Intriguing issues of EGFR targeting in head and neck cancer

We have read the recent comprehensive review by Cruz et al.[1] regarding the targeting of receptor tyrosine kinases andtheir therapeutic perspectives in head and neck squamous cellcarcinomas (HNSCC). The major focus of this report was epidermalgrowth factor receptor (EGFR) biology and targeting. However,we feel     

Spray-dried microspheres based on methylpyrrolidinone chitosan as new carrier for nasal administration of metoclopramide.

The work purpose was to study the application of 5-methylpyrrolidinone chitosan (MPC) for preparing mucoadhesive microparticles for the nasal administration of drugs. Microspheres were produced by the spray-drying technique using MPC; metoclopramide hydrochloride (MC) was chosen as model drug. Chitosan microparticles were prepared as a comparison. The microparticles obtained were characterised (encapsulation efficiency, morphology, size and drug release behaviour). In-vitro mucoadhesive tests, swelling tests and ex-vivo studies using sheep nasal mucosa were performed. The hydrogel formation from microspheres was studied in different media and at different pHs. Microspheres are able to control the in-vitro MC release. MPC microparticles show good in-vitro mucoadhesive properties and ex-vivo controlled permeation profiles. The hydrogel formation is dependent mainly on the medium used: ionically crosslinked hydrogel was hypothesized. These in-vitro and ex-vivo preliminary results show that spray-dried microspheres based on MPC could be a suitable nasal delivery system for the administration of metoclopramide.     

Chromosomal abnormalities and microsatellite instability in sporadic endometrial cancer

Defective DNA mismatch repair and nonfunctional mechanisms controlling the proper progression of the cell cycle have been proposed as being responsible for the genomic instability and accumulation of karyotypic alterations in endometrial cancer (EC). To assess whether numerical chromosomal anomalies (aneuploidy) and microsatellite instability (MSI) might be representative of distinctive tumour behaviour, paraffin-embedded tissue samples from 86 patients with sporadic EC were evaluated by both fluorescence in situ hybridisation (FISH) and microsatellite analysis, using free nuclei and genomic DNAs (respectively). Approximately one-third of the tumours analysed (24/74; 32%) exhibited MSI, whereas 38/86 (44%) of the EC samples displayed aneuploidy. The majority of the unstable cases (15/24; 63%) were from advanced-stage patients. Conversely, 23 (61%) out of the 38 tumours with aneuploidy were from early-stage patients. No apparent correlation was found between MSI and aneuploidy, whereas the immunohistochemical (IHC) analysis revealed that inactivation of the MLH1 mismatch repair gene may be involved in the majority of the MSI+ sporadic ECs. No genetic or cytogenetic alteration analysed here seems to add any significant predictive value to the stage of disease.     

Definition of the role of chromosome 9p21 in sporadic melanoma through genetic analysis of primary tumours and their metastases. The Melanoma Cooperative Group

Malignant melanoma (MM) is thought to arise by sequential accumulation of genetic alterations in normal melanocytes. Previous cytogenetic and molecular studies indicated the 9p21 as the chromosomal region involved in MM pathogenesis. In addition to the CDKN genes (p16/CDKN2A, p15/CDKN2B and p19(ARF), frequently inactivated in familial MM), widely reported data suggested the presence within this region of other melanoma susceptibility gene(s). To clearly assess the role of the 9p21 region in sporadic melanoma, we evaluated the presence of microsatellite instability (MSI) and loss of heterozygosity (LOH) in primary tumours as well as in synchronous or asynchronous metastases obtained from the same MM patients, using 9 polymorphic markers from a 17-cM region at 9p21. LOH and MSI were found in 27 (41%) and 11 (17%), respectively, out of 66 primary tumours analysed. In corresponding 58 metastases, MSI was found at higher rate (22; 38%), whereas a quite identical pattern of allelic deletions with 27 (47%) LOH+ cases were observed. Although the CDKN locus was mostly affected by LOH, an additional region of common allelic deletion corresponding to marker D9S171 was also identified. No significant statistical correlation between any 9p21 genetic alteration (LOH, MSI or both) and clinicopathological parameters was observed.     

Myelin thickenings in val 102/fs null mutation of MPZ gene

Painful sensory neuropathies consist of a wide range of neuropathies that can involve large as well as small nerve fibres. Even if most cases remain of unknown cause, some of them may be associated with an underlying disorder such as diabetes, HIV, infections, amyloidosis, and Sjogren's syndrome. Since in some cases an autoimmune mechanism has been postulated, we investigated a panel of circulating autoantibodies including anti‐gliadin (AGA), anti‐endomysium (EmA), anti‐transglutaminase (tTGA) and anti‐nuclear (ANA) antibodies in the sera of patients with unexplained painful sensory neuropathies in order to identify other potentially treatable disorders. We tested the sera of 10 patients (4M; 6F) previously investigated for other causes of neuropathies, including anti‐nerve, onconeural, anti‐extractable nuclear, anti‐neutrophil cytoplasmic, anti‐thyroglobulin (TgA) and anti‐peroxidase (TPOA) antibodies. We found the presence of AGA positivity in 4 patients (40%), ANA in 7 (70%) and AGA + ANA in 4 (40%), two of whom were negative for celiac disease by gastrointestinal biopsy. None of the patients had EmA positivity. Three (30%) had TgA and TPOA and none had anti‐nerve or onconeural antibodies. Whether the presence of circulating autoantibodies in patients with unexplained painful neuropathy reflects an autoimmune involvement which may be amenable to immune therapy and not only to symptomatic treatment remains to be established.     

