Accurate skin dose measurements using radiochromic film in clinical applications.

Megavoltage x-ray beams exhibit the well-known phenomena of dose buildup within the first few millimeters of the incident phantom surface, or the skin. Results of the surface dose measurements, however, depend vastly on the measurement technique employed. Our goal in this study was to determine a correction procedure in order to obtain an accurate skin dose estimate at the clinically relevant depth based on radiochromic film measurements.

Depletion of endogenous spinal 5-HT attenuates the behavioural hypersensitivity to mechanical and cooling stimuli induced by spinal nerve ligation.

There is compelling evidence for a strong facilitatory drive modulating spinal nociceptive transmission. This is in part via serotonergic pathways and originates from the rostroventral medulla. We previously demonstrated that neuropathic pain is associated with an enhanced descending facilitatory drive onto the mechanical evoked responses of dorsal horn neurones, mediated by 5-HT acting at spinal 5-HT3 receptors.

The genetics of HNPCC: application to diagnosis and screening.

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC; Lynch Syndrome) is the most common form of hereditary colorectal cancers. Predisposed individuals have increased lifetime risk of developing colorectal, endometrial and other cancers. The syndrome is primarily due to heterozygous germline mutations in one of the mismatch repair genes; mainly MLH1, MSH2, MSH6 and PMS2.

Oral gabapentin treatment for symptomatic Heimann-Bielschowsky phenomenon.

Purpose: To describe a patient with symptomatic Heimann-Bielschowsky phenomenon (HBP) treated successfully with oral gabapentin.

Design: Interventional case report.

Methods: A 57-year-old patient with retinitis pigmentosa had a 12-month history of vertical oscillopsia.

Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin.

Not all neuropathic pain patients gain relief from current therapies that include the anticonvulsant, gabapentin, thought to modulate calcium channel function. We report a neural circuit that is permissive for the effectiveness of gabapentin. Substance P-saporin (SP-SAP) was used to selectively ablate superficial dorsal horn neurons expressing the neurokinin-1 receptor for substance P.

Giant cell (temporal) arteritis: an overview and update.

Giant cell arteritis is a systemic disease that continues to be a sight-threatening medical emergency requiring prompt recognition and treatment in order to avoid devastating ophthalmic consequences. Although there have been advances in the genetic and immunologic understanding of the underlying pathogenesis of the disease, the exact etiology of the condition, to date, remains unclear. Visual manifestations of giant cell arteritis are the common mode of presentation, making the ophthalmologist critically responsible for early diagnosis and treatment.

Adenomatous polyposis families that screen APC mutation-negative by conventional methods are genetically heterogeneous.

Purpose: One third of families with classical adenomatous polyposis (FAP), and a majority of those with attenuated FAP (AFAP), remain APC mutation-negative by conventional methods. Our purpose was to clarify the genetic basis of polyposis and genotype-phenotype correlations in such families.

Patients And Methods: We studied a cohort of 29 adenomatous polyposis families that had screened APC mutation-negative by the protein truncation test, heteroduplex analysis, and exon-specific sequencing.

APC and beta-catenin protein expression patterns in HNPCC-related endometrial and colorectal cancers.

Objective: The adenomatous polyposis coli (APC) and beta-catenin (CTNNB1) genes are the two major components of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. The overactivation of the pathway, which results in abnormal accumulation of beta-catenin protein in nuclei, contributes to most colorectal cancers (CRCs), both sporadic and hereditary, as well as sporadic endometrial cancers (ECs). Here, we studied the involvement of APC and beta-catenin in hereditary nonpolyposis colorectal cancer (HNPCC)-related ECs, and compared the expression patterns to those in HNPCC-related CRCs.

Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome?

Purpose: Familial clustering of endometrial carcinoma (EC) may occur as part of hereditary nonpolyposis colorectal cancer (HNPCC), a multiorgan cancer syndrome with mismatch repair (MMR) deficiency. Clustering of EC alone, termed as familial site-specific EC, may constitute a separate entity. Because its genetic basis is unknown, our purpose was to characterize such families molecularly.

Neutron-activation revisited: the depletion and depletion-activation models.

The growth of a radioactive daughter in neutron activation is commonly described with the saturation model that ignores the consumption of parent nuclei during the radio-activation process. This approach is not valid when radioactive sources with high specific activities are produced or when the particle fluence rates used are very high. Assuming a constant neutron fluence rate throughout the activation target, a neutron-activation model that accounts for the depletion in parent nuclei is introduced.

Validation of Monte Carlo calculated surface doses for megavoltage photon beams.

Recent work has shown that there is significant uncertainty in measuring build-up doses in mega-voltage photon beams especially at high energies. In this present investigation we used a phantom-embedded extrapolation chamber (PEEC) made of Solid Water to validate Monte Carlo (MC)-calculated doses in the dose build-up region for 6 and 18 MV x-ray beams. The study showed that the percentage depth ionizations (PDIs) obtained from measurements are higher than the percentage depth doses (PDDs) obtained with Monte Carlo techniques.

Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations.

A considerable fraction of families with HNPCC shows no germline mismatch repair (MMR) gene mutations. We previously detected 'hidden' MMR gene defects in 42% of such families, leaving the remaining 58% 'truly' mutation negative. Here, we characterized 50 colorectal carcinomas and five adenomas arising in HNPCC families; 24 truly MMR gene mutation negative and 31 MMR gene mutation positive.

A case of facial swelling and proptosis.

A case of high-grade B cell lymphoma of the maxillary sinus in a 74-year-old Caucasian male patient is described. Initial presentation of the tumour commonly simulates odontogenic infection. Dental surgeons should maintain a high degree of suspicion for early diagnosis of maxillary sinus tumours.

Restoring mismatch repair does not stop the formation of reciprocal translocations in the colon cancer cell line HCA7 but further destabilizes chromosome number.

An important anticarcinogenic function of the mismatch repair (MMR) system is its role in preventing recombination between similar, but nonidentical (homeologous) sequences, thus preventing chromosomal rearrangements. We recently identified a novel chromosomal instability (CIN) phenotype in an MMR defective colon cancer cell line (HCA7) characterized by an ongoing tendency to multiple reciprocal chromosomal translocations. To analyse the relation between MMR and chromosomal changes more closely, the HCA7 stem clone was divided into three stocks.

Molecular basis and diagnostics of hereditary colorectal cancers.

Hereditary colorectal cancer syndromes are classified according to the presence of unusually large number of adenomatous or hamartomatous polyps, or their absence. The latter category includes hereditary non-polyposis colorectal cancer (Lynch syndrome) and its variants Muir-Torre and Turcot's syndromes. Adenomatous polyposis syndromes include familial adenomatous polyposis (FAP) and its variants, and the recently identified MYH- (mutY homolog)-associated polyposis.

Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury.

Pain resulting from peripheral nerve injury, characterised by ongoing pain, hyperalgesia and allodynia arises from peripheral and central processes. Here, we studied the potential role of central facilitations in nerve injury by investigating the effect of blocking the excitatory 5HT3 receptor with ondansetron. 5HT3 receptors play a pronociceptive role in the spinal cord and ondansetron has previously been shown to produce antinociception in behavioural studies.

HNPCC mutation MLH1 P648S makes the functional protein unstable, and homozygosity predisposes to mild neurofibromatosis type 1.

Heterozygous germ-line mutations in DNA mismatch repair (MMR) genes predispose individuals to hereditary nonpolyposis colorectal cancer (HNPCC), whereas with homozygous MMR gene mutations children are diagnosed at an early age with de novo neurofibromatosis type 1 (NF1) and/or hematological malignancies. Here, we describe a mutation, MLH1 P648S, which was found in a typical HNPCC family, with one homozygous child displaying mild features of NF1 and no hematological cancers. To evaluate the pathogenicity of the mutation, we studied both the expression and the function of the mutated protein.

Descending serotonergic facilitation mediated through rat spinal 5HT3 receptors is unaltered following carrageenan inflammation.

A descending facilitatory drive originating from superficial dorsal horn NK1-expressing neurones and relaying through parabrachial and rostroventral medial medulla to act on deep dorsal horn neurones, mediated through spinal 5HT3 receptors, was recently documented. To determine if this pathway plays a role in the pathophysiology of inflammation, we investigated the effects of spinally administered ondansetron (a selective 5HT3 receptor antagonist) on deep dorsal horn neuronal responses in carrageenan inflamed and naïve animals using in vivo electrophysiology. The mechanical and thermal evoked responses of spinal neurones were dose dependently attenuated by ondansetron to a similar degree in both groups.

Retargeted clostridial endopeptidases: inhibition of nociceptive neurotransmitter release in vitro, and antinociceptive activity in in vivo models of pain.

Clostridial neurotoxins potently and specifically inhibit neurotransmitter release in defined cell types. Previously reported data have demonstrated that the catalytically active LH(N) endopeptidase fragment of botulinum neurotoxin type A (termed LH(N)/A) can be retargeted to a range of cell types in vitro to lead to inhibition of secretion of a range of transmitters. Here, we report the synthesis of endopeptidase conjugates with in vitro selectivity for nociceptive afferents compared to spinal neurons.

Human brain wave activity during exposure to radiofrequency field emissions from mobile phones.

The aim of this study was to determine whether there is an effect of mobile phone electromagnetic field emissions on the human electroencephalograph (EEG). EEG recordings from ten awake subjects were taken during exposure to radiofrequency (RF) emissions from a mobile phone positioned behind the head. Two experimental trials were conducted.

Obstetric and gynecologic complications in women with Marfan syndrome.

Objective: To analyze the maternal and fetal outcomes of pregnancy and gynecologic problems in women with Marfan syndrome.

Study Design: The outcomes of 14 pregnancies in 4 women with Marfan syndrome were prospectively observed between January 1988 and December 2000. The cardiovascular and obstetric complications were analyzed.