Familial adenomatous polyposis coli: five novel mutations in exon 15 of the adenomatous polyposis coli (APC) gene in Italian patients. Mutations in brief no. 225. Online

Germline mutations within the adenomatous polyposis coli (APC) gene, a tumor suppressor gene, are responsible for most cases of familial adenomatous polyposis (FAP), an autosomal dominantly inherited predisposition to colorectal cancer. To date, more than 300 germ-line causative mutations within this gene have been described (Beroud and Soussi, 1996). Of these, about 95% are chain-terminating mutations, and more than 60% have been localized within exon 15 (Nagase and Nakamura, 1993, Beroud and Soussi, 1996). Using polymerase chain reaction-single strand conformation polymorphism, protein truncation test (PTT) and DNA sequencing we have identified five new frameshift mutations (2523insCTTA, 2638delA, 2803insA, 3185delAA, 4145delTCATGT), all occurring within exon 15 and giving rise to truncated protein products. Two of these new mutations are of particular interest because of the unusual phenotypic features shown by probands. The phenotype of the proband bearing the 2523insCTTA mutation at codon 842 was very aggressive with onset of the symptoms at 12 years, while the patient bearing the 3185delAA mutation at codon 1062 exhibited features of an attenuated form of FAP (AAPC). Our data reiterate the great heterogeneity of the mutational spectrum in FAP that gives rise to an extreme variability of the clinical expression.     

Osteopetrosis: MR characteristics at 1.5 T

Four patients with proved osteopetrosis (three with the infantile malignant form and one with the benign form) were examined with magnetic resonance imaging at 1.5 T. All patients were studied in the coronal and sagittal planes using both short and long repetition time/echo time sequences. The infantile malignant form was characterized by a complete lack of signal from the marrow alternating with a signal intensity equivalent to that of the intervertebral disks, resulting in a "stepladder" appearance. In the benign form or after successful marrow transplantation in the infantile malignant form, intermediate or high signal intensity in the vertebrae was noted, suggesting the presence of some marrow elements.     

Direct versus indirect transfer for traumatic brain injury to James Cook University Hospital: a retrospective study

IntroductionPatients with traumatic brain injury are referred to the neurosurgical unit at James Cook University Hospital, Middlesbrough, either from local accident and emergency departments (direct transfer from the scene) or from other hospitals (indirect transfer). This study looked at the outcome in both groups.Material and methodsThis was a retrospective observational study using trauma audit research network data for patients treated for traumatic brain injury at the neurosurgery department at the neurosurgical unit at James Cook University Hospital.ResultsA total of 356 patients with traumatic brain injury were admitted under the care of neurosurgeons; 143 (40%) of these patients had a neurosurgical procedure. Of the patients undergoing a neurological procedure, 111 patients were transferred directly while 32 were indirect transfers; 213 patients were managed conservatively. Of those managed conservatively, 165 were transferred directly while 48 were indirect transfers.We compared the length of hospital stay and Glasgow Outcome Scale score for the patients based on whether they were conservatively managed or required surgery in the direct and indirect transfer groups. The difference in the length of stay in the surgical and conservative groups following direct and indirect transfer was insignificant (p = 0.07). The time to the operation in direct and indirect transfer was also not statistically significant (p = 0.06).ConclusionPatients are as safe, if not safer, by reaching the nearest trauma unit with facilities for resuscitation and imaging.     

Quality of life considerations in the treatment of hypertension

Only recently have practitioners recognized the potential effects of antihypertensive agents on quality of life. Unfortunately, few studies have been conducted to assess the effects of the newer antihypertensive agents. The introduction of four first-line antihypertensive agents permits further individualization in the selection of therapy, which will minimize adverse effects and increase the potential for prescribing a better tolerated drug regimen. Until large, well-controlled, randomized studies are conducted evaluating the effect of these antihypertensive agents on quality of life, practitioners must continue to rely on factors such as mechanism and duration of action, efficacy, side-effect profile, and cost to maximize antihypertensive efficacy and patient acceptance of therapy. A practitioner's heightened awareness for the side effects of antihypertensive agents, and the subtle quality-of-life changes that they may elicit will enable them to monitor more effectively and adjust therapy as necessary. This may increase the possibility of patients' compliance with their long-term treatment and ultimately improve patient outcome.     