Control of homozygous β-thalassemia by carrier screening and antenatal diagnosis in Sardinians

This paper reports the present results of an ongoing program aimed at preventing homozygous beta-thalassemia by means of heterozygote screening and antenatal diagnosis in the Sardinian population. Screening based on the knowledge of carrier frequency and types of thalassemia prevalent in this population was designed to discover all heterozygotes except the few silent beta-thalassemia carriers. Most of the couples at risk were informed and accepted testing. Information was conveyed by mass media, midwives and marriage registry offices. Antenatal diagnosis was accepted by the majority of the couples counselled. The results of antenatal testing were very accurate. There was only one misdiagnosis out of 949 pregnancies tested. This risk of fetal loss was 7.5%. The program was highly effective, as shown by the decline of the incidence of the homozygous state from 1:205 live births in 1976 to 1:557 in 1981.     

Neuropsychological rehabilitation in a case of Cornelia de Lange syndrome

Cornelia de Lange syndrome is a rare congenital disorder. Symptoms include a characteristic facial structure, pre- and post-natal growth deficiency, hypertrichosis, and visceral and cardiovascular anomalies. Behavioural problems and moderate to severe mental retardation are also present. In this paper, we report a mild case of Cornelia de Lange syndrome. The neuropsychological rehabilitation of this patient is also described. It was structured on the patient's specific areas of strength and weakness in order to facilitate the development of adaptive cognitive abilities. To maximise the learning potential of these children, we recommend specific interventions with a multidimensional neuropsychological approach, which considers developmental abilities and disabilities as related to the global reality of the child.     

Multi-detector computed tomography angiography of the hepatic artery in liver transplant recipients

Purpose: To evaluate the ability of multi-detector row computed tomography angiography (CTA) in detecting hepatic artery complications in the follow-up of liver transplant patients, performing volume-rendering as reconstruction technique.

Material and Methods: The anatomy of hepatic artery was studied in 27 liver transplant recipients with a four-row CT scanner using the following parameters: collimation, 1 mm; slice width, 1 mm; table feed, 6-8 mm/s; spiral reconstruction time, 0.5 s; reconstruction interval, 0.5 mm; mAs, 160; kVp, 120. Before the study, the patients received 1000 ml of water as oral contrast agent to produce negative contrast in the stomach and the small bowel. A non-ionic contrast medium was infused intravenously at a rate of 5 ml/s with a bolus tracking system. Volume-rendering of hepatic artery was performed with the 3D Virtuoso software.

Results: The celiac trunk, the hepatic artery, and the right and left hepatic arteries were successfully displayed in high detail in all patients. Side branches, including small collaterals, and hepatic artery anastomosis could also be readily visualized. Volume-rendered CTA detected six hepatic artery stenoses, two hepatic artery thromboses, and two intrahepatic pseudoaneurysms. In two cases, CT detected hepatic artery stenosis with a diameter reduction of less than 50%, while digital subtraction angiography showed a normal artery.

Conclusion: Volume-rendered multi-detector CTA is a promising non-invasive technique, since it allows images of high quality to be generated with excellent anatomical visualization of the hepatic artery and its complications in liver transplant recipients.     

The incidence of female genital tumors in the Province of Sassari in the period 1992-2000

The incidence of gynecologic tumors in the Province of Sassari in the period 1992-2000 has been studied in order to estimate their value and to make a comparison with the data of the period 1974-83. The analysis of our data regarding the period 1992-2000, if compared with those of the previous period 1974-83, showed a change in the percentage distribution of all gynecologic tumors, with an increase in the incidence of malignant tumors of the ovary (from 17.1% to 28.0%) and a reduction in the incidence of endometrial carcinoma (from 52.1% to 45.0%). Cervix cancer seemed stationary with a mild reduction (from 26.8% to 23.0%). The data showed, with regard to the incidence per 100,000, an increase of endometrial carcinoma (19.05 per 100,000 vs 11.99 per 100,000) and malignant ovarian tumor (11.99 per 100,000 vs 3.95 per 100,000). Our data reported a worrying increase of hormonal-dependent tumors in North Sardinia such as endometrial and ovarian cancer with the highest increase in malignant ovarian tumors. In comparison to the previous period we confirmed a historically low incidence of cervical and external genitalia tumors (vulva and vagina) in North Sardinia.