Dopamine transporter imaging and the effects of deep brain stimulation in patients with Parkinson's disease.

PURPOSE: Single-photon emission computed tomography (SPECT) with [123I]FP-CIT is a marker for loss of presynaptic dopamine transporters in the striatum in Parkinson's disease (PD). We used [123I]FP-CIT SPECT in order to evaluate binding to the dopamine transporter before and after neurosurgical treatment with bilateral stimulation in the subthalamic nucleus (STN). METHODS: Thirty-five patients with levodopa-responsive PD were examined with [123I]FP-CIT SPECT pre-operatively (baseline scan: mean 3 months before surgery), and 3 and 12 months after surgery. RESULTS: Pre-operatively, all patients already had substantial signs of severe nigrostriatal neuronal loss as determined from the [123I]FP-CIT SPECT scans. One year after surgery the specific [123I]FP-CIT binding to the striatum was significantly reduced by 10.3% compared with the pre-operative baseline scan. The mean time span from the baseline scan before surgery to the follow-up scan 1 year after surgery was 16.2 months. Hence, the rate of reduction equals a mean annual reduction of 7.7%. A comparable control group of patients with PD who did not undergo surgery was also examined longitudinally. In this group the specific binding of [123I]FP-CIT was reduced by 6.7% per year. CONCLUSION: The specific binding of [123I]FP-CIT was reduced equally in the STN-stimulated patients and a group of non-operated PD patients with advanced disease. Our study does not support the notion that electrode implantation and STN stimulation exert a neuroprotective effect by themselves.

Iridoid glucosides from Myxopyrum smilacifolium.

From a single leaf of a herbarium sheet of Myxopyrum smilacifolium was isolated the iridoid glucosides myxopyroside (1) and its 6-O-acetyl-7-O-(E/Z)-p-methoxycinnamoyl esters (2/3) of dimethyl forsythide. The presence of these compounds indicates a close relationship with the genus Nyctanthes, from which similar compounds have earlier been reported. This finding corroborates relationships recently found within the family Oleaceae by modern gene sequencing techniques.

Chemotaxonomy of Plantago. Iridoid glucosides and caffeoyl phenylethanoid glycosides.

Data for 34 species of Plantago (Plantaginaceae), including subgen. Littorella (= Littorella uniflora), have been collected with regard to their content of iridoid glucosides and caffeoyl phenylethanoid glycosides (CPGs). In the present work, 21 species were investigated for the first time and many known compounds were found together with three new iridoid glucosides. Of these, arborescoside and arborescosidic acid, both of the uncommon type with an 8,9-double bond, were present in several species, while 6-deoxymelittoside was found only in P. subulata. The known compounds deoxyloganic acid, caryoptoside and rehmannioside D were isolated from the genus for the first time. The earlier reported occurrence of sorbitol in the family was confirmed, and this compound was shown by NMR spectroscopy to be the main sugar in the three species investigated for this. The combined data show that CPGs are present in all species investigated. With regard to the iridoids, the distribution patterns showed a good correlation with the classification of Rahn. Thus, aucubin is typical for the whole genus, while bartsioside and catalpol as well as 5-substituted iridoids are each characteristic for a subgenus in the family. Finally, the close relationship between Plantago and Veronica suggested by chloroplast DNA sequence analysis. could be corroborated by the common occurrence of the rare 8,9-unsaturated iridoids in these two genera.

Conversion of the iridoid glucoside antirrhinoside into 3-azabicyclo[3.3.0]octane building blocks.

The iridoid glucoside antirrhinoside (1) was transformed into polysubstituted 3-azabicyclo[3.3.0]octanes 3, 12, and 13 in 4 to 5 steps. Ozonolysis of the diacetonide of 1 and of its 7-deoxy-derivative 8 afforded cyclopentanoids 2 and 10, respectively. Conditions for the selective conversion of 2 and 10 into the corresponding ditosylates 4 and 11 were investigated. Cyclization of 4 and 11 was achieved with benzylamine and 2-methoxybenzylamine to yield bicyclic pyrrolidines 3, 12, and 13. Additional building blocks 14 and 15 were obtained by selective deprotection of the N-benzyl and isopropylidene moieties in 12 and 13, respectively.

