Cryptococcus neoformans Chemotyping by Quantitative Analysis of 1H Nuclear Magnetic Resonance Spectra of Glucuronoxylomannans with a Computer-Simulated Artificial Neural Network

The complete assignment of the proton chemical shifts obtained by nuclear magnetic resonance (NMR) spectroscopy of de-O-acetylated glucuronoxylomannans (GXMs) from Cryptococcus neoformans permitted the high-resolution determination of the total structure of any GXM. Six structural motifs based on an α-(1→3)-mannotriose substituted with variable quantities of 2-O-β- and 4-O-β-xylopyranosyl and 2-O-β-glucopyranosyluronic acid were identified. The chemical shifts of only the anomeric protons of the mannosyl residues served as structure reporter groups (SRG) for the identification and quantitation of the six triads present in any GXM. The assigned protons for the mannosyl residues resonated at clearly distinguishable positions in the spectrum and supplied all the information essential for the assignment of the complete GXM structure. This technique for assigning structure is referred to as the SRG concept. The SRG concept was used to analyze the distribution of the six mannosyl triads of GXMs obtained from 106 isolates of C. neoformans. The six mannosyl triads occurred singularly or in combination with one or more of the other triads. The identification and quantitation of the SRG were simplified by using a computer-simulated artificial neural network (ANN) to automatically analyze the SRG region of the one-dimensional proton NMR spectra. The occurrence and relative distribution of the six mannosyl triads were used to chemotype C. neoformans on the basis of subtle variations in GXM structure determined by analysis of the SRG region of the proton NMR spectrum by the ANN. The data for the distribution of the six SRGs from GXMs of 106 isolates of C. neoformans yielded eight chemotypes, Chem1 through Chem8.     

Rat liver adenyl cyclase activity in various thyroid states

Thyroidectomized and euthyroid rats were injected with three doses of triiodothyronine (T(3)) or of the diluent over a 6 day period, and liver homogenates were assayed for basal, epinephrine-stimulated, and NaF-stimulated adenyl cyclase activity. Based on NaF-stimulated levels, total adenyl cyclase activity, expressed per milligram of liver protein, was increased after thyroidectomy. Administration of T(3) to either hypothyroid or euthyroid rats, however, had no effect on the NaF-stimulated levels. Basal and epinephrine-stimulated enzyme activities were the same in hypothyroid, euthyroid, and hyperthyroid (euthyroid + T(3)) liver homogenates. In contrast, injections of T(3) in hypothyroid rats increased the activities of basal and epinephrine-stimulated adenyl cyclase. In view of the findings in euthyroid and hyperthyroid liver, it is possible that this effect is transient. In general, no correlation was found between the effects of thyroid hormone on respiration and on adenyl cyclase activity of the rat liver. These results imply that the hepatic thermogenic response to thyroid hormone is not mediated by stimulation of adenyl cyclase activity with the possible exception of the early effects of T(3) in the athyroid rat.     

Outcome of laparoscopic Nissen fundoplication in patients with body mass index ≥35

Background To date, few studies have examined the effect of morbid obesity on the outcome of laparoscopic antireflux surgery and results have been conflicting. The aim of this work was to study the outcome of laparoscopic Nissen fundoplication (LNF) in patients with body mass index (BMI) ≥ 35. Methods We prospectively followed 70 patients (15 men, 55 women) with a proven diagnosis of gastroesophageal reflux disease (GERD) and a mean BMI of 38.4 ± 0.5 (range, 35–51) who underwent LNF. All patients underwent 24-h pH study, esophageal manometry, upper gastrointestinal (GI) endoscopy, and GERD symptom score before and 6 months after LNF. Surgical outcomes were compared to those of 70 sequential nonobese patients (BMI < 30) who also underwent LNF. Results LNF was completed laparoscopically in 69 of 70 patients in the morbidly obese (MO) group and in all 70 patients in the normal-weight (NW) group. The mean operative time for the MO group was not significantly longer than that for the NW group (55.9 ± 2.3 min vs 50.0 ± 2.1 min), but the mean length of stay was significantly longer (3.17 ± 0.2 days vs 2.2 ± 0.1 days, p < 0.0001) in the MO group. There was one postoperative complication (a transhiatal herniation of the stomach) in the morbidly obese group. In both patient groups, LNF resulted in a significant increase in lower esophageal sphincter (LES) pressures. This was associated with a significant decrease in percent acid reflux in 24-h testing and a significant improvement in GERD symptom score in both groups, although patients in the MO group had a significantly higher mean reflux symptom score after surgery than did those in the NW group. After a mean follow-up of 41.6 ± 2.9 months, one patient in the MO group required reoperation and one proton pump inhibitor therapy (PRN PPI), as required. Conclusions Morbid obesity does not adversely affect the outcome of LNF. The conversion rate is low when performed by an experienced surgeon. Presented at the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) meeting, Los Angeles, CA, USA, 12–15 March 2003     

