Differential immunoreactivity of her-2/neu oncoprotein in prostatic tissues.

To investigate HER-2/neu oncoprotein immunoreactivity, monoclonal antibody TA1 immunohistochemical examination of flash-frozen radical prostatectomy specimens was performed (n = 35). All prostatic specimens contained benign prostatic hyperplasia (BPH) and/or prostatic intraepithelial neoplasia (PIN), as well as prostatic carcinoma (CaP). HER-2/neu oncoprotein immunoreactivity in BPH tissues was not significantly different than that for the PIN basal cell layer (P = 0.10) or for the PIN luminal cells (P = 0.17). There was significantly more HER-2/neu oncoprotein immunoreactivity in BPH than in areas of CaP (P < 0.001). There was no significant difference in the amount of immunoreactivity present in PIN basal cells when compared to the PIN luminal cells (P = 0.49). Both the PIN basal cells and luminal cells stained for the HER-2/neu oncoprotein to a higher degree than cells in the CaP areas (P < 0.001 in both cases). HER-2/neu oncoprotein immunoreactivity is present at a significantly higher degree in BPH and PIN than in malignant prostatic epithelium.     

Congenital disorder of glycosylation type 1a: three siblings with a mild neurological phenotype.

We report 3 siblings (1 male and 2 female) recently diagnosed with congenital disorder of glycosylation type Ia (CDG-Ia) in their mid-20s. They experience mild mental retardation but manage to function independently in society. Their professions are library assistant, professional artistic painter and secretarial work. All three siblings have cerebellar hypoplasia and ataxia, but are able to ambulate easily. Two of the siblings have required strabismus surgical repairs. All have antithrombin III deficiency, osteoporosis, and mild dysmorphic features. Hypergonadotrophic hypogonadism was a feature of the two female siblings. A type 1 sialotransferrin pattern and phosphomannomutase (PMM) deficiency have been demonstrated. They are compound heterozygotes for R141H and L32R mutations in the PMM2 gene. While there is clinical heterogeneity in CDG-Ia, we believe that our patients are among the mildest of intellectually affected CDG-Ia patients reported to date.     

The expression of somatostatin receptors 1 and 2 in benign,pre‐malignant and malignant laryngeal lesions

The expression of somatostatin receptors 1 and 2 in benign, pre‐malignant and malignant laryngeal lesions The role of chemotherapy in squamous cell carcinoma of the larynx has not been clearly defined. Whilst toxic chemotherapy regimes may confer a marginal improvement in survival, surgery and radiotherapy remain the mainstay of treatment. Somatostatin is a naturally occurring peptide, which exerts antiproliferative and antiangiogenic effects via five membrane‐bound receptor subtypes. The expression of somatostatin receptor subtypes (SSTRs) 1 and 2 was studied in benign, pre‐malignant and malignant laryngeal specimens. Epithelial expression of SSTR1 was detected in 4/6 (67%) Reinke's oedema, 5/6 (83%) pre‐malignant and 8/12 (67%) malignant specimens, with virtually no stromal or vascular expression. High levels of epithelial SSTR2 expression were noted in all Reinke's oedema specimens, compared with low‐to‐moderate levels in only 2/6 (33%) pre‐malignant and 3/12 (25%) malignant specimens (P < 0.01). This ‘loss’ of epithelial SSTR2 expression may provide a growth advantage in pre‐malignant and malignant laryngeal lesions. Vascular expression of SSTR2 was ubiquitous in all groups, with scant stromal expression. Overall, most (>80%) pre‐malignant and malignant laryngeal specimens expressed at least one of the two SSTR subtypes studied. Somatostatin analogues may have a therapeutic role in squamous cell carcinoma of the larynx.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Sensitivity and specificity of screening for Down syndrome with alpha-fetoprotein, hCG, unconjugated estriol, and maternal age.

The sensitivity and specificity of maternal serum screening for Down syndrome with different biochemical markers were evaluated. Detection rates with different combinations of maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (uE3) were established by retrieving and analyzing 54 serum specimens from women with confirmed Down syndrome pregnancies, compared with 657 specimens from women with normal outcomes. With a risk cutoff of 1:270 at the second trimester, the detection rate with MSAFP, hCG, and uE3 was two to three times higher than with MSAFP alone. With all three markers, the detection rate for Down syndrome increased from 50 to 77% as maternal age increased, and was 60% in a representative screened population. If uE3 was omitted, the detection rate decreased from 60 to 48%. One thousand women were screened prospectively, either with MSAFP or with all three markers prospectively, either with MSAFP or with all three markers and 4.1% with MSAFP. With the three markers, the positive predictive value for Down syndrome was 2.2% overall and as high as 5.9% in older women. Therefore, the addition of hCG and uE3 to the maternal serum screen increases the positive predictive value by 50-300%, depending on maternal age. These results confirm the efficacy of screening for Down syndrome using maternal age and three serum markers.     

Leukocyte Depletion of Blood Cardioplegia Attenuates Reperfusion Injury

Background. Leukocytes are associated with myocardial injury during reperfusion after ischemia. Short periods of leukocyte depletion during reperfusion result in persistent attenuation of postischemic myocardial dysfunction.

Methods. Leukocyte depletion was examined in a canine model of regional myocardial ischemia and reperfusion. The extracorporeal circuit and cardioplegia circuits underwent leukocyte depletion by mechanical filtration. Animals were instrumented for baseline global function before 90-minute occlusion of the left anterior descending coronary artery. Global function during ischemia and at 5, 30, 60, and 90 minutes after a 60-minute cardioplegic arrest using continuous blood cardioplegia was assessed in leukocyte-depleted (n = 9) and control (n = 10) groups.

Results. No significant difference between groups was seen for systemic leukocyte counts, global function, or water content. Endothelial function was significantly protected as assessed by response to both calcium ionophore (endothelial-dependent, receptor-independent relaxation: leukocyte-depleted, 72% ± 19% of endothelin-induced constriction versus control, 46% ± 14%; p < 0.05) and acetylcholine (endothelial-dependent, receptor-dependent relaxation: leukocyte-depleted, 83% ± 11% versus control, 44% ± 15%; p < 0.05).

Conclusions. Leukocyte-mediated endothelial reperfusion injury can be attenuated by leukocyte depletion during reperfusion.     

Diet and disadvantage: observations on infant feeding from an inner city

Background: There are few detailed nutritional studies analysing dietary intakes and weaning practices of inner city infants aged 0–12 months. Pasteurized cow's milk (PCM) is not recommended as a main drink until after 1 year of age, although early usage is still common. Premature introduction of pasteurized cow's milk is associated with increased risk of iron deficiency anaemia. Methods: We therefore prospectively examined the dietary effect of early introduction of pasteurized cow's milk on the nutritional intake of 100 infants (mean age at recruitment 7.8 months), whose mothers had already elected to introduce cow's milk before the recommended age of 12 months in a deprived inner city area. In addition, a retrospective questionnaire on feeding practices and food choices was administered and information on parental education and employment was collected, together with a 3-day dietary diary of weighed intakes at recruitment. Results: The results indicate that weaning practices are handed down from family and friends and are intuitive rather than informed. Over 80% of the infants had intakes of iron, zinc and vitamin D below the reference nutrient intake (RNI) and a further 41% had low vitamin C intakes. Prior to introduction of PCM, there was also misuse of infant formula. Twenty per cent added an extra scoop of powder to the feeds, 10% added milk powder to the bottle before addition of water and 30% used microwave ovens to heat the infant bottle. Conclusion: Feeding practices in a deprived inner city area differed substantially from guidelines and infants were at risk of developing nutrient deficiencies as well as poor feeding practices.