. These data suggest that bortezomib-based treatment may be a reliable, safe and effective alternative for treating relapsed/refractory AITL.

Left ventricular endocardial pacing improves the clinical efficacy in a non-responder to cardiac resynchronization therapy: role of acute haemodynamic testing

Recently, emphasis has been shifted from patient selection to more optimal pacing sites in non-responders to cardiac resynchronization therapy (CRT). We present a patient who was a non-responder during both acute haemodynamic testing at implant as well as clinically thereafter. After first demonstrating acute haemodynamic improvement using LV d P /d t max during a temporary left ventricular (LV) endocardial pacing setup, a permanent LV endocardial lead was transseptally implanted with substantial and persistent clinical improvement.

Endoscopic third ventriculostomy for obstructive hydrocephalus due to intracranial hemorrhage with intraventricular extension

Object Endoscopic third ventriculostomy (ETV) is well accepted for obstructive hydrocephalus of various etiologies. Nevertheless, it is seldom considered in intracranial hemorrhage even in cases involving obstruction of the CSF circulation. Methods Between May 1993 and April 2008, 34 endoscopic procedures were performed for hemorrhage-related obstructive hydrocephalus with an intraventricular component. All patients were prospectively followed up. Special attention was paid to presurgical clinical status, type of hemorrhage, type of surgery, postsurgical clinical status, postsurgical ventricular size, and necessity of ventriculoperitoneal shunt implantation. Results An ETV was performed for treatment of obstructive hydrocephalus due to intracranial hemorrhage in 34 patients (15 male, 19 female; mean age 60.8 years [range 3 months-83 years]). Hydrocephalus was caused by 17 cerebellar, 6 thalamic, 5 intraventricular, 3 basal ganglia, 2 subarachnoid, and 1 pontine hemorrhage. Thirty-three patients (97.1%) presented with impaired consciousness. Intraventricular blood was present in all cases. In 16 cases (47.1%), blood clots had to be evacuated to achieve access to the third ventricle floor. The mean operation time was 58.2 minutes (range 25-120 minutes). Three complications occurred (rate of 8.8%) with 2 being asymptomatic (5.9%) and 1 being transient (2.9%). There was no procedure-related permanent morbidity, and no procedure-related mortality. After surgery, there was clinical improvement in 17 cases (50.0%) and radiological evidence of improvement in 22 cases (64.7%). Two patients required postoperative ventriculoperitoneal shunting (5.9%). Seven patients died of hemorrhage while in the hospital (20.6%), and another 4 died during follow-up (11.8%). Fifteen patients (44.1%) showed a persistent clinical improvement at the final follow-up (mean 12.2 months after surgery). Conclusions Endoscopic third ventriculostomy represents a safe treatment option in intraventricular hemorrhage-related obstructive hydrocephalus yielding similar results as an external drainage but with less risk of infection and a very low subsequent shunt placement rate. In cases with a predominant obstructive component, ETV should be considered in hydrocephalus due to intracerebral hemorrhage. However, performing an ETV with a blurred field of vision and distorted ventricular anatomy is a challenge for any endoscopic neurosurgeon and should be reserved for experienced neuroendoscopists.

Two vascular arteriovenous malformations with left-to-right shunting and right-heart failure in a single patient

Arteriovenous malformations may lead to right-heart failure in cases of hemodynamically significant left-to-right shunting. Here, we report the case of a 37-year-old female who presented with congestive heart failure related to an isolated anomalous connection of the left pulmonary vein to the left brachiocephalic vein (partial anomalous pulmonary venous connection). After successful reconnection to the left appendage and clinical improvement, the patient once again developed progressive signs of heart failure. Several arteriovenous malformations were identified in the liver as the underlying cause of the patient's high-output heart failure, and the patient was retrospectively diagnosed with hereditary hemorrhagic telangiectasia. Target embolization led to right-ventricular remodeling, and persistent clinical improvement. To our knowledge, this is the first report of two rare AV-malformations with left-to-right shunting and progressive right-heart failure in a single individual.

