The Significance of Histology and Morphometry in Predicting Lymph Node Metastases in Patients with Squamous Cell Carcinoma of the Vulva

The material consists of a series of 73 patients with squamous cell carcinoma of the vulva. The site and the size of the primary tumor and the histological status of the lymph nodes of the groin were known. Two pathologists evaluated nuclear hyperchromatism, nuclear polymorphism, histological differentiation, number of mitoses, inflammatory response, and vascular invasion and graded these parameters from one to three. The reliability of the histopathological grades evaluated by the κ coefficient showed considerable interobserver variation. Despite this a model which included the subjective parameter nuclear hyperchromatism could predict patients without lymph node metastases. The model consisted of patients with tumors which were not situated on the clitoris, were less than 40 mm in diameter, and exhibited only slight hyperchromatism. The model fitted 19 (26%) and 14 (19%) of the patients with two different pathologists evaluating the nuclear hyperchromatism and none of these patients had lymph node metastases. The quantitative parameter—mean nuclear volume—determined by morphometry was of no diagnostic value for the prediction of patients without groin node metastases at the time of operation.     

The potential role of lonidamine (LND) in the treatment of malignant glioma

Summary Up-to-date unsatisfactory results obtained in multimodality treatments of malignant glioma have prompted the research of new therapeutic modalities with unconventional modes of action. Lonidamine (LND) is a drug which reduces aerobic glycolytic activity in both human and experimental tumors. This effect mainly depends on the inhibition of mitochondrially-bound hexokinase (HK) which is present in large amounts in malignant cells. A Phase II study was conducted on patients with recurrent glioma; 12 patients were admitted to the study. Clinical side effects were moderate, necessitating a reduction of the dosage in only 1 case. The objective results were evaluated according to the indications of Levin. 2 responders and 3 cases of stable disease were observed out of 10 evaluable patients. The potential value of this new drug is discussed.     

Recombination does not generate pinworm susceptibility during experimental crosses between two mouse subspecies

The susceptibility to Aspiculuris tetraptera of European Mus musculus hybrids is thought to reflect the disruption of genomic co-adaptation through recombination of the parental genomes. Here, we compared the susceptibility to this parasite between parents and experimental hybrids (intersubspecific until F4, intrasubspecific F1, F2) to clarify the contributions of heterosis and subspecies incompatibility. F1 showed hybrid vigor. Unlike intrasubspecific F2, intersubspecific F2 were less resistant than F1, but revealed no increased susceptibility relative to the parents. Intersubspecific F3 and F4 showed the same hybrid vigor as F1. Heterosis contributed most to the resistance, but the differences between intra- and intersubspecific F2 suggested genomic incompatibilities between subspecies. However, the susceptibility did not increase through the recombination process, showing that disruption of co-adaptation does not directly affect resistance. Even if previous studies still support the selective role of parasites in the current hybrid zone, an alternative hypothesis on the origin of hybrid susceptibility is warranted.     

Pain in individuals with RASopathies: Prevalence and clinical characterization in a sample of 80 affected patients

Pain in individuals with RASopathies is a neglected topic in literature. In this article, we assessed prevalence and profile of pain in a sample of 80 individuals affected by RASopathies. The study sample included individuals with Noonan syndrome (N = 42), Costello syndrome (N = 17), and cardio‐facio‐cutaneous syndrome (N = 21). A set of standardized questionnaires and scales were administered (VAS/numeric scale, r‐FLACC, Wang‐Baker scale, NPSI, BPI, NCCPC‐R) to detect and characterize acute and chronic pain and to study the influence of pain on quality of life (PEDs‐QL, SF‐36) and sleeping patterns (SDSC); revision of past medical history and multisystemic evaluation was provided. Available clinical data were correlated to the presence of pain. High prevalence of acute (44%) and chronic (61%) pain was documented in the examined sample. Due to age and intellectual disability, acute pain was localized in 18/35 individuals and chronic pain in 33/49. Muscle‐skeletal and abdominal pain was more frequently reported. The intensity of acute and chronic pain interfered with daily activities in 1/3 of the sample. Pain negatively impacted on QoL and sleeping patterns. This work documents that pain is highly prevalent in RASopathies. Future studies including subjective and objective measures of pain are required to discriminate a somatosensory abnormality from an abnormal elaboration of painful stimuli at a central level.     

