Suppression of hepatitis C virus by the flavonoid quercetin is mediated by inhibition of NS3 protease activity.

Phytochemicals exert antiviral activity and may play a potential therapeutic role in hepatitis C virus (HCV) infection. In this work, we aimed to isolate NS3 inhibitors from traditional Indian medicinal plants that were found, in our earlier study, to inhibit HCV NS3 protease activity and to evaluate their potential to inhibit HCV replication. A potent inhibitory effect of NS3 catalytic activity was obtained with Embelia ribes plant extracts. Quercetin, a ubiquitous plant flavonoid, was identified as the active substance in the fractioned extract. It was found to inhibit NS3 activity in a specific dose-dependent manner in an in vitro catalysis assay. Quercetin inhibited HCV RNA replication as analysed in the subgenomic HCV RNA replicon system. It also inhibited HCV infectious virus production in the HCV infectious cell culture system (HCVcc), as analysed by the focus-forming unit reduction assay and HCV RNA real-time PCR. The inhibitory effect of quercetin was also obtained when using a model system in which NS3 engineered substrates were introduced in NS3-expressing cells, providing evidence that inhibition in vivo could be directed to the NS3 and do not involve other HCV proteins. Our work demonstrates that quercetin has a direct inhibitory effect on the HCV NS3 protease. These results point to the potential of quercetin as a natural nontoxic anti-HCV agent reducing viral production by inhibiting both NS3 and heat shock proteins essential for HCV replication.

Laparoscopic management of acute small bowel obstruction.

BACKGROUND: As minimally invasive surgery gains ground, it is entering realms previously considered to be relative contraindications for laparoscopy. We reviewed our experience with the laparoscopic approach to the management of small bowel obstruction (SBO). METHODS: From December 1997 to November 2002, 65 patients underwent laparoscopic treatment for SBO. The operating surgeon attempted to identify a transitional point between distended and collapsed bowel and then address the obstruction at that point. RESULTS: Postoperative adhesions were the cause of the obstruction in 44 patients. Tumor was identified in five cases, hernia in four, bezoar in three, intussusception in three, acute appendicitis and pseudoobstruction in two cases each, and terminal ileitis in one case. The diagnostic accuracy of laparoscopy was 96.9%. Thirty-four patients (52%) were treated by laparoscopy alone. Thirteen patients (20%) required a small target incision for segmental resection. Eighteen operations were converted to formal laparotomy. The mean laparoscopy time was 40 min (range, 25-160). Patients resumed oral intake in 1-3 days. The complication rate was 6.4%. There were two deaths, but none related to laparoscopy. The mean hospital stay was 4.2 days. CONCLUSIONS: Laparoscopy is a useful minimally invasive technique for the management of acute SBO. It is an excellent diagnostic tool and, in most cases, a therapeutic surgical approach in patients with SBO. However, a significant number of patients will require conversion.

Antineurofilament antibodies in postpolio syndrome.

We determined the levels of antineurofilament antibodies in 29 patients with postpolio syndrome (PPS), 26 stable postpolio (PP) patients, 22 patients with ALS, and 20 normal controls (NCs). Patients with PPS had higher antibody levels to cholinergic neurofilaments than did all other groups. PP patients and those with ALS had antibody levels similar to those of NCs. The antibody binding level showed no relation to the age of the patients, duration of disease, or motor score.

CT and MR evaluation of the brain in patients with anorexia nervosa.

Thirteen adolescent girls with anorexia nervosa had MR imaging of the brain; 11 were also examined by CT. Fifteen children, ages 10-12 years, served as a control group. The CT and MR studies were evaluated qualitatively for cortical and central atrophic changes. CT detected sulcal and ventricular enlargement in 5/11 patients. On the MR images, enlarged sulci were seen in 10/13 and dilated ventricles in 5/13. In the anorectic patients, the range of the width of the third ventricle was 1-5 mm (mean, 3.2 mm) and the maximal distance between the anterior horns was 22.5-39.0 mm (mean, 30.0 mm). Anterior horns at their minimal width measured 11-30 mm (mean, 16.5 mm). The corresponding measurements in the control group were 1.5-3.5 mm (mean, 2.3 mm) for the third ventricle, 21-35 mm (mean, 28.5 mm) for the distance between the anterior horns, and 10-16 mm (mean, 12.8 mm) for their minimal width. Overall, the patient group had larger ventricles than the control group; however, the difference between the two groups was not significant. Measurement of the number of visible cortical sulci at one cut below the vertex yielded 2-11 sulci in the anorectic girls (mean, 6.6) versus 0-6 sulci (mean, 3.3) in the controls. These results are statistically significant (p = .0009), indicating peripheral volume loss in the anorectic patients. The MR examination did not reveal any additional structural or parenchymal changes when compared with the results of the CT studies. However, the pituitary glands of these patients did not have the expected normal pubertal hypertrophy on the MR examinations.(ABSTRACT TRUNCATED AT 250 WORDS)

Predictors of amputation for popliteal artery injuries.

