Merkel cell carcinoma: report of seven cases

Merkel cell carcinoma (MCC) is an infrequent, highly malignant, primary skin tumor derived from neuroendocrine cells. Most MCCs occur in elderly individuals, on sun-exposed areas of the body, with the head and neck being the most common sites. We present 7 patients (2 male and 5 female, age 45-80 years) suffering from MCC and treated between 1993 and 2000. All tumors were located on the head and neck and varied from 0.9 to 2.3 cm in size. Five of the patients had stage II disease, 1 patient had stage Ia disease and 1 patient had stage III disease. Six of the patients had positive regional lymph nodes. All patients had local excision of the tumor. Six of them also had lymph node dissection and in 5 of them a superficial parotidectomy was performed. Five patients received adjuvant radiotherapy and 3 of them also received chemotherapy. Local and cervical lymph node recurrence was observed in only 1 patient. Metastases occurred in 5 patients. One patient died within 10 days for other reasons. The patient with the stage III tumor had a survival of 7 months. The other 5 patients had survivals varying from 15 to 54 months. MCC is a skin tumor with very poor prognosis and high recurrence and metastatic rates. Its treatment is still under discussion. Radical excision of the tumor is the main method of treatment. Selective lymph node dissection is suggested. Superficial parotidectomy seems necessary, especially if the tumor is on the auricle. Adjuvant radio- and chemotherapy may extend survival in case of small-size tumors.     

The problem of predicting food intake during the period of adaptation to a new food: a model

A model is described which aims to predict intake immediately following a change from one food to another that is higher in bulk content; it deals with the transition from one 'equilibrium' intake to another. The system considered is an immature pig fed ad libitum on a single homogeneous food, which is balanced for nutrients and contains no toxins so that the first limiting resource is always energy. It is assumed that an animal has a desired rate of food intake (DFI) which is that needed to meet the energy requirements for protein and lipid deposition and for maintenance. DFI may not be achieved if a bulk constraint to intake exists. Where a bulk constraint operates intake is calculated as constrained food intake (CFI) where (where WHC is the water-holding capacity of the food (kg water/kg dry food) and Cwhc is the animal's capacity for WHC (units/kg live weight per d)). Where intake is not constrained it is assumed that genetic potential will be achieved. Potential growth rate is described by the Gompertz growth function. Where intake is constrained, growth will be less than the potential. Constrained growth rate is predicted as where W is pig weight (kg), EI is energy intake (MJ/d), Em is the energy required for maintenance (MJ/d) and eg is the energy required for unit gain (MJ/kg). The value of eg depends on weight and the fattening characteristics of the pig. Actual growth is predicted to be the lesser of potential and constrained growth. To deal with adaptation it is assumed that the time taken to reach equilibrium depends on the difference in WHC values between the previous and current food and that the capacity to consume food bulk is related to the WHC of the current food. It is proposed that the capacity for WHC on the first day on a new food will be equal to the current capacity for WHC on the last day of the previous food. Thus where FI is food intake (kg/d). Thereafter Cwhc will gradually increase over time to a maximum of 0.27 g/kg. The rate of change in Cwhc is made to be the same for all pigs and all foods. The increase in capacity over time is assumed to be linear at the rate of 0.01 units/d. The model was tested using published data. Qualitatively the predictions of the model were in close agreement with the relevant observed data in at least some cases. It is concluded that the underlying theoretical assumptions of the model are reasonable. However, the model fails to predict initial intake when changed to foods high in wheat-bran content and fails to predict the intake of a non-limiting food where compensatory increases in intake and gain occur. The model could be adapted to overcome the first failure by taking into account the time course of digestive efficiency following a change in food. To deal with the second would require a sufficient understanding of the time course of compensatory growth.     

