Gastric mucosal blood flow and hepatic perfusion index in patients with portal hypertensive gastropathy

Endoscopic laser Doppler velocimetry is a simple non-invasive method to measure gastric mucosal blood flow. The present study is an attempt to determine a correlation, if any, between gastric mucosal blood flow and the hepatic perfusion index in patients with portal hypertensive gastropathy and their relationship to the severity of liver disease. Thirty patients with portal hypertensive gastropathy due to cirrhosis of the liver (eight class A, 13 class B, nine class C, according to Child-Pugh Classification) and six normal subjects were recruited into the study. In all subjects, the gastric mucosal blood flow and venous vasomotor reflex response was measured at two sites: the lesser and greater curvature, using endosoopic laser Doppler velocimetry. The hepatic perfusion index was measured using dynamic liver scintigraphy. The hepatic perfusion index (ratio of arterial/portal venous perfusion) in normal subjects and patients with portal hypertensive gastropathy belonging to Child-Pugh class A, B and C were 0.36 ± 0.02, 0.53 ± 0.08, 0.62 ± 0.14 and 1.04 ± 0.28, respectively. The gastric mucosal blood flow was similar in Child's A, B and C cases, while the venous vasomotor reflex response was reduced according to the Child-Pugh score (Child's A 37.4 ± 5.4%, normal control 62.3 ± 10.9%, Child's B 38.3 ± 18.2%, Child's C 22.5 ± 15.2%) and was statistically significant. The gastric mucosal blood flow and hepatic perfusion index are inversely correlated. The hepatic perfusion index altered with grading of cirrhotic change. This study confirms that the severity of portal hypertensive gastropathy is correlated with Child-Pugh score.     

The immunogenicity of Haemophilus influenzae: Meningococcal protein conjugate vaccine in Polynesian and non-Polynesian New Zealand infants

To examine the comparative immunogenicity of the Haemophilus influenzae type b-meningococcal protein (PRP-OMP) conjugate vaccine in Polynesian and non-Polynesian New Zealand infants.

Methodology:

Fifty-six Polynesian and 53 non-Polynesian infants aged 2–7 months recruited from primary health care settings in Auckland received a two-dose primary series of PRP-OMP. A sub-sample of 83 participants received a booster dose of PRP-OMP at 12–16 months of age. Anti-PRP antibody concentrations were measured in pre- and post-vaccination blood samples.

Results:

Antibody responses consistent with long-term protection (≥1.00 μg/mL) were observed in 72, 85 and 95% of children following the first, second and booster doses.

Conclusions:

Despite differences in disease epidemiology, PRP-OMP was highly immunogenic in Polynesian and non-Polynesian infants.     

Characterisation of renal chloride channel, CLCN5, mutations in hypercalciuric nephrolithiasis (kidney stones) disorders

Mutations of the renal-specific chloride channel (CLCN5) gene, which is located on chromosome Xp11.22, are associated with hypercalciuric nephrolithiasis (kidney stones) in the Northern European and Japanese populations. CLCN5 encodes a 746 amino acid channel (CLC-5) that has approximately 12 transmembrane domains, and heterologous expression of wild-type CLC-5 in Xenopus oocytes has yielded outwardly rectifying chloride currents that were markedly reduced or abolished by these mutations. In order to assess further the structural and functional relationships of this recently cloned chloride channel, additional CLCN5 mutations have been identified in five unrelated families with this disorder. Three of these mutations were missense (G57V, G512R and E527D), one was a nonsense (R648Stop) and one was an insertion (30:H insertion). In addition, two of the mutations (30:H insertion and E527D) were demonstrated to be de novo, and the G57V and E527D mutations were identified in families of Afro-American and Indian origin, respectively. The G57V and 30:H insertion mutations represent the first CLCN5 mutations to be identified in the N-terminus region, and the R648Stop mutation, which has been observed previously in an unrelated family, suggests that this codon may be particularly prone to mutations. Heterologous expression of the mutations resulted in a marked reduction or abolition of the chloride currents, thereby establishing their functional importance. These results help to elucidate further the structure-function relationships of this renal chloride channel.      

Radioresistant malignant myoepithelioma of the breast with high level of ataxia telangiectasia mutated protein

Malignant myoepithelioma of the breast (MMB) is a rare and often aggressive disease with poor prognosis. Little is known regarding its optimal treatment and progression. We describe the clinical history of a woman following excision of a benign adenomyoepithelioma which recurred years later as a radioresistant malignant myoepithelioma with high levels of ataxia telangiectasia mutated protein and mutant p53 (Cys135Phe). MMB requires close follow‐up and aggressive treatment. If adjuvant radiotherapy is adopted to improve local control, minimal postoperative delay and higher doses than for standard post‐mastectomy radiation are recommended.     

Dendritic cell generation and CD4+CD25HIGHFOXP3+ regulatory T cells in human head and neck carcinoma during Radio-chemotherapy

Background

Regulatory T cells (Treg) and dendritic cells (DC) play an important role in tumor immunity and immune escape. However, their interplay and the effects of anti-cancer therapy on the human immune system are largely unknown.

Methods

For DC generation, CD14⁺ monocytes were enriched by immunomagnetic selection from peripheral blood of advanced head and neck squamous cell carcinoma (HNSCC) patients and differentiated into immature DC using GM-SCF and IL-4. DC maturation was induced by addition of TNFα. The frequency of CD4⁺CD25^highF0XP3⁺ Treg in HNSCC patients was analyzed before and after radio-chemotherapy (RCT) by four-color flow cytometry.

Results

In HNSCC patients, the frequency of Treg (0.33 ± 0.06%) was significantly (p = 0.001) increased compared to healthy controls (0.11 ± 0.02%), whereas RCT had variable effects on the Treg frequency inducing its increase in some patients and decrease in others. After six days in culture, monocytes of all patients had differentiated into immature DC. However, DC maturation indicated by CD83 up-regulation (70.7 ± 5.5%) was successful only in a subgroup of patients and correlated well with lower frequencies of peripheral blood Treg in those patients.

Conclusion

The frequency of regulatory T cells is elevated in HNSCC patients and may be modulated by RCT. Monocyte-derived DC in HNSCC patients show a maturation deficiency ex vivo. Those preliminary data may have an impact on multimodality clinical trials integrating cellular immune modulation in patients with advanced HNSCC.