BACKGROUND: Popliteal artery injuries continue to result in limb loss. This study identifies risk factors that predict amputation. METHODS: Over a 5-year period, a retrospective chart review was conducted of 80 consecutive patients with 81 popliteal artery injuries. RESULTS: The overall amputation rate was 16.5%. Blunt trauma carried a higher rate of amputation (47%) than penetrating injuries (6.2%); P < 0.0001). Associated fractures had a higher amputation rate, regardless of mechanism (odds ratio +2.7, 95% confidence limits 1.2 to 6.2). Fasciotomy at the time of operation was associated with reduced amputation rate. CONCLUSIONS: Blunt injuries and associated fractures carry an increased risk for amputation. Compartmental pressures should be appropriately monitored postoperatively. Fasciotomy at the time of vascular repair may be considered even without evidence of compartment syndrome.

Persistent and progressive parkinsonism after discontinuation of chronic neuroleptic therapy: an additional tardive syndrome?

Drug-induced parkinsonism is usually reversible, except in a small percentage of elderly patients. We describe two relatively young patients, who developed drug-induced parkinsonism during chronic treatment with neuroleptics for a psychotic disorder. Parkinsonism persisted, and markedly and progressively deteriorated after discontinuation of neuroleptic drugs. One patient had tremor as the most prominent sign and the other had mainly an akinetic-rigid syndrome. Neither had ever developed tardive dyskinesia. Both responded to levodopa therapy. Persistent drug-induced parkinsonism in our, and other reported on, elderly patients may be due to unmasking of preexisting subclinical idiopathic Parkinson's disease by neuroleptics. Theoretically, these drugs may precipitate degeneration of vulnerable, nigrostriatal neurons by generating cytotoxic free radicals or by attrition, due to accelerated neuronal firing rates.

Growth inhibition of laryngeal UM-SCC cell lines by tamoxifen. Comparison with effects on the MCF-7 breast cancer cell line.

Six laryngeal squamous cell carcinoma (SCC) cell lines and the MCF-7 breast cancer line, all of which contain estrogen and progesterone receptors, were tested for in vitro growth inhibition by the antiestrogen tamoxifen citrate. Cell line MCF-7 was more sensitive to growth retardation at 1 mumol/L of tamoxifen citrate, but SCC lines showed higher sensitivity than MCF-7 to cytotoxic effects at higher drug concentrations (7 to 10 mumol/L). A cytostatic level of growth inhibition was produced by 5 mumol/L tamoxifen citrate for both types of cell lines. When tamoxifen and estradiol were added to cultures simultaneously, partial reversal of growth inhibition was observed with MCF-7 but not with UM-SCC-5. All of the cell lines recovered from inhibition when tamoxifen was replaced with 0.1 mumol/L estradiol, but laryngeal SCC lines recovered equally well in estradiol-free medium, whereas MCF-7 recovered only partially in the absence of estradiol. These findings indicate that there are at least two tamoxifen receptor sites--one for which estradiol is a competitor and one for which it is not--and that tamoxifen reversibly blocks growth and may synchronize SCC cells.

The use of laparoscopy in abdominal emergencies.

BACKGROUND: The purpose of this article is to describe our experience using laparoscopy in the management of emergent and acute abdominal conditions. METHODS: Between March 1997 and November 2001, 277 consecutive minimally invasive procedures were performed for various nontrauma surgical emergencies. The indications for operation were nonspecific abdominal pain in 129 cases (46%), peritonitis in 64 cases (23%), small bowel obstruction in 52 cases (19%), complications after previous surgery or invasive procedures in 24 cases (9%), and sepsis of unknown origin in 8 cases (3%). RESULTS: Laparoscopy obtained a correct diagnosis in 98.6% of the cases. In 207 patients (75%), the procedure was completed laparoscopically. An additional 35 patients (12.5%) required a target incision. The remaining 35 patients (12.5%) underwent formal laparotomy. The morbidity rate was 5.8%. No laparoscopy-related mortality was observed. CONCLUSIONS: For patients with abdominal emergencies, the laparoscopic approach provides diagnostic accuracy and therapeutic options, avoids extensive preoperative studies, averts delays in operative intervention, and appears to reduce morbidity.