Double-balloon enteroscopy in Crohn’s disease patients suspected of small bowel activity: findings and clinical impact

It is estimated that 10-30% of patients with Crohn's disease (CD) have small bowel (SB) involvement, but the exact frequency and clinical relevance of these findings is unknown. Double-balloon enteroscopy (DBE) enables endoscopic visualization of the SB. In this study we evaluated whether DBE is a feasible technique for detection of CD localized in the SB in CD patients with clinical suspicion of SB lesions and whether these findings have clinical impact. Retrospectively we analyzed 52 DBE procedures in 40 CD patients (16 males, mean age 40 years, mean duration of CD 15 years). Included patients had clinical suspicion of small bowel CD activity, including persistent abdominal discomfort (n = 27), iron deficiency anemia (n = 9) and/or hypomagnesemia (n = 4). Active small bowel CD was found in 24 (60%) patients, leading to a change in therapy in 18 patients (75%). After a mean follow-up of 13 months, 15 (83%) had persistent clinical improvement with a significant drop of mean CDAI from 178 to 90, after a mean follow-up of 13 months. DBE is a useful diagnostic tool for the evaluation of SB lesions in CD patients. The significance of these findings is emphasized by the fact that adjustment of therapy in the majority of these patients leads to significant and sustained clinical improvement.

Abstract No. 26: Percutaneous Stenting across IVC Filters During Recanalization and Reconstruction of Chronic IVC and Iliac Vein Occlusions in 15 Symptomatic Patients

Abstract No. 26: Percutaneous Stenting across IVC Filters During Recanalization and Reconstruction of Chronic IVC and Iliac Vein Occlusions in 15 Symptomatic Patients

The role of infection in irritable bowel syndrome

A clinically distinct subset of Irritable Bowel syndrome (IBS) could be induced or exaggerated by bowel infection that is called post-infective IBS (PI-IBS) which is characterized by diarrhea predominant symptoms with less psychiatric illness. The purpose of this work was to study whether some bowel infections contribute to the pathogenesis of IBS and whether the treatment of such infections reduces IBS symptoms. 100 patients with symptoms suggestive of IBS according to Rome II Criteria were chosen from Internal Medicine outpatient clinic-Al Hussein university hospital. They were 64 females and 36 males, aged 18-52 years old with mean age 38,2  3,6 years. They were submitted to: full clinical examination and frequent stool examinations (direct smear and culture) before, soon after and six months after administration of drug therapies for common stool-positive associated bowel infections (diloxanide for E. histolytica, metronidazole for Giardia lamblia, Ketoconazole for Candida, ciprofloxacin for Salmonella and neomycin for Pseudomonas). Results obtained showed that 24% of patients had diarrhea predominant symptoms, 13 patients (54%) out of them had history suggestive of acute gastroenteritis. 80 patients had initial positive stool examination and continued the post treatment six months follow up study. Out of them, 13 patients had stool positive for Salmonella typhi mixed with E. histolytica; ten of them (76.9%) showed a statistically significant persistent clinical and laboratory improvement after ciprofloxacin therapy (P < 0.01). So Salmonella typhi may be implicated in IBS pathogenesis. Six patients showed isolated Giardia lamblia infection; four of them (66.7%) showed a statistically significant persistent clinical and laboratory improvement after metronidazole thereby (P < 0.05). Giardia lamblia parasite may be considered in triggering or exaggerating IBS symptoms. 24 patients had isolated E. histolytica infection; only one of them (4.2%) showed sustained clinical and Laboratory improvement after diloxanide therapy -statistically insignificant result- (P > 0.05). This finding makes the correlation between E. histolytica infection and IBS is unlikely. 20 patients had isolated Candida overgrowth on stool examination; eight of them (40%) showed a statistically significant clinical and laboratory improvement after Ketoconazole therapy (P < 0.05). Therefore Candida overgrowth may induce or exaggerate IBS symptoms. Finally, no growth was noticed for shigella sp. or E. coli, this may exclude the role of such organisms in IBS pathogenesis.

Survival of patients removed from the heart transplant waiting list

Objective End-stage heart failure has been associated with high mortality in the absence of transplantation. We evaluated the outcome of patients receiving optimal medical therapy who were removed from the cardiac transplant waiting list to determine survival and predictors of mortality. Methods We performed a retrospective review of 27 patients removed from the cardiac transplant waiting list from 1999 to 2001 at our institution. Results Mean age was 53 ± 11 years; 16 of the patients were male. Status was IB in 3 cases and II in 24. Median time on the list was 32 months, and median follow-up was 2.9 years. Patients were removed from the transplant list because of either clinical improvement (group A, n = 18) or deterioration (group B, n = 9). In group A, 13 patients had improved functional status and 10 were in New York Heart Association class 1 or 2; 16 had improved echocardiographic left ventricular function. Survivals at 3 years were 100% in group A and 44% in group B ( P < .01). Conclusion Patients with end-stage heart failure who have clinical response to medical therapy have excellent 3-year survival. These data suggest the necessity of close evaluation of patients waiting for transplantation, with a low threshold for inactivation if persistent clinical improvement is observed.

Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study

Continuous intravenous epoprostenol improves exercise capacity, haemodynamics, and survival in severe primary pulmonary hypertension. Pulmonary hypertension can also be life-threatening in patients with connective tissue diseases. In a prospective open monocentre uncontrolled study, the effects of epoprostenol were evaluated in patients with severe pulmonary hypertension secondary to connective tissue diseases who were unresponsive to oral vasodilators (including calcium channel blockers) and continued to be in the New York Heart Association (NYHA) functional class III or IV despite conventional medical therapy. Seventeen patients received epoprostenol administered by a portable infusion pump associated with conventional therapy (oral anticoagulants, diuretics, supplemental oxygen). During the first six weeks of therapy, two (12%) patients died, of pulmonary oedema (n = 1) and severe sepsis (n = 1). In the fifteen remaining subjects, clinical and haemodynamic parameters improved significantly at six weeks. These patients were subsequently monitored for 80+/-48 (range 14-154) weeks after initiation of epoprostenol. Five (33%) patients died, of right heart failure (n = 2), severe sepsis (n = 2) or syncope (n = 1) and two patients were successfully transplanted 24 and 52 weeks after initiation of epoprostenol. Seven of the remaining eight patients had a persistent clinical improvement. Short-term epoprostenol therapy is effective in some patients with connective tissue diseases as demonstrated by better clinical status and haemodynamics at six weeks. However, this study reports several cases of early and late major complications including severe sepsis and pulmonary oedema. Additional information is needed to evaluate the benefit: risk ratio of long-term epoprostenol therapy in pulmonary hypertension secondary to connective tissue diseases.

Balloon aortic valvuloplasty in elderly patients at high risk for surgery, or inoperable

Although aortic valve replacement is undoubtedly the treatment of choice for aortic valve stenosis, balloon aortic valvuloplasty may represent the only possible treatment for some frail elderly patients who may have additional medical problems. We evaluated immediate and 1-year results of balloon aortic valvuloplasty in 86 patients > or = 80 years with severe aortic stenosis. Mean age was 84 +/- 3 years. Forty-four % were 85 years or older. Mean gradient decreased from 68 to 26 mm Hg and valve area increased from 0.53 to 0.96 cm2 (P<0.05). There were two per-procedural deaths. No local vascular complication was observed. During the follow-up (13 +/- 9 months), 27 patients died, four had repeat balloon aortic valvuloplasty and eight underwent aortic valve replacement. Persistent clinical improvement was observed in 78% of the surviving patients. One-year actuarial survival rate was 73%. Balloon aortic valvuloplasty appears to be a safe and valuable technique in cases where surgery cannot be performed or carries a very high risk.

Balloon mitral commissurotomy for mitral restenosis after surgical commissurotomy

Balloon mitral commissurotomy (BMC) was performed in 113 patients. Of these patients, 27 (24%) (25 women and 2 men, aged 49 ± 13 years) had recurrent mitral stenosis 13 ± 6 years (range 5 to 29) after surgical Commissurotomy. Eleven patients (41%) were considered at high risk for surgery. BMC resulted in an increase in mitral valve area from 1.1 ± 0.3 to 1.9 ± 0.7 cm 2 (p < 0.0001), and a decrease in mean mitral gradient from 16 ± 7 to 6 ± 3 mm Hg (p < 0.0001). An optimal result of BMC (increase in valve area ≥25% with a post-BMC valve area ≥1.5 cm 2) was obtained in 18 patients (67%). The results did not differ from those observed in the 86 patients of our entire series without prior surgical Commissurotomy. Patients with an optimal result of BMC had a more recent surgical Commissurotomy and lesser morphologic alterations of the mitral valve than did those with a nonoptimal result. Patients with echocardiographic scores <10 had an 80% success rate of BMC; however, this rate decreased to 29% for those with scores ≥10. One patient (4%) died from a cerebrovascular accident. Clinical follow-up at 1 year showed persistent clinical improvement in 89% of patients with an optimal result of BMC; 72% were in New York Heart Association class I and 17% in class II. Thus, BMC is a safe and effective short- and long-term procedure for patients with mitral restenosis after surgical commissurotomy; because of its percutaneous approach, avoiding the risks associated with a second thoracotomy, BMC can be considered the treatment of choice in these patients.