A functional analytical technique for monitoring nutrient status and repletion. Part 3: clinical experience

This paper, third in a series describing a testing procedure for nutrient analysis, will focus on clinical experiences after targeted repletion of deficient nutrients. Part one described the Essential Metabolics Analysis (EMA) procedure (SpectraCell Laboratories, Houston, TX), which determines functional status of 19 nutrients by measuring lymphocyte growth responses to variations of a patented, chemically defined serum-free medium. Part two described validation studies of lymphocytes as markers for whole body nutrient status and metabolic functions. EMA provides a sensitive, specific, and accurate method of determining nutrient needs, requirements, or deficiencies for each individual.     

IMPACTED RIGHT UPPER CENTRAL INCISOR AND TRANSPOSITION OF TWO OTHER ANTERIOR TEETH ON THE SAME SIDE (A Case Report)

A young boy presented with an uncommon finding of impaction of upper right central incisor and transposition of canine and lateral incisor on the same side. Esthetic management of his cosmetic problem which included fixed appliance therapy followed by light cure restorations is discussed.KEY WORDS: Impaction, Transposition     

Preoperative chemoimmunotherapy with Carboplatin, epidoxorubicin, 5-Fluorouracil and alpha-2b interferon in locally advanced inoperable gastric-cancer

Twenty-six patients with locally advanced, inoperable gastric cancer were treated with carboplatin, epidoxorubicin, 5-fluorouracil (FEP) plus alpha 2b interferon. Total gastrectomy was performed in patients achieving clinical complete or partial response. The overall response rate after neoadjuvant chemotherapy was 67%. In 13/15 patients undergoing surgery no residual tumor was evident after resection. After a median follow-up of 14 months, 4/13 disease-free patients have relapsed. The median survival time is 13 months for all patients, and 19 months for disease-free patients; in four patients survival time exceeds twenty-four months. Our multimodality program is effective in locally advanced gastric cancer and warrants further evaluation.     

Neoadjuvant chemotherapy in locally advanced gastric-cancer - preliminary-results of a phase-ii trial with a modified famtx combination

Twenty-two patients with locally advanced inoperable gastric cancer received neoadjuvant chemotherapy with a modified 5-fluorouracil, doxorubicin, methotrexate (FAMTX) regimen. The patients who achieved at least a stable disease were considered eligible for surgery with curative intent, which was performed in 19 cases. 16 patients (all responsive to neoadjuvant chemotherapy) were rendered disease-free by the combined approach. No treatment-related deaths occurred; grade III leukopenia was observed in only 3 cases. The preliminary results of this study indicate the feasibility of our treatment approach; randomized trials are awaited to properly evaluate the role of neoadjuvant chemotherapy in locally advanced gastric cancer.     

Visual function correlates with nerve fiber layer thickness in eyes affected by ocular hypertension.

PURPOSE: To test whether the high variability observed when measuring pattern electroretinogram (PERG), visual evoked potentials (VEP), and spatial contrast sensitivity (SCS) in eyes with ocular hypertension is associated with variation in nerve fiber layer thickness, as measured by optical coherence tomography (OCT). METHODS: The study involved 32 untreated eyes (32 patients; age range, 29-64 years) showing a normal whiteon-white 24/2 Humphrey (San Leandro, CA) perimetry, IOP between 23 and 28 mm Hg, best corrected acuity of 20/20 or better, and none of the following papillary signs on conventional color stereo slides: rim notch(es), peripapillary splinter hemorrhages, or increased vertical-to-horizontal cup-to-disc ratio. On recruitment, each eye underwent SCS testing, OCT, PERG, and VEP recordings. Linear regression (Pearson's test) or Spearman's rank regression was adopted for the analysis of the data. RESULTS: The 95% confidence limits of the electrophysiological data were: PERG P50 latency, 59.3 to 63 msec; PERG P50 to N95 amplitude, 0.74 to 1.15 cmV; VEP P100 latency, 113 to 118 msec; VEP N75 to P100 amplitude, 3.81 to 4.90 micromV. The 360 degrees nerve fiber layer thickness overall (NFLO) ranged between 113 and 169 microm (145+/-16 microm; mean+/-SD) and significantly correlated with PERG P50 to N95 amplitude (r: 0.518; P = 0.002), PERG P50 latency (r: -0.470; P = 0.007), VEP N75 to P100 amplitude (r: 0.460; P = 0.008), VEP P100 latency (r = -0.422; P = 0.016) and SCS at 3 cyc/deg (r: -0.358; P = 0.044). CONCLUSIONS: The variability of PERG, VEP, and SCS testing observed in eyes with ocular hypertension is associated with differences in NFL thickness (the thinner the layer, the worse the visual function).