Continuous venovenous hemofiltration improves intensive care unit, but not hospital survival rate, in nonoliguric septic patients.

PURPOSE: The purpose of this study was to assess the effect of the early institution of continuous veno-venous hemofiltration on survival rates of nonoliguric, septic patients. MATERIALS AND METHODS: A retrospective study of 48 nonoliguric septic patients with PaO(2)/FIO(2) < or = 250, who were admitted to the General Intensive Care of the Soroka Medical Center. Twenty-six patients were treated with continuous venovenous hemofiltration (CVVH group) and 22 were treated by conventional therapy. The end point of treatment was weaning from mechanical ventilation, adequate oxygenation, and the need for minimal cardiocirculatory support. RESULTS: The study groups were similar in terms of age, gender, percentage of surgical or nonsurgical patients, APACHE II scores, and the Therapeutic Intervention Scoring System (TISS). Baseline serum urea and creatinine levels were similar in the groups, but the PAO(2)/FIO(2) ratio was significantly lower in the CVVH group (150.6 +/- 86 vs. 214.2 +/- 8.9). Twenty of the CVVH patients and 10 of the patients receiving conventional therapy were discharged from the intensive care unit (P =.03), but the hospital discharge rate was only slightly higher in the CVVH group (12 of 26) compared with the conventional therapy group (7 of 22) (P =.145). CONCLUSIONS: In this retrospective uncontrolled study, the mortality rate was considerably lower in nonoliguric septic patients who received continuous venovenous hemofiltration early in the course of the disease. The improved survival rate may be due to the ability of CVVH to eliminate mediators involved in the septic process, thus averting the multiple system organ failure consequent to septic insult.

Transient quadriceps paresis following local inguinal block for postoperative pain control.

Two patients were observed who had transient quadriceps paresis following local inguinal block for postoperative pain control following inguinal herniorrhaphy.

Odontogenic cysts related to pulpotomized deciduous molars: clinical features and treatment outcome.

OBJECTIVE: The purpose of this study was to assess the morbidity and outcomes associated with large cysts that developed in conjunction with pulpotomized deciduous molars. STUDY DESIGN: This retrospective study was based on the files of 18 patients who were referred to 2 oral surgery departments during a 10-year period (1986-1996). The inclusion criteria were large cyst lesions (>1 cm in diameter) and complete documentation. Data regarding symptoms at presentation, histologic and radiologic features, treatment modalities, morbidity, and outcomes were analyzed. RESULTS: An equal gender distribution of patients was found, as were a later development in males (12+/-2 years in boys, 9+/-2 years in girls) and a 5:1 ratio favoring the mandible over the maxilla. Treatment included enucleation (12 patients) and marsupialization (6 patients). The morbidity was high and included loss of permanent teeth (3 patients), extensive loss of alveolar bone (3 patients), use of flaps (2 patients), and adjuvant orthodontic treatment (9 patients). CONCLUSION: Failure of early detection and treatment of cysts that develop in conjunction with pulpotomized deciduous molars can cause considerable morbidity. Therefore, periodic clinical and radiologic follow-up until the eruption of succedaneous teeth is recommended.

Acute mastoiditis--the antibiotic era: a multicenter study.

OBJECTIVES: To evaluate the clinical course and identify the causative organisms of acute mastoiditis in a community where most of the patients who develop acute otitis media are treated with antibiotics. METHODS: A multicenter retrospective review of a series of 223 consecutive cases of acute mastoiditis. SETTING: Nine secondary or tertiary academic or non-academic referral centers. RESULTS: Prior to the diagnosis of acute mastoiditis, 121 of the patients (54.3%) had been receiving oral antibiotic treatment for acute otitis media for periods ranging from 1 to 21 days (mean 5.3 days). Samples for bacterial culture were obtained from 152 patients. Cultures were negative in 60 patients. The organisms isolated in the 92 positive cultures were: Streptococcus pneumoniae (15 patients), Streptococcus pyogenes (14 patients), Staphylococcus aureus (13 patients), Staphylococcus coagulase negative (three patients), Pseudomonas aeruginosa (eight patients), Haemophilus influenzae (four patients), Proteus mirabilis (two patients), Escherichia coli (two patients), Klebsiella pneumoniae (one patient), Enterobacter (one patient), Acinetobacter (one patient), anaerobic gram-negative bacilli (one patient), and fungi (two patients). Ten patients had mixed flora. Sixteen patients presented with complications (cerebellar abscess, perisinus empyema, subdural abscess or empyema, extradural abscess, cavernous sinus thrombosis, lateral sinus thrombosis, bacterial meningitis, labyrinthitis, petrositis, or facial nerve palsy). CONCLUSIONS: Antibiotic treatment cannot be considered an absolute safeguard against the development of acute mastoiditis. Early myringotomy for acute otitis media seems to decrease the incidence of complications. The distribution of causative organisms in acute mastoiditis differs from that in acute otitis media. Intracranial complications in acute mastoiditis are not rare. Because of the diversity of causative organisms in acute mastoiditis and the growing resistance of bacteria to the various antibiotics, all means to obtain a sample for culture prior to antibiotic treatment, including general anesthesia.

