Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Functional study on Boswellia phytosome as complementary intervention in asthmatic patients.

OBJECTIVE: The combination of inhaled corticosteroids (ICS) and long-acting beta-agonists (LABAs) is recommended for the treatment of patients with mild-to-severe persistent asthma. However, given the lack of definite and safe therapies, complementary or alternative medicines are frequently used by asthmatic patients in combination with standard treatments. PATIENTS AND METHODS: A group of asthmatic subjects have been enrolled in this multicenter study; after having verified the compliance to their current medical therapy (ICS + LABAs), the subjects have been randomized to receive Casperome® 500 mg/day or no additional treatment for a period of 4 weeks. They were also asked to keep track of the number of inhalations required per day and any adverse events through a daily form. RESULTS: A total of 32 subjects were enrolled in the study. Subjects receiving Casperome® 500 mg/day in addition to the standard ICS + LABAs treatment showed a decrease in the number of inhalations needed compared to patients who did not receive Casperome® therapy. The treatment was well tolerated and only mild-moderate adverse events were registered. CONCLUSIONS: The use of Casperome® 500 mg/day is beneficial for asthmatic patients as it helps reduce the need for inhalation therapy with ICS + LABA.

Role of immunoglobulins in neonatal sepsis.

Neonates, especially VLBW, are at high risk for sepsis related morbidity and mortality for immaturity of their immune system and invasive NICU practices. The paucity of immunoglobulins in preterm neonates consequently to the immaturity of immune system contributes to their high risk for systemic infection. The use of intravenous IgM enriched immunoglobulins, with higher antimicrobial activity than standard IgG, has been demonstrated in a retrospective study to reduce short term mortality in VLBW infant with proven sepsis. Larger, randomized prospective trials given the enormous burden of morbidity and mortality imposed by neonatal sepsis should urgently be addressed not only to validate this results but also to tailor the optimal scheme of treatment.

Is it worthwhile using a transcutaneous bilirubinometer in the nursery?

Jaundice is a potential threat to neonatal health and/or life. The advantages and limitations of transcutaneous determination of bilirubin concentration and current devices are briefly discussed in this paper.

Long-term follow-up of prostate cancer patients treated with vaccine and definitive radiation therapy.

BACKGROUND: Vaccine therapy in combination with radiation therapy may improve distant and/or local control in prostate cancer. We present long-term follow-up data on the secondary and exploratory endpoints of safety and biochemical failure, respectively, from patients with clinically localized prostate cancer treated definitively with a poxviral vector-based therapeutic vaccine combined with external beam radiation therapy (EBRT). METHODS: Thirty-six prostate cancer patients received definitive EBRT plus vaccine. A total of 18 patients were treated with adjuvant standard-dose interleukin-2 (S-IL-2) (4 MIU m(-2)) and 18 were treated with very low-dose IL-2 (M-IL-2) (0.6 MIU m(-2)). Seven patients were treated with EBRT alone. Twenty-six patients treated with EBRT plus vaccine returned for follow-up, and we reviewed the most recent labs and clinical notes of the remaining patients. RESULTS: Median follow-up for the S-IL-2, M-IL-2 and EBRT-alone groups was 98, 76 and 79 months, respectively. Actuarial 5-year PSA failure-free probability was 78%, 82% and 86% (P=0.58 overall), respectively. There were no significant differences between the actuarial overall survival and the prostate cancer-specific survival between the two vaccine arms. Of the 26 patients who returned for follow-up, Radiation Therapy Oncology Group grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicity was seen in 19% and 8%, respectively, with no difference between the arms (P=1.00 and P=0.48 for grade ≥2 GU and GI toxicity, respectively). In all, 12 patients were evaluated for PSA-specific immune responses, and 1 demonstrated a response 66 months post-enrollment. CONCLUSIONS: We demonstrate that vaccine combined with EBRT does not appear to have significant differences with regard to PSA control or late-term toxicity compared with standard treatment. We also found limited evidence of long-term immune response following vaccine therapy.

Neuroprotective efficacy of caramiphen against soman and mechanisms of its action.