A cohort study on Helicobacter pylori serology before and after induction in the Hellenic Navy

BACKGROUND AND AIMS: To determine whether military personnel are at increased risk of Helicobacter pylori (HP) infection in proportion to their occupation during their national service in the armed forces. MATERIALS AND METHODS: Serum samples were obtained from 142 young male Hellenic Navy recruits (mean age, 23.6 years; range, 20-30 years). The first specimen was obtained during their induction into the Hellenic Navy, and the second was obtained after having served for 8 months in different services within Greece. An enzyme-linked immunosorbent assay was used to detect HP-specific immunoglobulin G antibodies. Statistical analysis was performed using the sign test, logistic regression, and the chi 2 test. RESULTS: The crude seropositivity rate increased from 19.01% to 28.16% (p = 0.007). Of the 115 initially seronegative subjects, 17 (14.8%) seroconverted. The most important predictive variable for seroconversion was deployment in a crowded commission (> 20 subjects) combined with the absence of air conditioning in personnel sleeping quarters (p = 0.03, odds ratio = 3.14). CONCLUSION: Our data suggest that the risk of HP infection increases among 20- to 30-year-old individuals during their national service. Degrading environmental conditions may play a major role in HP transmission between young adults who serve in the armed forces.     

Immunotherapy of advanced malignancy by direct gene transfer of an interleukin-2 DNA/DMRIE/DOPE lipid complex: phase I/II experience.

PURPOSE: We have completed a phase I study, followed by three phase I/II studies, in patients with metastatic melanoma, renal cell carcinoma (RCC), and sarcoma in order to evaluate the safety, toxicity, and antitumor activity of Leuvectin (Vical Inc, San Diego, CA), a gene transfer product containing a plasmid encoding human interleukin (IL)-2 formulated with the cationic lipid 1, 2-dimyristyloxypropyl-3-dimethyl-hydroxyethyl ammonium bromide/dioleyl-phosphatidyl-ethanolamine (DMRIE/DOPE) and administered intratumorally. PATIENTS AND METHODS: Twenty-four patients were treated in the phase I study. Leuvectin doses were 10 microg, 30 microg, or 300 microg weekly for 6 weeks. In three subsequent phase I/II studies, a total of 52 patients (18 with melanoma, 17 with RCC, and 17 with sarcoma) were treated with further escalating doses of Leuvectin: 300 microg twice a week for 3 weeks, 750 microg weekly for 6 weeks, and 1,500 microg weekly for 6 weeks. RESULTS: There were no drug-related grade 4 toxicities and only one grade 3 toxicity, but the majority of patients experienced mild constitutional symptoms after treatment. In the phase I/II studies, 45 patients were assessable for response (14 with RCC, 16 with melanoma, and 15 with sarcoma). Two patients with RCC and one with melanoma have achieved partial responses lasting from 16 to 19 months and continuing. In addition, two RCC, three melanoma, and six sarcoma patients had stable disease lasting from 3 to 18 months and continuing. The plasmid was detected by polymerase chain reaction assay in the posttreatment samples of 29 of 46 evaluated patients. Immunohistochemistry studies on serial biopsy specimens showed increased IL-2 expression and CD8(+) infiltration after treatment in the tumor samples of several patients (12 and 16, respectively). CONCLUSION: Direct intratumoral injection of Leuvectin is a safe and possibly effective immunotherapeutic approach in the treatment of certain tumor types.     

