Complete maternal uniparental isodisomy of chromosome 4 in a subject with major depressive disorder detected by high density SNP genotyping arrays.

Uniparental isodisomy (iUPD) is a rare genetic condition caused by non-disjunction during meiosis that ultimately leads to a duplication of either the maternal or paternal chromosome in the affected individual. Two types of disorders can result, those due to imprinted genes and those due to homozygosity of recessive disease-causing mutations. Here, we describe the third known case of complete chromosome 4 iUPD of maternal origin. This condition became apparent during whole genome linkage studies of psychiatric disorders in the Portuguese population. The proband is an adult female with normal fertility and no major medical complaints, but a history of major depressive disorder and multiple suicide attempts. The proband's siblings and parents had normal chromosome 4 genotypes and no history of mood disturbance. A brief review of other studies lends support for the possibility that genes on chromosome 4 might confer risk for mood disorders. We conclude that chromosome 4 maternal uniparental disomy (UPD) is a rare disorder that may present with a major depressive phenotype. The lack of a common disease phenotype between this and two other cases of chromosome 4 iUPD [Lindenbaum et al. [1991] Am J Med Genet 49(Suppl 285):1582; Spena et al. [2004] Eur J Hum Genet 12:891-898) would suggest that there is no vital maternal gene imprinting on chromosome 4. However, since there is no reported case of paternal chromosome 4 UPD, paternal gene imprinting on chromosome 4 cannot be excluded.     

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.     

Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Influence of subacute starvation on cardiac response to isoproterenol in rats.

Several studies have reported that the heart is severely affected by chronic malnutrition. However, the influence of these alterations on cardiac function remains unclear. The aim of this study was to evaluate the effects of subacute starvation on the heart chronotropic response to a beta-adrenergic agonist (isoproterenol). Twelve rats were fed rat chow ad libitum or a 50%-restricted diet for 17 days. The rats were killed, the right atrium was isolated and incubated, and in vitro spontaneous cardiac contractions and frequency were registered. Cumulative doses of isoproterenol were added to the solution until maximal cardiac frequency was achieved. A deficit of 25% in the weight gain was observed in study rats compared with controls (92.6 +/- 10.2 vs. 113.8 +/- 19.2 g, p less than 0.05). Mean daily food intake was 4.8 +/- 0.1 and 9.8 +/- 0.5 g/day for semistarved and control rats, respectively. The in vitro cardiac frequency of the semistarved rats was similar to that of controls (290 +/- 15 and 305 +/- 23 beats/min, respectively, NS). However, when isoproterenol was added to the solution, maximal cardiac frequency of the semistarved rats (435 +/- 51 beats/min) was lower than that of control rats (508 +/- 34 beats/min, p less than 0.005). These findings suggest that subacute starvation may alter the cardiac response to beta-adrenergic agonists.