Long-term outcomes of laparoscopic surgery for colorectal cancer

Multiple reports have outlined the potential benefits of the laparoscopic approach to colon surgery. Recently, randomized control trials have demonstrated the safety of applying these techniques to colorectal cancer. This study examined the long-term follow-up assessment of patients after laparoscopic colorectal cancer resections and compared them with a large prospective database of open resections. A total of 231 resections were performed for adenocarcinoma of the colon or rectum between 1992 and 2004. Of these 231 resections, 93 were rectal (40.3%) and 138 were colonic (59.7%). A total of 8 (3.2%) of the resections were performed as emergencies, and 27 (11.7%) were converted to open surgery. The mean follow-up period was 35.84 months (range, 0-132 months). The disease recurred in 51 of the patients (22.1%) before death, involving 14 (6.1%) local and 37 (16%) distant recurrences. Only two patients had wound recurrences (0.8%), and both patients had widespread peritoneal recurrence at the time of diagnosis. The overall survival rate was 65.3% at 60 months and 60.3% at 120 months. The disease-free survival rate was 58% at 60 months and 56% at 120 months. Laparoscopic techniques can be applied to a wide range of colorectal malignancies without sacrificing oncologic results during a long-term follow-up period.     

Esophageal and lower esophageal sphincter pressure profiles 6 and 24 months after laparoscopic fundoplication and their association with postoperative dysphagia

Background: It has been suggested that antireflux surgery may cause an improvement in esophageal motor function (EMF) and lead to reduced postoperative dysphagia. Methods: We evaluated the changes in dysphagia symptom scores and esophageal and lower esophageal sphincter (LES) pressures in patients before (n= 381), at 6 months (n= 260), and at 24 months (n= 97) after laparoscopic fundoplication. Results: There was a significant increase in LES basal and nadir pressure following surgery in all patients and an improvement in EMF only in patients with poor preoperative esophageal motor function. A total of 76% of the patients reported no dysphagia or an improved dysphagia score 6 and 24 months after surgery. This improvement was more marked in patients with poor EMF. An improvement in EMF did not correlate with the improvement in dysphagia score reported by other patients. Patients with increased dysphagia scores 2 years after surgery had significantly higher LES basal and nadir pressures as compared to other patients. Conclusions: Laparoscopic Nissen fundoplication is associated with an overall reduction in dysphagia scores and leads to an improvement in esophageal motor function in patients with poor preoperative esophageal motility. Tightness and inadequate relaxation of the wrap during swallowing may be a determinant of long-term dysphagia. Received: 5 May 1997/Accepted: 19 August 1997     

A Comparison of Buccal Midazolam and Intravenous Diazepam for the Acute Treatment of Seizures in Children

Objective

The purpose of the present study is to compare efficacy and safety of buccal midazolam with intravenous diazepam in control of seizures in Iranian children.

Methods

This is a randomized clinical trial. 92 patients with acute seizures, ranging from 6 months to 14 years were randomly assigned to receive either buccal midazolam (32 cases) or intravenous diazepam (60 cases) at the emergency department of a children''s hospital. The primary outcome of this study was cessation of visible seizure activity within 5 minutes from administration of the first dosage. The second dosage was used in case the seizure remained uncontrolled 5 minutes after the first one.

Findings

In the midazolam group, 22 (68.8%) patients were relieved from seizures in 10 minutes. Meanwhile, diazepam controlled the episodes of 42 (70%) patients within 10 minutes. The difference was, however, not statistically significant (P=0.9). The mean time required to control the convulsive episodes after administration of medications was not statistically significant (P=0.09). No significant side effects were observed in either group. Nevertheless, the risk of respiratory failure in intravenous diazepam is greater than in buccal midazolam.

Conclusion

Buccal midazolam is as effective as and safer than intravenous diazepam in control of seizures.     

Prevalence of ATP7B Gene Mutations in Iranian Patients With Wilson Disease

Background

Wilson disease (WD) is an autosomal recessive disorder. The WD gene, ATP7B, encodes a copper-transporting ATPase involved in the transport of copper into the plasma protein ceruloplasmin and in excretion of copper from the liver. ATP7B mutations cause copper to accumulate in the liver and brain.

Objectives

We examined the ATP7B mutation spectrum in Wilson disease patients in Iran.

Patients and Methods

Genomic DNA was extracted from patients with Wilson disease. The entire coding region of the ATP7B gene was amplified using PCR and analyzed using direct sequencing.

Results

We identified five novel mutations in 5 Iranian patients with Wilson disease. The first was a transversion, c.2363C > T, which led to an amino acid change from threonine to isoleucine. The second mutation was a deletion, c.2532delA (Val845Ser), which occurred in exon 10. The third mutation was a transition mutation, c.2311C > G (Leu770Leu), which occurred in the TM4 domain of the ATP7B protein. The fourth mutation was a transversion, (c.3061G > A) (Lys1020Lys), in exon 14. Lastly, we identified a transversion, c.3206C > A (His1069Asn) in exon 14 which led to a change in function of the ATP loop domain of the ATP7B protein. The H1069Q mutation was identified as the most common mutation in our study population.

Conclusions

Based on our findings, the H1069Q may be a biomarker that can be used in a rapid detection assay for diagnosing WD patients