Brain nitric oxide changes after controlled cortical impact injury in rats

Nitric oxide (NO) and the NO end products, nitrate and nitrite, were measured at the impact site after a 5-m/s, 3-mm deformation controlled cortical impact injury in rats. Immediately after the impact injury and the NO and microdialysis probes could be replaced, there was an increase from baseline in NO concentration of 83 +/- 16 (SE) nM, compared with 0.5 +/- 4 nM in the sham injured animals (P < 0.001). This marked increase in NO occurred at the time of the initial rise in blood pressure (BP) and intracranial pressure (ICP) in response to the injury. After the initial increase in BP and ICP, the BP decreased and stabilized at a value which was approximately 20 mmHg below the preinjury values, and ICP plateaued at an average value of 20 mmHg, compared with 8 mmHg in the sham-injured animals. This provided an average cerebral perfusion pressure of 40-50 mmHg, compared with 65-75 mmHg for the sham-injured animals. These values were relatively constant for the remainder of the 3-h monitoring period. The NO values also stabilized during this time period. By 1 h after the impact injury the NO concentration measured directly using the NO electrode had decreased from baseline values by an average value of 25 +/- 6 nM. NO concentration remained significantly lower than baseline values throughout the remainder of the 3-h monitoring period. The concentration of nitrate/nitrite in the dialysate fluid also decreased by an average value of 341 +/- 283 nM 20-40 min after the injury. Dialysate nitrite/nitrate concentrations remained less than the preinjury baseline values throughout the remainder of the 3-h monitoring period. Preinjury treatment with L-nitro-arginine methyl ester (L-NAME) blunted the injury-induced increase in NO and resulted in more severe immediate intracranial hypertension and more severe systemic hypotension at one hour after injury. Mortality was also 67% with L-NAME pretreatment, compared with 1% in untreated animals.     

Immunohistochemical localization of metallothionein in cell nucleus and cytoplasm of fetal human liver and kidney and its changes during development

The distribution of metallothionein (MT) during human development was investigated using both immunohistochemical and biochemical methods. The level of MT in the fetal liver was higher than the adult liver levels. Higher levels of zinc (Zn) and copper (Cu) were also detected in the fetal liver compared to the adult liver. Although cadmium (Cd) was present in detectable levels in the human adult liver, none was detected in the human fetal liver. MT was localized in the nucleus and the cytoplasm of human fetal and neonatal hepatocytes, using a specific rabbit antibody raised to rat liver MT. In the adult human liver cells, MT was localized mainly in the cytoplasm. In the fetal and neonatal human kidney, MT was localized mainly in the nucleus and the cytoplasm of the proximal tubular epithelial cells. In the adult kidney, in addition to nuclear-cytoplasmic localization of MT, intraluminal localization was also observed.     

5 years after an ACE: what happens then?

Purpose

Antegrade continence enema (ACE) revolutionised the lives of children with chronic constipation and soiling. Parents often ask how long the ACE will be required. We looked at our patients 5 years after ACE formation to answer the question.

Methods

We reviewed clinical notes of all patients undergoing ACE procedure during January 1990 to December 2010. Only patients with >5 years follow-up were included. Data are given as median (range).

Results

133 patients were included with >5 years of follow-up. Primary pathology was anorectal anomaly (ARA) 64 (48 %); spinal dysraphism (SD) 40 (30 %); functional constipation (FC) 14 (10 %); Hirschsprung’s Disease (HD) 10 (8 %) and others 5 (4 %). Median follow-up was 7 years (5–17 years). Overall 74 % still use their ACE; whilst 26 % no longer access their stoma, of whom 47 % recovered normal colonic function. 50 % of HD patient recover colonic function. FC has the highest failure rate at 21 %.

Conclusions

Overall 86 % achieved excellent clinical outcome with 74 % of patient still using their ACE at 5 years. HD has the highest recovery rate of 50 %. FC has a more unreliable clinical outcome with 21 % recovered colonic function and 21 % failed. Outcome varied dependent on the background diagnosis.

