Cytogenetic biodosimetry and dose-rate effect after radioiodine therapy for thyroid cancer

This study set out to investigate chromosomal damage in peripheral blood lymphocytes of thyroid cancer patients receiving ¹³¹I for thyroid remnant ablation or treatment of metastatic disease. The observed chromosomal damage was further converted to the estimates of whole-body dose to project the adverse side effects. Chromosomal aberration analysis was performed in 24 patients treated for the first time or after multiple courses. Blood samples were collected before treatment and 3 or 4 days after administration of 2–4 GBq of ¹³¹I. Both conventional cytogenetic and chromosome 2, 4 and 12 painting assays were used. To account for dose-rate effect, a dose-protraction factor was applied to calculate the whole-body dose. The mean dose was 0.62 Gy (95% CI: 0.44–0.77 Gy) in the subgroup of patients treated one time and 0.67 Gy (95% CI: 0.03–1.00 Gy) in re-treated patients. These dose estimates are about 1.7-fold higher than those disregarding the effect of exposure duration. In re-treated patients, the neglected dose-rate effect can result in underestimation of the cumulative whole-body dose by the factor ranging from 2.6 to 6.8. Elevated frequency of chromosomal aberrations observed in re-treated patients before radioiodine therapy allows estimation of a cumulative dose received from all previous treatments.     

Free-flap mandibular reconstruction: a 10-year follow-up study

Free-flap reconstruction of oncologic mandibular defects has become the modern standard of care. However, no previous studies have established the long-term results of such reconstructions. The objective of this study was to review functional and aesthetic outcomes in patients a decade after free-flap mandibular reconstruction.A single surgeon's experience with free-flap reconstruction of the mandible was retrospectively reviewed. Eighty-two consecutive patients who underwent reconstruction from January of 1987 to December of 1990 were identified. Of the 34 patients still alive, 20 agreed to participate (response rate, 59 percent). To assess complications and functional outcome, patients were interviewed using validated questions and questions developed specifically for the study. Aesthetic outcome was judged by two independent observers. Panorex radiographs were obtained to assess bone resorption. Bone height was measured at standardized locations on the body, ramus, and symphysis and compared with the immediate postoperative Panorex radiographs. Differences in Panorex magnification were adjusted for by comparison of miniplate measurements. Mean length of follow-up was 11 years. Mean patient age at the time of the study was 48 years. Nineteen of 20 patients had malignant disease, one of whom had a local recurrence during the follow-up period. Two patients received radiation therapy preoperatively and 13 postoperatively. Mean length of mandible resection was 13 cm. Defect types were as follows (Jewer's classification): 12 L, 4 H, 3 LC, and 1 LCL. All flaps survived.At 10-year follow-up, aesthetic outcome was judged to be excellent in 55 percent of patients, good in 20 percent, fair in 15 percent, and poor in 10 percent. The aesthetic results were remarkably stable over time. Slight accentuation of subtle postoperative asymmetry became evident as facial aging progressed. Dental rehabilitation in the study group included five patients with osteointegrated implants and seven with conventional dentures. Seventy percent of patients reported a regular diet. The remainder required a soft diet. Food tolerance was good, as rated by the List Scale (mean score, 77 percent). Seventeen patients had easily intelligible speech, whereas three were intelligible with effort. At the midbody of the mandible, 92 percent of the postoperative bone height was preserved; at the midramus, 93 percent was maintained; and at the symphysis, 92 percent remained. In several patients, there was greater age-related bone loss from the residual native mandible compared with the reconstructed site. One patient developed an orocutaneous fistula following postoperative radiation therapy. Nine patients had miniplates removed, either because of plate problems or to allow implant placement. There were no cases of osteoradionecrosis, bone fracture, or miniplate fracture. There was no significant long-term disability related to the donor site.Free-flap reconstruction of the mandible provides excellent functional and aesthetic results that remain stable over time. Bone resorption is surprisingly minimal, even in the face of postoperative radiation therapy. The majority of patients are able to tolerate a regular diet and to either wear dentures or acquire osteointegrated implants. Acceptable speech and appearance are restored and continue to be a source of patient satisfaction at least a decade after surgery.     