Intra-amniotic corticosteroids for preterm lung maturation in sheep

OBJECTIVE: The purpose of this study was to compare efficacy on fetal lung maturation of intra-amniotic betamethasone or budesonide with the efficacy of maternal intramuscular betamethasone. STUDY DESIGN: Pregnant ewes received intra-amniotic betamethasone (0.5 mg/kg or 2 mg/kg fetal weight), intra-amniotic budesonide (0.5 mg/kg or 2 mg/kg), maternal intramuscular betamethasone (0.5 mg/kg maternal weight), intra-amniotic saline solution, or maternal saline solution. Lambs were delivered 2 or 7 days later, at 124 days of gestation for measurement of respiratory system compliance, ventilatory efficiency index, and surfactant levels. RESULTS: Lung function increased 2 days after maternal betamethasone, intra-amniotic betamethasone (2 mg/kg), and intra-amniotic budesonide (2 mg/kg) administration and 7 days after maternal betamethasone or intra-amniotic budesonide (2.0 mg/kg) administration. Lung function was not improved 7 days after intra-amniotic betamethasone (2.0 mg/kg) administration or 2 days after intra-amniotic betamethasone (0.5 mg/kg) or intra-amniotic budesonide (0.5 mg/kg) administration. Intra-amniotic corticosteroid administration increased fetal death and respiratory morbidity. CONCLUSION: Intra-amniotic corticosteroid administration improved preterm lung function, but the associated morbidity and mortality rates suggest that they are not suitable for clinical use.     

High prevalence of decreased cortisol reserve in brain-dead potential organ donors

OBJECTIVE: To investigate the adrenocortical function in brain-dead patients, potential organ donors. DESIGN: Prospective study. SETTING: Intensive care units in two teaching hospitals. PATIENTS: A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 +/- 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. INTERVENTIONS: In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 microg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 microg/dL after the administration of adrenocorticotropic hormone were defined as responders. MEASUREMENTS AND MAIN RESULTS: After the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 +/- 6.2 vs. 17.0 +/- 6.6 microg/dL, p <.001) and stimulated (16.9 +/- 6.3 vs. 23.9 +/- 5.7 microg/dL, p =.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p <.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r =.71, p =.001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p =.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 +/- 11.4 vs. 6.8 +/- 4.2 microg/dL, p =.003) and stimulated serum cortisol (28.8 +/- 9.9 vs. 16.3 +/- 4.3 microg/dL, p =.008). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.     

Typing for HLA Class I Gene Products Using Plasma as Source

Soluble HLA class I proteins have been found in serum or plasma of healthy and diseased individuals. Here we present evidence that these molecules can be readily used for determination of the HLA type by biochemical methods. Immunoprecipitation of the soluble class I gene products using monomorphic monoclonal antibodies coated to immunobeads and one-dimensional isoelectric focusing followed by immunoblotting represents a feasible and reproducible technique for typing. Analysis of these gene products in families (n = 12, with a total of 62 individuals) as well as in the population (n = 82) showed that all serologically defined antigens tested to date were present in plasma. A reference chart established primarily for the membrane-bound antigens could also be used for the soluble ones.     

Impaired Glucose Metabolism and the Exaggerated Blood Pressure Response to Exercise Treadmill Testing in Normotensive Patients

The authors aimed to investigate the association between glucose metabolism measures and the exaggerated blood pressure response (EXBPR) to exercise testing in normotensive nondiabetic patients. One hundred and forty-two consecutive patients underwent office blood pressure (BP) measurements, 24-hour BP monitoring, echocardiography, and treadmill exercise test according to the Bruce protocol. The population was divided into 2 groups according to EXBPR at a submaximal workload level. Furthermore, blood samples were obtained for fasting glucose (FG), fasting insulin (FI), and lipid profile assessment. Measures of insulin resistance (homeostasis model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI], and McAuley index) were also estimated, and a standardized oral glucose tolerance test was performed to evaluate glucose levels at 120 minutes (G120). Patients with EXBPR (n=40; 27 men) compared with those without EXBPR (n=102; 66 men) were older by 4±6 years (P<.001). FG, FI, G120, HOMA-IR, QUICKI, and McAuley index differed in patients with EXBPR compared with those without EXBPR (P<.001 for all). Logistic multivariable regression models revealed that the studied glucose metabolism measures, duration of exercise, and 24-hour systolic BP remained determinants of EXBPR (P<.05 for all) after adjustment. Impaired glucose measures are significant determinants of EXBPR to exercise testing in normotensive nondiabetic patients, suggesting that impaired glucose metabolism may contribute to adverse cardiovascular prognosis including new-onset hypertension.