Laparoscopically guided distal ventriculoperitoneal shunt placement.

In standard techniques for performing ventriculoperitoneal shunts, the peritoneal catheter is threaded more or less blindly into the peritoneal cavity. Using laparoscopic techniques allows accurate peritoneal placement, without a large incision, even in replacement procedures and in patients with previous abdominal operations. We performed 28 laparoscopically guided ventriculoperitoneal shunt placements and shunt revisions in 24 patients with hydrocephalus (aged 6-80 years). Sixteen of 24 patients (67%) had previous abdominal surgery. Laparoscopic shunt placement was successful in all patients. Mean operative time was 63 +/- 34.9 minutes (range 15-150 minutes). In 2 patients, broken and disconnected distal parts of previously inserted shunts were removed from the abdomen. One shunt was removed following infection and other one was revised due to shunt malfunction. Three patients required revision of the cranial part of the shunt. Laparoscopically guided distal ventriculoperitoneal shunt placement provides definite patient benefits: it allows shunt placement under direct vision, associated with reduced trauma to the abdominal wall, and avoids a consequent risk of intra-abdominal adhesions.

[Thyroglossal duct cyst].

Thyroglossal duct cysts are embryologic anomalies arising from epithelial remnants of the duct left after the descent of the developing thyroid. Clinical, operative and pathological findings in 124 patients operated on in the past 14 years were analyzed. There were 60 males and 64 females. 69 (56%) were under 10 years of age and the youngest was 6 months old. 26 (21%) were over the age of 30, and the oldest was 72 years old. All excisions were performed in accordance with the Sistrunk procedure, which includes removal of the body of the hyoid bone. Overall recurrence was 6.4%, but in infected cysts or cysts with a fistula to the skin, it was 3.5 times greater. In 20% the cyst was located off the midline. The lining of the cysts was cuboidal, columnar, pseudostratified or stratified squamous epithelium, and varied according to the location of the cyst. There were no malignant changes.

[Extracorporeal shock wave lithotripsy for cystine urolithiasis].

We present 31 patients with cystine urolithiasis referred to our extracorporeal shock wave lithotripsy (ESWL) center since 1985. This group differed statistically from the other 3000 patients treated by us for urolithiasis with regard to age, stone burden, number of previous operations, and known duration of urolithiasis. The average known duration in those with cystine stones was 15 years. Of 26 patients with such a history, 22 had an average of 2 operations each. At referral, 14 had bilateral stones and among the others there were 5 nonfunctioning kidneys. Of 26 referred with a diagnosis of cystine nephrolithiasis, only 11 were being treated medically. At presentation, 31 had no stones and 1 was being treated medically. In the other 29 patients, 44 renal-ureteral units had urolithiasis. During follow-up 2 ureteral stones were discharged spontaneously and the other units were treated by ESWL, surgery and/or ureteroscopy, and percutaneous irrigation. 36/42 units were free of significant stone residue, but in 4 there were large gravel remains; 1 kidney was removed primarily and 1 kidney lost its function following prolonged obstruction after ESWL. During follow-up, of 11 patients unable to tolerate D-penicillamine and treated by urinary alkalinization alone, 3 have already formed new stones.

[Rational use of albumin].

The use of albumin has been a matter of debate since its introduction in the 1940's. Albumin is not only expensive but may also be harmful when administered inappropriately. Until recently our use of albumin was controlled by a number of authorized physicians who signed all albumin prescriptions. In August 1998, a multidisciplinary team reviewed the indications for albumin use and introduced simple guidelines for its supply and administration. As a result, the use of albumin has decreased by almost 70%. This indicates that rational use of albumin can be achieved by appropriate guidelines, without requiring administrative limitations. We believe that this conclusion holds true for other diagnostic and therapeutic procedures as well.