Fluctuations of epstein-barr virus serological antibodies and risk for nasopharyngeal carcinoma: a prospective screening study with a 20-year follow-up

Background

The impact of variation of Epstein-Barr virus (EBV) antibody titers before the development of nasopharyngeal carcinoma (NPC) is still unclear. We analyzed the fluctuations of antibodies against EBV before histopathological diagnosis to assess the risk of NPC and aimed to provide a reliable basis for screening in high risk populations.

Methods

This study was based on a population-based screening program in Sihui County in Guangdong Province of China. A total of 18,986 subjects were recruited in 1987 and 1992, respectively. Baseline and repeated serological tests were performed for IgA antibodies against EBV capsid antigen (VCA/IgA) and early antigen (EA/IgA). Follow-up until the end of 2007 was accomplished through linkage with population and health registers. Cox proportional hazards regression model was used to estimate the relative risk of NPC in association with EBV antibodies. Time-dependent receiver operating characteristic curve (ROC) analysis was used to further evaluate the predictive ability.

Results

A total of 125 NPCs occurred during an average of 16.9 years of follow-up. Using baseline information alone or together with repeated measurements, serological levels of VCA/IgA and EA/IgA were significantly associated with increased risks for NPC, with a striking dose-response relationship and most prominent during the first 5 years of follow-up. Considering the fluctuant types of serological titers observed during the first three tests, relative risk was highest among participants with ascending titers of EBV VCA/IgA antibodies with an adjusted hazard ratio (HR) of 21.3 (95% confidence interval [CI] 7.1 to 64.1), and lowest for those with decreasing titers (HR = 1.5, 95% CI 0.2 to 11.4), during the first 5 years of follow-up. Time-dependent ROC analysis showed that VCA/IgA had better predictive performance for NPC incidence than EA/IgA.

Conclusion

Our study documents that elevated EBV antibodies, particularly with ascending titers, are strongly associated with an increased risk for NPC.     

Cytogenetic study of 20 cases of refractory anemia

The myelodysplastic syndromes are a group of hematological disorders not yet clearly defined. The authors describe the chromosomal aspects of 20 cases observed in the region of Clermont-Ferrand in comparison with the bibliographical data.     

Behavioral treatment of irritable bowel syndrome: a 1-year follow-up study

Sixteen clients afflicted with irritable bowel syndrome (IBS) were reassessed 1 year following completion of a multicomponent treatment package incorporating progressive muscle relaxation, thermal biofeedback, cognitive therapy, and IBS education. For the 14 patients who kept a 2-week symptom diary, significant reductions in ratings of abdominal pain and tenderness, diarrhea, and flatulence were obtained comparing pretreatment and follow-up symptom-diary ratings. Eleven of 14 clients were improved over pretreatment levels, 57% met the criteria for clinical improvement of at least a 50% reduction in major symptom scores, and all but 1 of 16 rated themselves as subjectively improved.     

Primary repair of the unilateral cleft lip nose in the Oriental: a 20-year follow-up

The unilateral cleft lip nasal deformity is corrected as a primary procedure with the lip repair. The abnormal attachment of the alar base is first released by an incision along the superior buccal sulcus and piriform margin. There is no intercartilaginous incision. Basically, we use the Brown-McDowell technique with the addition of an alar rim incision. Undermining of the ala between the two incisions is carefully and adequately done, splitting it into two layers. The first is a skin and the second, a chondrocutaneous (vestibular skin) layer, which is handled as a single unit, thus enhancing its vascularity. This second layer is a bipedicle flap with a broad medial pedicle and a narrow lateral pedicle at the alar base. When the alar base is rolled into its normal position, the chondrocutaneous unit hinging on its two pedicles counterrotates, correcting the subluxation of the ala, a major component of the cleft lip nasal deformity. We depend on the normal position of the alar base, the postoperative scar tissue, and the inherently thick nostril wall in the Oriental to keep the alar dome up. No transfixion sutures are used. Ten consecutive patients are shown 20 years after surgery. All had one operation only. None showed any disturbance of nasal growth.     