Combined percutaneous mitral and aortic balloon valvuloplasty

Between August 1987 and November 1988, combined mitral and aortic balloon valvuloplasty was performed in 10 patients (mean age 42 ± 9 years), all of whom had symptomatic mitral and aortic stenosis, the procedure was performed using a transarterial approach with a multiballoon catheter and an exteriorized intracardiac long guidewire circuit. The procedure could be considered successful in 9 patients where significant increases in the mean mitral (0.97 ± 0.19 to 1.80 ± 0.26 cm 2) and aortic (0.63 ± 0.18 to 1.15 ± 0.32 cm 2) areas were achieved. Severe mitral regurgitation that required surgery developed in 1 patient in the following 24 hours. Femoral vascular surgery was necessary in 1 patient. Mid-term follow-up was available in 8 patients for a period averaging 8 ± 3 months. The 9 patients in whom the procedure was successful showed persistent clinical improvement in functional class- Doppler echocardiography showed 2 cases of aortk restenosis and none of mitral restenosis. Combined mitral and aortic balloon valvuloplasty could be a valid alternative treatment in selected patients with both mitral and aortic rheumatic stenosis. Further experience and longterm hemodynamic follow-up are necessary to define the role of this mode of treatment.

Percutaneous balloon valvuloplasty in patients with severe aortic stenosis and low ejection fraction. Immediate results and 1-year follow-up.

The efficacy, morbidity, and 1-year follow-up of balloon aortic valvuloplasty in patients with low ejection fraction (less than 40%) were studied on a consecutive series of 55 patients (mean age, 77 years) treated from September 1985 to February 1987. Because of their age (20 patients greater than 80 years old), poor left ventricular function, and associated diseases, 45 patients were definitely not surgical candidates. Balloon dilatation with 15-23-mm diameter balloon catheters decreased the transvalvular gradient from 66 +/- 24 to 28 +/- 14 mm Hg (p less than 0.001) and increased the valve area from 0.47 +/- 0.15 to 0.83 +/- 0.27 cm2 (p less than 0.001). Immediately after dilatation, ejection fraction mildly increased from 29 +/- 7% to 34 +/- 9% (p less than 0.001) in 38 patients who had undergone a second left ventricular angiogram after dilatation. No significant change in the degree of aortic regurgitation was found after the procedure. Three patients died in hospital (femoral arterial complications in two, septicemia in one). Immediate clinical improvement was noted in 80% of the patients. During the follow-up (mean, 11 months), 22 patients died (heart failure in 15 patients, sudden death in five patients, myocardial infarction in one patient, cancer in one patient). Thirty patients survived, 21 with persistent clinical improvement. Repeat cardiac catheterization was performed at 6 months in 20 patients, of whom eight had recurrence of symptoms. Nine patients had restenosis: their hemodynamic indexes had returned to prevalvuloplasty values.(ABSTRACT TRUNCATED AT 250 WORDS)

Use of ketoconazole in the treatment of Cushing's syndrome.

The therapeutic value of ketoconazole for long term treatment of patients with Cushing's syndrome was studied. Seven patients with Cushing's disease and one with an adrenal adenoma received 600-800 mg/day ketoconazole for 3-13 months. Plasma ACTH, cortisol, and dehydroepiandrosterone sulfate levels and urinary cortisol, 17-ketosteroid, and tetrahydro-11-deoxycortisol excretion were determined periodically during the treatment period. Plasma ACTH and cortisol responses to CRH stimulation were determined before and during treatment. Rapid and subsequently persistent clinical improvement occurred in each patient; plasma dehydroepiandrosterone sulfate and urinary 17-ketosteroid and cortisol excretion decreased soon after the initiation of treatment, subsequently remaining normal or nearly so throughout the treatment period. Urinary tetrahydro-11-deoxycortisol excretion increased significantly. Plasma cortisol levels decreased. Plasma ACTH levels did not change, and individual plasma ACTH and cortisol increments in response to CRH were comparable before and during treatment. The cortisol response to insulin-induced hypoglycemia improved in one patient and was restored to normal in another. The seven patients tested recovered normal adrenal suppressibility in response to a low dose of dexamethasone during ketoconazole treatment. Ketoconazole is effective for long term control of hypercortisolism of either pituitary or adrenal origin. Its effect appears to be mediated by inhibition of adrenal 11 beta-hydroxylase and 17,20-lyase, and it, in some unknown way, prevents the expected rise in ACTH secretion in patients with Cushing's disease.