Iridoid glucosides from Phlomis tuberosa L. and Phlomis herba-ventis L.

A new iridoid glucoside, 5-desoxysesamoside, was isolated from Phlomis tuberosa L. (Lamiaceae) together with three known iridoid glucosides sesamoside, shanziside methyl ester and lamalbid. Lamiide was found in P. herba-ventis ssp. pungens in high concentrations.

A 9-hydroxyiridoid isolated from Junellia seriphioides (Verbenaceae).

[structure: see text] An unusual iridoid glucoside, namely 9-hydroxy-8-epihastatoside (1), was isolated from Junellia seriphioides (Verbenaceae), together with the known compounds auroside (2), pulchelloside I (3), and 8-epihastatoside (4) as well as verbascoside.

Iridoid glycoside biosynthesis in Penstemon secundiflorus. Another H-5, H-9 trans-iridoid glycoside.

Isolation and characterization of the new iridoid 10-hydroxy-(5 alpha H)-6-epidihydrocornin from Penstemon secundiflorus (Scrophulariaceae) is described. In biosynthetic experiments, deoxyloganic acid was incorporated into the trans-fused iridoid glycosides (5 alpha H)-6-epidihydrocornin and 10-hydroxy-(5 alpha H)-6-epidihydrocornin in P. secundiflorus. Formation of the trans-fused compounds is therefore a late event in the biosynthesis and does not occur during iridoid formation by cyclization of the open chain monoterpene precursor. In the same plant, 8-epideoxyloganic acid was not incorporated into the trans-iridoids. Deoxyloganic acid was also incorporated into 10-hydroxyhastatoside (which bears an 8 beta-methyl group), while 8-epideoxyloganic acid was incorporated into penstemoside (with an 8 alpha-methyl group). Thus, iridoid biosynthetic pathways leading from both deoxyloganic acid and 8-epideoxyloganic acid were found in the same plant.

The role of dynamic plantar pressures in diabetic foot ulcers.

OBJECTIVE: The significance of plantar pressure studies in detecting sites of plantar ulceration in diabetic patients was investigated. RESEARCH DESIGN AND METHODS: A total of 97 diabetic patients participated in this study. History and physical data, such as history of smoking, type of diabetes, ankle/brachial indexes, and the presence of protective sensory threshold, were collected. Using the EMED-SF plantar pressure analyzer, dynamic pressure variables, such as normalized peak pressure of maximum pressure picture (MPP), pressure-time integral (PTI), and force-time integral (FTI), were measured in each foot. Statistical analysis included descriptive statistics and analyses of variance. RESULTS: Out of 97 patients, 34 patients had no history of neuropathy and plantar ulceration (the diabetic control [DC] group). Another 14 patients had neuropathy with no previous history of plantar ulcers (the DN group), whereas the remainder of the patients had a history of peripheral neuropathy with plantar ulceration (the DU group). There were significant increases in MPP (P < 0.004) and PTI (P < 0.0004) levels in the DU group when compared with the DC group with the highest pressure present under the 4th and 5th metatarsal heads. No statistical significance existed among groups when comparing FTI levels. CONCLUSIONS: Neuropathic patients have an increase in dynamic plantar foot pressures placing them at risk for plantar ulceration. Instruments such as the EMED-SF system can be helpful in detecting possible sites of plantar ulcerations by locating the areas of maximum pressure.

Isolation of an angiotensin converting enzyme (ACE) inhibitor from Olea europaea and Olea lancea.