Radial fracture as an indicator of osteoporosis: a 10-year follow-up study

Of 136 patients studied at an average of 10.6 years after a distal radial fracture, 37.6% of the 109 women and 7.4% of the 27 men suffered a subsequent fracture. “Osteoporosis-related” fractures accounted for the majority of subsequent fractures sustained by the women. The prognostic significance of distal radial fracture in the adult female is discussed.     

ErbB-receptors expression and survival in breast carcinoma: a 15-year follow-up study

Aberrant expression of the epidermal growth factor receptor family has been implicated in the pathogenesis and progression of breast cancer and associated with poor prognosis. To evaluate the prognostic impact of the ErbB receptors expression profile, we analyzed a well-characterized series of 145 primary breast carcinomas for the simultaneous expression of epidermal growth factor receptor (EGFR/HER-1), ErbB-2 (HER-2), ErbB-3 (HER-3), and ErbB-4 (HER-4), using immunohistochemistry. Tumors were considered negative or positive for each marker when less than or more than 25% of the cancer cells were immunopositive. Expression of EGFR, ErbB-2, ErbB-3, and ErbB-4 was observed in 31 (21.4%), 65 (44.8%), 72 (49.7%), and 81 (55.9%) of the cases, respectively. There were significant associations between EGFR expression and pT status (P = 0.01), and between ErbB-3 expression and pN (P = 0.003), menopausal (P = 0.01) and PR (P < 0.001) status. The majority of the cases co-expressed two or more receptors. ErbB-3 resulted positive in 51/81 (63.0%) of the ErbB-4 positive cases and ErbB-3/ErbB-4 co-expression was statistically significant (P = 0.0003). As expected, ErbB-2 expression was associated with reduced overall survival at 15 years of follow-up (P = 0.04), even after adjusting for a series of other prognostic factors (P = 0.05). Moreover, cumulative analysis of ErbB-2/3/4 expression showed a strong positive association between higher total ErbB-2/3/4 expression score and worse prognosis (P = 0.002). The simultaneous expression in cancer cells of more than one ErbB receptor identifies a subset of breast cancer patients at high risk for poor survival.     

Ablative radioiodine therapy for hyperthyroidism: long term follow up study.

A total of 225 patients were treated for hyperthyroidism with 555 MBq (15 mCi) radioiodine to ablate the thyroid and induce early hypothyroidism. The efficacy of this treatment in eradicating hyperthyroidism and problems of follow up were assessed one to six years later from case records and questionnaires. Information was received from 197 out of 219 live patients (90%) and from 160 doctors concerning 207 patients (92%). Only three patients were not traced and six had died since treatment. The modal time to hypothyroidism was three months, and 64% of patients were hypothyroid at one year; 5.6% had failed to become euthyroid within one year. Ninety five per cent of patients had been seen by the doctor and 82% had had a thyroid test done within the past two years. Most doctors preferred patients to be returned to their care once thyroxine treatment was stabilised. An ablative dose of 131I is recommended as an effective means of treatment which has clear advantages over conventional methods. Good communications and effective follow up should ensure success.     

Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study

Apolipoprotein E (apoE) polymorphism is a genetic determinant of plasma lipid levels and of coronary heart disease (CHD) risk. We determined the apoE phenotypes and plasma lipid levels in 1577 youths aged 3 to 18 years in 1980. The subjects were randomly selected from five areas of Finland. ApoE phenotyping was performed directly from plasma by isoelectric focusing and immunoblotting. The apoE allele frequencies in the population sample were epsilon 2 = 0.039, epsilon 3 = 0.767, and epsilon 4 = 0.194. There were no differences in the apoE phenotype distribution between East and West Finland or between sexes. The concentrations of serum total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B increased with apoE phenotype in the order of E2/2, E3/2, E4/2, E3/3, E4/3, and E4/4. This increase was already seen in 3-year-old children; it was observed in both sexes, but was clearer in males than in females. The mean levels of high density lipoprotein (HDL) cholesterol, apolipoprotein A-I, triglyceride, Lp[a] lipoprotein, and the activity of lecithin:cholesterol acyltransferase did not differ between the apoE phenotypes. The observed differences in serum cholesterol remained fairly stable during the 6-year follow-up from 1980 to 1986, while the mean serum cholesterol concentration in the whole study population decreased by 6.3%. This study confirms the reported higher frequency of the epsilon 4 allele in Finns as compared to most other populations; this may contribute to the high rates of CHD in Finland as compared to most other populations. The results do not, however, explain the higher rate of CHD in East Finland in comparison to the western part of the country.     

Serum ghrelin and prediction of metabolic parameters in over 20-year follow-up

Ghrelin is a peptide hormone from the stomach, with an ability to release growth-hormone from the pituitary. Numerous cross-sectional studies indicate that ghrelin also has a role in metabolic abnormalities, such as metabolic syndrome and type 2 diabetes, but evidence for long-term effect is scarce. We investigated, whether ghrelin concentration measured in middle age would predict the development or absence of metabolic disturbances subsequently. Study population consisted of 600 middle-aged persons, and the follow-up time was approximately 21 years. Plasma total ghrelin concentration was measured at the baseline, and divided to tertiles. Numerous anthropometric and other clinical measurements (including blood pressure), and laboratory test were made both at the baseline and at the follow-up. After the follow-up the prevalence of high systolic blood pressure according to MetS IDF-criteria was the lowest in the highest ghrelin tertile, and the highest in the first (p < 0.03). When only subjects free of hypertension medication at baseline were considered, subjects belonging to the highest ghrelin tertile developed less new hypertension and high blood pressure according to IDF-criteria as well as medication for it during the follow-up (p < 0.05). Although serum insulin levels were negatively correlated to ghrelin levels at both points in time (p < 0.001 at baseline and p = 0.003 at follow-up), plasma ghrelin concentration did not predict the development of abnormalities in glucose tolerance. The association with ghrelin and metabolic syndrome was lost during the follow-up. In conclusion, our results suggest high ghrelin to be protective against the development of hypertension in the long-term follow-up.     

Long-term effects of growth hormone therapy on bone mineral density,body composition,and serum lipid levels in growth hormone deficient children: a 6-year follow-up study

AIM: To study the effects of growth hormone (GH) deficiency (GHD) and GH replacement therapy (GHRx) on bone mineral density (BMD) and body composition. METHODS: 59 GHD children participated (age range 0.4-16.9 years); the follow-up period was 6 years. Lumbar spine BMD (BMD(LS)), total-body BMD (BMD(TB)), and body composition were measured prospectively using dual-energy X-ray absorptiometry. RESULTS: Mean BMD(LS )and BMD(TB) were significantly reduced at the time of the diagnosis. The bone mineral apparent density of the lumbar spine (BMAD(LS)) was reduced to a lesser degree. The BMAD(LS) increased to normal values after 1 year; BMD(LS) and BMD(TB) normalized 1 year later. At the time of the diagnosis, the lean body mass was reduced and steadily increased during GHRx. Percentage of body fat was increased at baseline and normalized within 6 months. The severity of GHD was not associated with the BMD at diagnosis or the response to GHRx. CONCLUSION: Areal BMD(LS) and BMD(TB) and, to a lesser extent, BMAD(LS) are decreased in GHD children, but normalize within 1-2 years.