Inguinal hernia: Challenging the traditional indication for surgery in asymptomatic patients

Background: It is generally accepted that most inguinal hernias should be operated on electively in order to avoid the high morbidity and mortality associated with incarceration and small bowel obstruction. The present study reassesses the indication for surgery in asymptomatic inguinal hernia patients. Methods: We analyzed profiles, separately, for elective and emergency inguinal herniorrhaphies and compared the morbidity and mortality rates. Results: Two hundred randomly selected elective hernia repairs were compared with 67 incarcerated cases. Postoperative complications were more common following emergency (23.9%) than elective repair (10.5%); however, in both groups, minor complications predominated. The mortality rate in the incarcerated group (6%) was clearly linked with a high preoperative American Society of Anesthesiologists (ASA) score. A bowel resection rate of 4.5% was found in the incarcerated cases, which was not correlated with mortality. Conclusions: Patients with asymptomatic inguinal hernia and unfavorable medical conditions should be recommended an elective repair, preferably under local anesthesia, to avoid the high mortality associated with an emergency operation.     

A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls

BACKGROUND: Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients. METHODS: The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease. RESULTS: Thirty-five patients with breast carcinoma had one or more single-base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P=0.006; Fisher two-sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P=0.024; Fisher two-sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients. CONCLUSIONS: Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma.     

A functional polymorphism in the EGF gene is found with increased frequency in glioblastoma multiforme patients and is associated with more aggressive disease

Glioblastoma multiforme, the most aggressive form of primary brain tumor in adults, is nearly universally fatal, with 5-year survivals of <5% (P. Kleihues and W. K. Cavenee, eds., pp. 1-314, Lyon: IARC, 2000). Alterations in the epidermal growth factor receptor (EGFR) are common events in many glioblastoma. We hypothesized that a polymorphism in the 5'-untranslated region of the epidermal growth factor (EGF) gene, a natural ligand of the EGFR, may play a role in the genesis of these malignant gliomas. We find that patients with the GA or GG genotype have higher tumoral levels of EGF, irrespective of EGFR status, that they are more likely to recur after surgery, and that they have a statistically significant shorter overall progression-free survival than patients with the AA genotype. These findings suggest that a single nucleotide polymorphism in EGF may play a role in the formation of glioblastomas, is a useful and powerful prognostic marker for these patients, and may be a target for tumor therapy.     

Theta reset produces optimal conditions for long-term potentiation

Connections among theta rhythm, long-term potentiation (LTP) and memory in hippocampus are suggested by previous research, but definitive links are yet to be established. We investigated the hypothesis that resetting of local hippocampal theta to relevant stimuli in a working memory task produces optimal conditions for induction of LTP. The timings of the peak and trough of the first wave of reset theta were determined in initial sessions and used to time stimulation (4 pulses, 200 Hz) during subsequent performance. Stimulation on the peak of stimulus-reset theta produced LTP while stimulation on the trough did not. These results suggest that a memory-relevant stimulus produces a phase shift of ongoing theta rhythm that induces optimal conditions for the stimulus to undergo potentiation.     

A follow up study of patients with paraneoplastic neurological disease in the United Kingdom

OBJECTIVES: To examine the range of clinical phenotypes, tumour associations, relevant investigations, response to therapy and outcome in a large series of non-selected patients with paraneoplastic neurological disease (PND) affecting the central nervous system (CNS) in the United Kingdom. METHODS: Data were obtained on patients either through direct referral or through the British Neurological Surveillance Unit (BNSU) from February 2000 to January 2001. Physicians were asked to supply information about age and sex of patients, presenting neurological syndromes, the basis of the diagnosis of PND, any associated malignancy, and treatment. Case notes were reviewed and follow up data obtained where possible one year after notification. RESULTS: A total of 63 patients (48 females, 15 males) were identified, 48 through the BNSU and 15 through direct referral. Of these 52 were diagnosed as having definite PND, 10 probable PND, and 1 possible PND. The median age of onset of PND was 66 years (range 30-80 years) and only 7 patients (11%) were less than 50 years at presentation. In 53 patients (84%) the PND preceded the diagnosis of cancer. Paraneoplastic sensory neuronopathy, paraneoplastic encephalomyelitis, and paraneoplastic cerebellar degeneration (PCD) were the most common syndromes reported. The benefit of magnetic resonance imaging in the diagnosis of the disease was limited, while fluorodeoxyglucose positron emission tomography was shown to be useful for the detection of an occult malignancy in 10 out of 14 patients. Antineuronal antibodies were positive in 44/57 (77%) of cases. The following tumours were diagnosed: small cell lung cancer (30%), breast cancer (14%), ovarian cancer (8%), non-small cell lung cancer (8%), Hodgkin's lymphoma (6%), other (16%). With the exception of PCD associated with mesothelioma all other tumours diagnosed in these patients had been previously documented as being associated with PND. Only treatment of the tumour was found to be associated with a stable or improved neurological outcome at last follow up (Fisher's exact test = 4.7, p<0.03). Median survival time was 43 months (95% CI 28 to 57) from onset of neurological disease as calculated using the Kaplan-Meier survival analysis. CONCLUSIONS: PND has a striking female preponderance usually affecting patients in their sixth decade and above. The median survival in our study was 43 months. The majority of patients with PND are not known to have cancer at the time of diagnosis. Our study confirms the importance of diagnosing and treating the underlying tumour.     