Late results following operative repair for celiac artery compression syndrome

The clinical significance of celiac artery compression by the median arcuate ligament of the diaphragm remains unsettled. The controversy stems from an undefined pathophysiologic mechanism and the existence of celiac compression in asymptomatic patients. This study was therefore conducted to evaluate the late results of operative therapy among our patients and possibly to identify parameters that might correlate with sustained symptom relief. Among 51 patients (12 men and 39 women) (mean age 47 years) who underwent operative treatment for symptomatic celiac artery compression, 44 (86%) were available for late follow-up. Their clinical status was determined between 1 and 18 years postoperatively (mean 9.0 years) by patient interview (36) or chart review (7). Operative treatment consisted of celiac axis decompression only (16 patients), celiac decompression and dilatation (17 patients), or celiac decompression and reconstruction by primary reanastomosis or interposition grafting (18 patients). Sustained symptom relief occurred more often with a postprandial pain pattern (81% cure), age between 40 and 60 years (77%), and weight loss of 20 pounds or more (67%). A negative correlation with clinical improvement was demonstrated for an atypical pain pattern with periods of remission (43% cure), a history of psychiatric disorder or alcohol abuse (40%), age greater than 60 years (40%), and weight loss of less than 20 pounds (53%). Eight of 15 patients (53%) treated by celiac decompression alone remained asymptomatic at late follow-up in contrast to 22 of 29 patients (76%) treated by celiac decompression plus some form of celiac revascularization. Late follow-up arteriograms (18 studies) showed a widely patent celiac artery in 70% of asymptomatic patients but a stenosed or occluded celiac axis in 75% of symptomatic patients. These findings suggest that persistent clinical improvement in patients with symptomatic celiac axis compression can be achieved by an operative technique that ensures celiac axis patency. Although some clinical features are identified that correlate with long-term benefit, reliable diagnosis of the symptomatic patient awaits definition of the pathophysiologic mechanisms involved in this syndrome.

Dilation angioplasty of congenital or operative narrowings of venous channels.

Balloon dilation angioplasty was attempted in 10 infants and children with severe congenital or operative "venous" obstructions. In five children the obstructions were "vena caval" and followed repair for transposition of the great vessels (four patients) or orthotopic liver transplantation (one patient). In the four patients with fixed vena caval or baffle obstructions, balloon angioplasty was successful in relieving the obstruction, decreasing the average gradient (16.0 to 4.5 mm Hg), and increasing the average diameter (3.0 to 8.9 mm) of the obstructed site. One child died 1 week later from an unrelated cerebral hemorrhage; the three survivors have had persistent clinical and angiographic improvement. The fifth child had severe systolic narrowing of the superior baffle limb caused by marked tricuspid regurgitation, which ballooned the superior limb of the baffle against the atrial roof. Angioplasty was unsuccessful in relieving this type of obstruction, which resolved with tricuspid valve replacement. Of the five infants with obstructed pulmonary veins, three had congenitally narrowed vessels associated with total anomalous pulmonary venous connection, one had acquired stenosis, and one had postoperative obstruction after repair of a mixed type of total anomalous pulmonary venous connection. Dilation was unsuccessful in all five patients, but for different reasons: in the congenitally narrowed veins, the waist in the balloon could not be eliminated, even with high dilating pressures; in the infant with acquired stenosis, the vein stretched but did not tear at low dilating pressures; and in the postoperative obstruction, angioplasty increased the diameter of the obstruction but did not increase flow to the affected lung.(ABSTRACT TRUNCATED AT 250 WORDS)

The renin-angiotensin system in refractory heart failure: clinical, hemodynamic and hormonal effects of captopril and enalapril.

Studies using a competitive inhibitor of angiotensin II (saralasin) or converting enzyme inhibitors (teprotide, captopril, enalapril) have established that the renin-angiotensin system participates in the control of vascular tone in congestive heart failure both in experimental settings and in patients. In man, the marked decrease in left ventricular filling pressure and the variable increase in stroke volume induced by renin-angiotensin blockade suggests that angiotensin II actively constricts venous as well as arteriolar vascular beds. Captopril, in doses of 25 to 150 mg p.o. TID, maintains its efficacy during chronic administration with persistent clinical and hemodynamic improvement as well as increased exercise tolerance. In our experience, enalapril, 10 mg p.o., improves cardiac function within 4 to 6 h as reflected by a 30% decrease in left ventricular filling pressure, a 28% increase in stroke volume in the face of unchanged heart rate. Clinical improvement, enhanced exercise tolerance and characteristic hormonal responses suggest that enalapril also maintains its efficacy during long-term treatment. Chronic angiotensin II converting enzyme inhibition appears to be a major advance in the treatment of patients with severe congestive heart failure, refractory to digitalis and diuretics.