Ile to Val polymorphism at codon 655 of HER-2 gene and breast cancer risk in Iranian women

The earlier reports on the association between the Ile to Val polymorphism at codon 655 of HER-2 and susceptibility to breast cancer has not been found to hold true for all ethnic populations. Two hundred and four cases and 138 controls were collected to investigate the association of HER-2 Ile655Val polymorphism with the risk of breast cancer development and progression in Iranian population. This association was not found to be significant in the present study (OR = 1.16, 95% CI: 0.67-2.03). The association between HER-2 genotypes frequency and clinicopathological data was also insignificant, suggesting that the HER-2 polymorphism at codon 655 is unlikely to be a susceptibility locus in Iranian patients with breast cancer.     

Hysteroscopic endometrial ablation is an effective alternative to hysterectomy in women with menorrhagia and large uteri

STUDY OBJECTIVES: To examine the feasibility, safety, and outcome of hysteroscopic endometrial ablation, and to determine the volume of fluid absorbed during resection versus rollerball coagulation in women with menorrhagia and large uteri. DESIGN: Retrospective review (Canadian Task Force classification II-2). SETTING: University-affiliated teaching hospital. PATIENTS: Forty-two consecutive patients (mean +/- SD age 45.6 +/- 6 yrs) with uterine size greater than 12 weeks (cavity >12 cm). Intervention. Endometrial ablation; 26 (62%) women were pretreated to thin the endometrium. MEASUREMENTS AND MAIN RESULTS: Resection was performed in 27 patients (65%) and rollerball coagulation in 15 (35%). Ablation was successfully performed in all patients in a day surgery setting. Multiple regression analysis examined the relationship of uterine size, pretreatment, procedure, and duration of surgery to amount of glycine absorbed. Glycine absorption was higher with resection than with coagulation (p = 0.04). Fluid absorption correlated with type of procedure (r = 0.32, p = 0.04) but not with duration of the procedure, uterine size, or pretreatment. One patient with uterine fibroids and one with endometrial adenocarcinoma had hysterectomy. With follow-up of 39 (95%) of 41 women (excluding the one with adenocarcinoma) for 14 +/- 2 months, 38 (93%) were very satisfied. Thirty (73%) had amenorrhea, six (15%) had hypomenorrhea (<3 pads/day), and three (7%) had eumenorrhea (<10 pads/day). CONCLUSION: Hysteroscopic endometrial ablation may be a feasible, safe, and effective alternative to hysterectomy in women with menorrhagia and large uteri.     

Microvascular decompression surgery in the United States, 1996 to 2000: mortality rates,morbidity rates,and the effects of hospital and surgeon volumes

OBJECTIVE: Microvascular decompression (MVD) is associated with low mortality and morbidity rates at specialized centers, but many MVD procedures are performed outside such centers. We studied short-term end points after MVD in a national hospital discharge database sample. METHODS: A retrospective cohort study was performed by using the Nationwide Inpatient Sample, 1996 to 2000. RESULTS: The sample included 1326 MVD procedures for treatment of trigeminal neuralgia, 237 for treatment of hemifacial spasm, and 27 for treatment of glossopharyngeal neuralgia, performed at 305 hospitals by 277 identified surgeons. The mortality rate was 0.3%, and the rate of discharge other than to home was 3.8%. Neurological complications were coded in 1.7% of cases, hematomas in 0.5%, and facial palsies in 0.6%, with 0.4% of patients requiring ventriculostomies and 0.7% postoperative ventilation. Trigeminal nerve section was also coded for 3.4% of patients with trigeminal neuralgia, more commonly among older patients (P = 0.08), among female patients (P = 0.03), and at teaching hospitals (P = 0.02). The median annual caseloads were 5 cases per hospital (range, 1-195 cases) and 3 cases per surgeon (range, 1-107 cases). With adjustment for age, sex, race, primary insurance, diagnosis (trigeminal neuralgia versus hemifacial spasm versus glossopharyngeal neuralgia), geographic region, admission type and source, and medical comorbidities, outcomes at discharge were superior at higher-volume hospitals (P = 0.006) and with higher-volume surgeons (P = 0.02). Complications were less frequent after surgery performed at high-volume hospitals (P = 0.04) or by high-volume surgeons (P = 0.01). The rate of discharge other than to home was 5.1% for the lowest-volume-quartile hospitals, compared with 1.6% for the highest-volume-quartile hospitals. Volume and mortality rate were not significantly related, but three of the four deaths in the series followed procedures performed by surgeons who had performed only one MVD procedure that year. Length of stay (median, 3 d) and hospital volume were not significantly related. Hospital charges were slightly higher at higher-volume hospitals (P = 0.007). CONCLUSION: Although most MVD procedures in the United States are performed at low-volume centers, mortality rates remain low. Morbidity rates are significantly lower at high-volume hospitals and with high-volume surgeons.     