Treatment of thyroid associated ophthalmopathy with periocular injections of triamcinolone

AIM: To evaluate the efficacy of periocular triamcinolone acetonide for the treatment of thyroid associated ophthalmopathy (TAO), and the presence of ocular or systemic adverse effects. METHODS: A multicentre prospective pilot study was performed on patients diagnosed with Graves' ophthalmopathy less than 6 months before entry to the study. Patients were admitted to the study and were randomised into two groups: treatment and control. The treatment group received four doses of 20 mg of triamcinolone acetate 40 mg/ml in a peribulbar injection to the inferolateral orbital quadrant. Both groups were evaluated by measuring the area of binocular vision without diplopia on a Goldmann perimeter and the size of the extraocular muscles on computed tomography (CT) scans. Ophthalmological and systemic examinations were done to rule out ocular and systemic adverse effects. Follow up was 6 months for both groups. RESULTS: 50 patients were eligible for the study. 41 patients completed the study. There was an increase in the area of binocular vision without diplopia in the treatment group (Sigma initial: mean 231.1 (SD 99.9) and final absolute change, mean 107.1 (SD 129.0)) compared to the control group (Sigma initial: mean 350.7 (SD 86.5) and final absolute change, mean -4.5 (SD 67.6)). The sizes of the extraocular muscles were reduced in the treatment group (mean (inferior rectus initial values): 1.3 (0.7), final percentage change: -13.2 (25.7), medial rectus initial values: 1.2 (0.6), final percentage change: -8.2 (20.7), superior rectus-levator palpebrae initial values: 1.2 (0.6), final percentage change: -9.5 (29.1), lateral rectus initial values: 1.0 (0.4), final percentage change: -11.5 (20.6)) compared to the control group (inferior rectus initial values: 0.9 (0.3), final percentage change: -4.0 (21.5), medial rectus initial values: 0.9 (0.3), final percentage change: 0.6 (22.4), superior rectus-levator palpebrae initial values: 0.9 (0.3), final percentage change: 12.5 (37.5), lateral rectus initial values: 0.9 (0.4), final percentage change: -0.5 (31.6)). Both measurements (degree of diplopia and muscle thickness) were statistically significant between groups (initial - final). No systemic or ocular adverse effects were found. CONCLUSIONS: Triamcinolone administered as a periocular injection is effective in reducing diplopia and the sizes of extraocular muscles in TAO ophthalmopathy of recent onset. This form of treatment is not associated with systemic or ocular side effects.     

Colon cancer proliferating desulfosinigrin in wasabi (Wasabia japonica)

A reduced incidence of different types of cancer has been linked to consumption of Brassica vegetables, and there is evidence that glucosinolates (GSLs) and their hydrolysis products play a role in reducing cancer risk. Wasabi (Wasabia japonica) and horseradish (Armoracia rusticana), both Brassica vegetables, are widely used condiments both in Japanese cuisine and in the United States. Desulfosinigrin (DSS) (1) was isolated from a commercially available wasabi powder and from fresh wasabi roots. Sinigrin (2) was isolated from horseradish roots. DSS and sinigrin were evaluated for their inhibitory effects on cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, on lipid peroxidation, and on the proliferation of human colon (HCT-116), breast (MCF-7), lung (NCIH460), and central nervous system (CNS, SF-268) cancer cell lines. DSS did not inhibit COX enzymes or lipid peroxidation at 250 microg/ml. Sinigrin inhibited lipid peroxidation by 71% at 250 microg/ml. However, DSS promoted the growth of HCT-116 (colon) and NCI H460 (lung) human cancer cells as determined by the MTT assay in a concentration-dependent manner. At 3.72 microg/ml, a 27% increase in the number of viable human HCT-116 colon cancer cells was observed; the corresponding increases at 7.50 and 15 microg/ml were 42 and 69%, respectively. At 60 microg/ml, DSS doubled the number of HCT-16 colon cancer cells. For NCI H460 human lung cancer cells, DSS at 60 microg/ml increased the cell number by 20%. Sinigrin showed no proliferating effect on the tumor cells tested. This is the first report of the tumor cell-proliferating activity by a desulfoglucosinolate, the biosynthetic precursor of GSLs found in Brassica spp.