Abnormal heart rate variability in adults with growth hormone deficiency

GH-deficient (GHD) patients have increased risk of cardiovascular death and may have cardiac structural abnormalities. In non-GHD patients these are associated with cardiac autonomic dysfunction, and it is possible that autonomic dysfunction is also present in GHD patients. Power spectral analysis (PSA) of heart rate variability (HRV) indirectly measures cardiac autonomic tone and generates peaks at 3 frequency bands, very low frequency (VLF), low frequency (LF) and high frequency (HF). The area under the LF curve is considered to reflect predominantly cardiac sympathetic activity, whereas HF indicates parasympathetic activity. PSA of HRV was performed in 14 normotensive GHD patients (5 men and 9 women; mean age, 35.2 yr) and 19 healthy controls (9 men and 10 women; mean age, 38.3 yr). GHD patients had 26% lower normalized LF power (P < 0.004), 39% higher normalized HF power (P < 0.001), 28% lower normalized VLF power (P < 0.046), and 51% lower LF/HF ratio (an index of sympathovagal balance; P < 0.001) compared to controls. These data indicate that heart rate variability is abnormal in patients with GHD. The decreased sympathetic tone could be a consequence of reduced central sympathetic tone or altered cardiac responsiveness to autonomic control and may contribute to the increased cardiovascular risk in GHD patients.     

Life Table analysis of stomal complications following colostomy

PURPOSE: This study was designed to evaluate the longterm complication rate of left iliac fossa end sigmoid colostomies and to determine etiologic factors. METH-ODS: A retrospective chart review and actuarial analysis were performed. RESULTS: The crude and actuarial risks of paracolostomy complications in 203 patients were 51.2 percent and 58.1 percent at 13 years, respectively. Paracolostomy hernia was the most common complication (36.7 percent at 10 years). Siting the stoma through the belly of the rectus abdominis muscle did not reduce the risk of hernia, but an extraperitoneal course had a significantly lower risk of herniation when compared with a transperitoneal course and intestinal obstruction was marginally less frequent. Paracolostomy hernias were otherwise more likely in the elderly, and in those with other abdominal wall hernias. Mesenteric fixation did not reduce the subsequent chance of prolapse. The reduction in the risk of intestinal obstruction when lateral space closure was employed was not statistically significant (4 percent vs. 10 percent,P < 0.1), and all three patients with stomal retraction had had lateral space closure. CONCLUSION: The evidence in this study that spans a 22-year period questions much surgical technical dogma and raises the possibility that parastomal hernias may, like inguinal hernias, represent a failure in the transversalis fascia that might technically be avoidable.     

Reye-Like Syndrome Due to Margosa Oil Poisoning: Report of a Case with Postmortem Findings

A syndrome similar to Reye's syndrome has been reported in infants and mice after ingestion of margosa oil. Although aflatoxin contamination of the oil has been recognized, autopsy findings in an infant with margosa oil poisoning reveal changes consistent with Reye's syndrome but unlike those described in acute aflatoxicosis. The toxic action of margosa oil may be due to the synergistic effects of aflatoxins and other toxic component(s) present in the oil.     

Extrahypothalamic growth-hormone-releasing factor (GRF) secretion is a rare cause of acromegaly: plasma GRF levels in 177 acromegalic patients

To assess the frequency with which acromegaly is caused by ectopic secretion of GRF, we collected plasma samples from 177 unselected acromegalic patients. The samples together with those of three acromegalic patients with previously diagnosed tumors secreting GRF and of normal subjects were assayed in 3 independent GRF RIAs. Plasma immunoreactive GRF (IR-GRF) levels in normal subjects were either undetectable or detectable at levels up to 62.5 pg/ml. In none of the 177 specimens from acromegalic patients were IR-GRF values detectable in all assays, and in the most sensitive assay, the levels were similar to those in normal subjects, with the highest level measuring 82 pg/ml. In contrast, plasma IR-GRF found in the 3 patients with tumors that secreted GRF ranged from 2.0-24.4 ng/ml. These data suggest that extrahypothalamic GRF secretion is a rare cause of acromegaly. However, it is important that this rare cause of acromegaly be diagnosed before the patient has unnecessary surgery and/or irradiation directed at the pituitary. We recommend that plasma IR-GRF be measured in each new acromegalic patient.     

Impact of tissue processing,archiving and enrichment techniques on DNA methylation yield in rectal carcinoma

Background

Formalin fixation, duration of tissue storage and tissue enrichment techniques can affect DNA methylation yield but these effects have not been quantitatively measured. The aim is to investigate the relative impact of these conditions on DNA methylation in rectal cancer.

Methods

10 rectal cancers with matched undissected fresh frozen tissues, laser capture microdissected (LCM) formalin-fixed paraffin-embedded (FFPE) tissues, manual macrodissected FFPE tissues, adjacent normal mucosa and stromal tissues were analysed for APC and LINE-1 methylation using bisulphite pyrosequencing.

Results

FFPE cancer tissues, which had been stored for at least 4 years showed similar APC and LINE-1 methylation changes to matched fresh frozen cancer tissues. Laser capture microdissection did not increase the degree of methylation detected compared to manual macrodissection. Analysis of stromal tissues showed that they had undergone significant methylation changes compared to adjacent macroscopically normal mucosa, but not to the same extent as cancer tissues.

Conclusion

Reliable DNA methylation results can be obtained from FFPE rectal cancer tissues, which have been in long-term storage. Because only minor differences in methylation between macrodissected and LCM cancer tissues were found, our results do not support the routine use of LCM to enrich for cancer cells for DNA methylation studies.