A severe form of amyloidotic polyneuropathy in a Costa Rican family with a rare transthyretin mutation (Glu54Lys)

Four affected siblings in a Costa Rican family presented an aggressive polyneuropathy with widespread involvement of many visceral organs and onset during the third decade of life with rapid loss of muscle mass in the lower limbs and severe dysautonomy. The medical histories include vitreous opacity, cardiac enlargement, dermal and gastrointestinal infiltration, and autonomic dysfunction including circulatory compromise and gastrointestinal disturbances. Histological studies using Congo red stain and immunohistochemical assays with antibodies against the transthyretin (TTR) protein showed widespread deposition of amyloid in extracellular areas, including dermis and gastrointestinal lamina propia, endo- and perineural spaces, and vascular walls. A mutation search in the transthyretin (ttr) gene was performed seeking the cause of this severe form of familial amyloidotic polyneuropathy (FAP). We applied single-stranded conformational polymorphism (SSCP)-analyses followed by sequencing of the four exons of the ttr gene, revealing a point mutation in exon 3, a G to A transition that causes a Glu54Lys codon change. Western blots of plasma proteins incubated with anti-transthyretin antibodies after gel electrophoresis provided separation of wild-type and mutant TTR protein in affected family members.     

Metastatic Psammomatous Somatostatinoma of the Pancreas Causing Severe Ketoacidotic Diabetes Cured by Surgery

A case of somatostatin-producing pancreatic tumor associated with severe insulindependent diabetes mellitus and ketoacidotic coma is reported. The tumor, a 10-cm expansile mass arising from the pancreatic tail of a 70-yr-old woman, was first detected by ultrasonography, performed because of abdominal pain, and subsequently confirmed by computed tomography and fine-needle tumor aspiration. Pathologic investigation showed a predominatly solid-trabecular structure with scattered microacini and psammomatous bodies. A large proportion of tumor cells expressed somatostatin and/or calcitonin. Following resection of the primary tumor and three peripancreatic lymph nodes with metastases, the patient recovered rapidly from her diabetic syndrome and remained in substantially good health during a subsequent 8-yr follow-up period, without evidence of tumor recurrence.     

Effect of sulglycotide treatment on cell kinetics alterations induced by aspirin in humans

The effect on gastric epithelial cell proliferation of small doses of aspirin was evaluated in 9 healthy volunteers, with or without administration of sulglycotide, a sulfated glycopeptide with cytoprotective properties. Cell kinetics study was performed by incubation of gastric biopsies with bromodeoxyuridine (BrdU) and immunohistochemistry. A decrease of BrdU-labeling index and a shortening of the height of gastric columns were observed after treatment with aspirin and placebo. No variations were observed after treatment with aspirin and sulglycotide. A decrease of the epithelial cell renewal could be one of the damaging effects of aspirin on the gastric mucosa. The treatment with sulglycotide seems to be effective to prevent this alteration.     

Administration of ciprofibrate to lactating mothers induces PPARα-signaling pathway in the liver and kidney of suckling rats

It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats.     

No evidence for involvement of the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus in early onset obesity

In light of evidence of linkage of obesity to chromosome 2q31-q37, we hypothesized that the calpain-10 gene 'high-risk' haplotype combination for non-insulin-dependent diabetes mellitus (NIDDM) is involved in early onset obesity. We screened the NIDDM 'high-risk'-haplotype combination formed by the alleles 112 and 121 of the polymorphisms UCSNP-43, -19, and -63 in 166 families consisting of an extremely obese child or adolescent (mean BMI percentile: 99.3+/-1.38), one or more obese sibs (mean BMI percentile: 97.42+/-2.88), and both of their parents. Genotyping for three calpain-10 gene polymorphisms was performed by polymerase chain reaction (PCR) with (a) length polymorphism detection (UCSNP-19) or (b) allele-specific PCR (UCSNP-43 and -63). To allow for correct haplotype assignment all individuals were additionally genotyped for two microsatellite markers (D2S125 and D2S2338). We followed a hierarchical test procedure. As the first step, model-free linkage analysis was performed using maximum likelihood binomial statistics. The second stage consisted of a one-sided asymptotic pedigree disequilibrium test for the UCSNP-43 and on an exploratory level for the other SNP-markers and all haplotypes formed by the three SNPs. The final stage investigated the reported haplotype combination. We failed to detect an initial linkage of obesity to this region (LOD score <0.4). All subsequent exploratory analyses were negative. Our analysis of the relationship between the NIDDM 'high-risk' haplotype combination and extreme early onset obesity revealed no evidence for linkage and association.