Design, synthesis, and calcium channel antagonist activity of new 1,4-dihydropyridines containing 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent

A series of dialkyl, dicycloalkyl, and diaryl ester analogues of nifedipine, in which the ortho-nitro phenyl group at position 4 is replaced by the 4-(5)-chloro-2-ethyl-5-(4)-imidazolyl substituent, were synthesized and evaluated as calcium channel antagonists using the high K+ contraction of guinea pig ileal longitudinal smooth muscle. The results for the symmetrical ester series showed that increasing the length of the chain in C3- and C5-ester substituents increased the activity and the most active compound was the diphenylethyl ester derivative, so it was more active than the reference drug nifedipine. In unsymmetrical diester series, when R1 is methyl or ethyl, increasing lipophilic properties in the R substituent, increased the activity. The most active compounds were methyl/phenethyl and ethyl/phenethyl ester derivatives, being slightly more active than nifedipine.     

Effect of excipients on the stability and aerosol performance of nebulized aviscumine.

Pulmonary delivery is an attractive alternative route to deliver protein drugs that are currently delivered by injection. Inhalation therapy via nebulizers is a well accepted way for pulmonary application of proteins considering the formulation difficulties of MDIs or DPIs. This research presents the effect of variable excipients on the stability and aerosol performance of freeze-dried aviscumine after reconstitution and nebulization. Aviscumine formulations containing 100 mmol/L Tris buffer, 0.1% (w/v) Polysorbate 80, 0.01% (w/v) Na(2)-EDTA and 8% (w/v) Hydroxyethyl starch have been lyophilized and reconstituted with a buffered isotonic solution pH 8. The aviscumine activity was determined by a binding assay directly after reconstitution and after nebulization with a PariBoy air-jet nebulizer, a Multisonic and a Systam ultrasonic nebulizer. The stabilization of aviscumine by the addition of variable buffer salts to the reconstitution medium, such as 50, 100, and 200 mmol/L Tris buffer, 20 and 100 mmol/L phosphate buffer, and 20 and 100 mmol/L Tricine buffer, was studied. About 50% of aviscumine activity was lost after 20 min nebulization time without any additives. Nevertheless, higher buffer concentrations confer greater stability. About 70% of the aviscumine activity could be retained by the addition 0.03% octanoyl-N-methylglucamide and 100 mmol/L Tricine to the reconstitution medium.     

Prevalence of celiac disease in Iranian children with idiopathic short stature

AIM： To determine the prevalence of celiac disease （CD） in children with idiopathic short stature （ISS） and the diagnostic value of immunoglobulin （Ig） A G antigliadin antibodies （AGA） and transglutaminase （TTG） antibodies for CD.METHODS： A total of 104 children （49 male, 55 female） with ISS without a specific etiology were studied. Extensive endocrine investigations had shown no abnormalities in any subject. Anthropometric parameters and IgA AGA and IgA TTG antibodies were evaluated in this study group. These antibodies were measured by enzyme-linked immunosorbent assay. All patients were referred for an endoscopic intestinal biopsy. The biopsy samples were classified according to revised Marsh criteria （UEGW 2001）.RESULTS： We detected positive IgA TTG antibodies in 36 and IgA AGA in 35 of these patients. Thirty one IgA TTG antibody positive and 28 IgA AGA positive subjects showed histological abnormalities compatible with celiac disease （33.6%）. Sensitivity, specificity, positive predictive value （PPV） and negative predictive value for IgA AGA were found to be 80%, 88.4%, 77.8% and 89.7%, respectively. Sensitivity, specificity and PPV for IgA TTG antibodies were 88.6%, 94.2% and 88.6%, espectively.CONCLUSION： We conclude that the prevalence of celiac disease is high in patients with ISS and it is important to test all children with ISS for celiac disease by measuring serologic markers and performing an intestinal biopsy.     

Spinal epidural abscess: clinical presentation, management, and outcome

BACKGROUND: We sought to describe the clinical characteristics of patients with spinal epidural abscess and to relate presentation and treatment to short-term clinical and neurologic outcome. METHODS: We retrospectively reviewed the records and radiographic images of all patients admitted to our institution with a diagnosis of spinal epidural abscess between January 1995 and March 2001. RESULTS: Thirty males and 18 females were admitted with spinal epidural abscess. Median age was 61 years (range, 31-84). Twenty-three of 48 patients were febrile at presentation and the mean white blood cell (WBC) count was 15.5 (range, 4.0-38.7). Twenty-seven patients presented with motor deficits, 17 with pain alone, 2 with sepsis, 1 with dysphagia, and 1 incidentally on spinal imaging. Intravenous drug abuse was the most common risk factor (13 patients) followed by the presence of nonspinal infection, including endocarditis (10 patients). Blood cultures were positive in 29 patients. Staphylococcus aureus was the most common organism cultured from abscesses. Collections were located in the cervical spine in 11 patients, cervicothoracic in 4, thoracic in 7, thoracolumbar in 4, and lumbosacral in 22. One patient harbored both cervical and lumbar epidural abscesses. Twenty-three patients initially received nonoperative therapy with antibiotics alone; 25 underwent urgent surgery. Eleven patients initially treated with antibiotics eventually deteriorated and required delayed surgery. Patients receiving antibiotics suffered a significantly greater number of unfavorable outcomes (clinical deterioration or death) than those in the early surgical group (P < 0.005). CONCLUSIONS: Patients with spinal epidural abscess may be normothermic and have normal WBC counts. Urgent surgery was more likely to be offered to patients presenting with neurologic deficits than with pain alone. Patients treated without early surgery were significantly more likely to deteriorate and suffer poor outcomes.