     

Cardiomediastinal tamponade and shock following three-stage transthoracic oesophagectomy

Massive gastric tube dilatation causing cardiomediastinal tamponade is an unusual cause of obstructive shock after transthoracic oesophagectomy. A 55-year-old female was operated for total transthoracic oesophagectomy. Twelve hours after the surgery, she developed hypotension and raised central venous pressure unresponsive to fluid infusion and ionotropes. X-ray chest showed a massively dilated stomach, which was causing intrathoracic tamponade. Suction applied to the nasogastric tube led to aspiration of 150-200 ml of fluid and a large volume of air, which led to resolution of the haemodynamic instability. A simple manoeuvre like nasogastric suction in postoperative case of oesophagectomy can serve as a diagnostic as well as therapeutic tool. It must be performed before resorting to invasive and expensive examination or intervention.     

Effect of age and sex on liver damage due to excess dietary copper in Fischer 344 rats

OBJECTIVE: The aim of this study was to investigate the morphologic and biochemical effects of excess dietary copper in young and adult rats of different sex. METHODS: Adult Fischer 344 male and female rats were given a diet containing 1500 ppm copper for 18 weeks. Young male and female rats were fed a similar copper-loaded diet from birth until 16 weeks of age. Age- and sex-matched control rats were fed a normal rodent diet (<10 ppm copper). Serum liver enzyme activity was determined in all rats. Livers were sampled for histology, histochemistry (rhodanine), immunohistochemical detection of metallothionein and copper analysis by atomic absorption spectrophotometry. Hepatic metallothionein and zinc concentrations were measured in adult rats. RESULTS: Excess dietary copper caused substantial liver injury, as evidenced by morphologic changes and increased activity of serum ALT, GGT, and SDH. All copper-loaded rats had significantly (p< 0.05) increased hepatic copper concentrations compared to controls. However, young copper-loaded rats accumulated more hepatic copper, had more severe liver changes, and had higher serum liver enzyme activities than adult rats. Histologic changes in copper-loaded rats consisted of multifocal hepatitis and widespread single-cell necrosis. Cytoplasmic copper was detected histochemically in centroacinar zone 1 (portal) and mid-zone in copper-loaded rats. Immunoreactivity for metallothionein was prominent in necrotic hepatocytes and within inflammatory foci in copper-loaded rats. However, differences in hepatic metallothionein concentrations were not detected between adult copper-loaded and control rats. CONCLUSIONS: Young Fischer 344 rats are more susceptible than adults to copper-induced liver injury.     

Leads to cancer control based on cancer patterns in a rural population in South India

Objective: Cancer patterns and incidence rates for a rural population (359,674) resident in 384 villages spread over 2058 km² in Palani and Oddanchathram taluks of Dindigul District, Tamil Nadu, in South India, are described in this paper. Methods: A population-based cancer registry was established in 1995 to register incident invasive and in-situ cancers. Cases were found and details abstracted by cancer registry staff visiting 26 data sources, comprising cancer hospitals, tertiary and secondary care hospitals, pathology laboratories and death registration offices. A customized version of CANREG-3 software was used for data entry and analysis. Results: During the period 1996–1998, 783 invasive cancers (310 male and 473 females) were registered, yielding an all-cancer crude incidence rate of 56.8/100,000 males and 88.5/100,000 females; the corresponding age standardized incidence rates (ASR) were 83.3 and 122.3 respectively. In males, mouth cancer (ASR 11.5) was the most frequently recorded malignancy followed by tongue (ASR 8.6), hypopharynx (ASR 7.8), esophagus (ASR 7.8) and larynx (ASR 7.8). Thus head and neck cancers accounted for half of the male cases. In females, cervical cancer (ASR 65.4) accounted for more than half of the cancers followed by breast (ASR 14.2) and mouth (ASR 10.2). Ambillikai Cancer Registry (ACR) reports the second highest incidence of cervical cancer in the world. More than four-fifths of cervical cancer cases were diagnosed in stages II B and III B; a third of these cancer patients either did not have, or did not complete, treatment. Conclusions: The observed cancer patterns in this population establish that measures directed at prevention and early detection (linked with treatment) of cervix and head and neck cancers are of paramount importance for cancer control in this and other rural populations of India where three-fourths of the total population live.