The aqueous extract of the leaves of Olea europaea and Olea lancea both inhibited Angiotensin Converting Enzyme (ACE) in vitro. A bioassay-directed fractionation resulted in the isolation of a strong ACE-inhibitor namely the secoiridoid 2-(3,4-dihydroxyphenyl)ethyl 4-formyl-3-(2-oxoethyl)-4 E-hexenoate (oleacein) (IC(50) = 26 µM). Five secoiridoid glycosides (oleuropein, ligstroside, excelcioside, oleoside 11-methyl ester, oleoside) isolated from Oleaceous plants showed no significant ACE-inhibition whereas, after enzymatic hydrolysis, the ACE-inhibition at 0.33 mg/ml was between 64% to 95%. Secoiridoids have not been described previously in the literature as inhibitors of ACE. Oleacein showed a low toxicity in the brine shrimp (Artemia satina) lethality test (LC(50) (24 h) = 969 ppm).

Three phenylethanoid glucosides of unusual structure from Chirita sinensis (Gesneriaceae).

From Chirita sinensis (Gesneriaceae) was isolated six phenylethanoid glucosides, namely the previously known positional isomers plantainoside A, calceolarioside A and calceolarioside B together with three new compounds named chiritoside A, B and C. It was proved by analysis of the NMR data that the chiritosides were the 4"-O-beta-glucopyranosyl-derivatives of the first three compounds.

Clinical experience with erythropoietin in continuous ambulatory peritoneal dialysis.

The purpose of this project was to determine a safe and effective Epogen (EPO) subcutaneous administration schedule for patients who were on continuous ambulatory peritoneal dialysis. To comply with the manufacturer's recommendation to enter a vial only once, a dosing regimen had to be established that used a standard dose of 2,000 or 4,000 units. The goal was to determine the frequency of administration that would achieve and maintain the target hematocrit. Twenty-six patients participated. The starting dose of 4,000 units was administered either two or three times per week. An average 8.3% point increase in hematocrit was seen in 8 weeks. When the target hematocrit of 33% to 35% was reached, the dose and or frequency of administration was decreased. Maintenance doses were established at 2,000 or 4,000 units weekly or biweekly. We were able to meet and maintain the target hematocrit by using 2,000 or 4,000 units per dose and adjusting the frequency.

Evaluation of dressing protocols that reduce peritoneal dialysis catheter exit site infections.

Exit site infections (ESIs) remain a major complication of peritoneal dialysis (PD). This study was designed to evaluate various catheter care techniques that would decrease ESIs during the 3 months following catheter implantation. Factors that affect wound healing were studied by evaluating preoperative and postoperative variables, skin cleansing agents, and three types of dressings. A 40% reduction in ESIs occurred following implementation of a new protocol that was developed from the knowledge acquired after studying the catheter care protocols.

Percutaneous dilation of ureteral strictures in renal transplant patients.

Percutaneous dilation of benign ureteral strictures was performed as an alternative to surgical therapy in 14 patients with renal transplants. Dilations were performed with balloon catheters in 13 patients and with a tapered angiographic catheter in one patient. Eleven strictures were successfully dilated (79%). There were three recurrences (21%). Follow-up in nine of the 11 successful cases ranged from 12 to 61 months (mean, 29 months; median, 24 months). There were no complications directly related to balloon dilation. The high success rate in this series may be related to the early diagnosis of strictures in these closely followed patients.

Percutaneous management of the urological complications of renal transplantation.

Percutaneous interventional procedures can be safely used to diagnose and treat the urological complications of renal transplantation. They can obviate surgery, or may allow conservative therapy until the condition of the patient is optimized for surgical intervention.

Urologic complications following renal transplantation: role of interventional radiologic procedures.

Seventy renal transplant recipients with suspected urologic problems underwent interventional radiologic procedures for further diagnosis and treatment. We found that 28 patients did not have urologic complications. The other 42 patients demonstrated a total of 62 complications, including 40 cases of obstruction, 12 cases of extravasation, and ten collections of pararenal fluid. Ultrasound and nuclear renal scans with both technetium-99m DTPA and iodine-131 hippuran were found to be sensitive screening techniques for the detection of these complications. Fifty of the 51 abnormalities were detected using a combination of these techniques. Percutaneous methods alone were successful in treating 15 urinary obstructions, eight pararenal fluid collections, and five urinary extravasations. We encountered six procedure-related complications, and there were three delayed infectious complications that were related to indwelling nephrostomy tubes. One of these three complications resulted in death. The results of our study suggest that invasive radiologic procedures can be safely used to diagnose and treat urologic complications in renal transplant recipients.

Percutaneous aspiration thromboembolectomy (PAT): an alternative to surgical balloon techniques for clot retrieval.

Percutaneous aspiration thromboembolectomy (PAT) is an angiographic technique that can be used to remove thromboembolic debris from the distal lower extremity circulation. This procedure employs a specially designed catheter-sheath system, which can be used alone or in combination with balloon angioplasty or thrombolytic drugs (streptokinase 10,000 U/hr or urokinase 100,000 U/hr for 6 hours) to remove thromboembolic material. PAT is best suited for treating iatrogenic emboli resulting from intra-arterial catheterization or balloon angioplasty but can be used as a supplement to Fogarty embolectomy when retained distal clot cannot be retrieved by surgical means and for removal of primary distal emboli of peripheral vascular or cardiac origin. PAT was used in 42 patients with acute threatening limb ischemia. Successful clot retrieval and limb salvage were achieved in 40 of the 42 patients (95%). The major complication was groin hematoma (7 of 42 patients, 17%) and one death occurred as a result of myocardial infarction (2.4%). PAT enhances the therapeutic role of angiography and can be used as an alternative to surgical embolectomy in selected patients.

Effect of lidocaine and bretylium on energy requirements for transthoracic defibrillation: experimental studies.

The purpose of this study was to determine the effect of the antiarrhythmic drugs lidocaine and bretylium on the minimal energy requirement for transthoracic defibrillation--the defibrillation threshold. Closed chest dogs were anesthetized with chloralose or pentobarbital; lidocaine was administered at varying rates for 2 hours and defibrillation threshold periodically redetermined. Similar protocols were followed for bretylium. Serum lidocaine levels from therapeutic to toxic ranges were obtained, and up to a 60% (p less than 0.05) increase in defibrillation threshold in the pentobarbital-anesthetized dogs was demonstrated. In chloralose-anesthetized dogs the lidocaine effect was modest, with only a 10 to 20% rise in defibrillation threshold (p = NS) despite similar increases in serum lidocaine levels. Thus, lidocaine increases the minimal energy requirements for transthoracic defibrillation, but this effect is in part anesthesia-related, indicating a lidocaine-pentobarbital interaction. When phentolamine was administered to chloralose-anesthetized dogs receiving lidocaine, defibrillation threshold rose 13% (p less than 0.05); this suggests that alpha-adrenergic receptor blockade is at least in part the mechanism of the pentobarbital-lidocaine interaction on defibrillation threshold. Bretylium with either anesthetic had no significant effect on defibrillation threshold.

Lymphatic disruption following abdominal aortic surgery.

Two cases of abdominal lymphatic disruption following surgery on the abdominal aorta are presented, one causing chylous ascites and the other resulting in a lymphocele. These complications have been only rarely described following abdominal vascular surgery. Both patients responded to percutaneous aspiration without recurrence. The radiologist has a major role in both the detection and management of this complication.

Percutaneous management of lymphatic fluid collections.

Eight lymphatic fluid collections were drained percutaneously. There were no immediate or late complications. Seven patients had follow-up; 1 required surgical drainage of a residual or recurrent lymphocele, and another had reaccumulated fluid in a lymphocele which was detected on autopsy. The remaining lymphatic collections responded to percutaneous drainage. Percutaneous drainage is safe and can be an effective tool in the management of lymphatic collections.