BACKGROUND AND PURPOSE: Caramiphen is a muscarinic antagonist with potent anticonvulsant properties. Here, we investigated the efficacy of caramiphen against behavioural seizures and neuropathology induced by the nerve agent soman, and revealed two mechanisms that may underlie the anticonvulsant efficacy of caramiphen. EXPERIMENTAL APPROACH: Rats were given caramiphen at 30 or 60 min after treatment with soman. Neuronal loss in the basolateral amygdala (BLA) and neuronal degeneration in the amygdala, hippocampus, piriform cortex, entorhinal cortex and neocortex, were investigated 24 h after soman, using design-based stereology and FluoroJade-C staining. The effects of caramiphen on NMDA-, AMPA- and GABA-evoked currents were studied in the BLA region of in vitro brain slices from un-treated rats, using whole-cell recordings. KEY RESULTS: Caramiphen given either 30 min or 60 min after soman, suppressed behavioural seizures within 10 min, but required 1∼4.5 h for complete cessation of seizures. Neuronal loss and degeneration were significantly reduced in the caramiphen-treated, soman-exposed rats. Postsynaptic currents evoked by puff-application of NMDA on BLA principal cells were reduced by caramiphen in a dose-dependent manner (100 µM, 300 µM and 1 mM), while GABA-evoked currents were facilitated by 100 µM and 300 µM, but depressed by 1 mM caramiphen. AMPA-evoked currents were not affected by caramiphen. CONCLUSIONS AND IMPLICATIONS: Caramiphen offered partial protection against soman-induced seizures and neuropathology, even when given 60 min after soman. NMDA receptor antagonism and facilitation of GABAergic inhibition in the BLA may play a key role in the anticonvulsive and neuroprotective properties of caramiphen.

Mechanics of biting in great white and sandtiger sharks.

Although a strong correlation between jaw mechanics and prey selection has been demonstrated in bony fishes (Osteichthyes), how jaw mechanics influence feeding performance in cartilaginous fishes (Chondrichthyes) remains unknown. Hence, tooth shape has been regarded as a primary predictor of feeding behavior in sharks. Here we apply Finite Element Analysis (FEA) to examine form and function in the jaws of two threatened shark species, the great white (Carcharodon carcharias) and the sandtiger (Carcharias taurus). These species possess characteristic tooth shapes believed to reflect dietary preferences. We show that the jaws of sandtigers and great whites are adapted for rapid closure and generation of maximum bite force, respectively, and that these functional differences are consistent with diet and dentition. Our results suggest that in both taxa, insertion of jaw adductor muscles on a central tendon functions to straighten and sustain muscle fibers to nearly orthogonal insertion angles as the mouth opens. We argue that this jaw muscle arrangement allows high bite forces to be maintained across a wider range of gape angles than observed in mammalian models. Finally, our data suggest that the jaws of sub-adult great whites are mechanically vulnerable when handling large prey. In addition to ontogenetic changes in dentition, further mineralization of the jaws may be required to effectively feed on marine mammals. Our study is the first comparative FEA of the jaws for any fish species. Results highlight the potential of FEA for testing previously intractable questions regarding feeding mechanisms in sharks and other vertebrates.

Outcome and toxicity associated with a dose-intensified, maintenance-free CHOP-based chemotherapy protocol in canine lymphoma: 130 cases.

A dose-intensified/dose-dense chemotherapy protocol for canine lymphoma was designed and implemented at the Veterinary Hospital of the University of Pennsylvania. In this study, we describe the clinical characteristics, prognostic factors, efficacy and toxicity in 130 dogs treated with this protocol. The majority of the dogs had advanced stage disease (63.1% stage V) and sub-stage b (58.5%). The median time to progression (TTP) and lymphoma-specific survival were 219 and 323 days, respectively. These results are similar to previous less dose-intense protocols. Sub-stage was a significant negative prognostic factor for survival. The incidence of toxicity was high; 53.9 and 45% of the dogs needed dose reductions and treatment delays, respectively. Dogs that required dose reductions and treatment delays had significantly longer TTP and lymphoma-specific survival times. These results suggest that dose density is important, but likely relative, and needs to be adjusted according to the individual patient's toxicity for optimal outcome.

Radio hyperthermia for re-treatment of superficial tumours.

PURPOSE: Relapse remains an unsolved problem for previously radio-treated patients. Our purpose is to evaluate the role of radio-hyperthermia (RT-HT) in the retreatment of superficial recurrences. MATERIALS AND METHODS: From 1998 to 2007, 51 patients affected by four histological types (breast recurrences (group A), melanoma recurrences (group B), head and neck recurrences (group C), and others (group D)) of 76 superficial lesions, were enrolled at Mauriziano Hospital at the Research Institute of Cancer Care Candiolo (IRCC) in Turin. All patients had previously undergone RT except 6 patients of group B. The total mean retreatment dose was 31.8 Gy (20-60 Gy), while the mean of HT sessions was 5 (1 to 8), temperature ranged from 38.5 degrees C (T min) to 44 degrees C (T max). RESULTS: Acute cutaneous toxicity was 77.6% G1, 22.4% G2, none for G3. Forty-five days later we observed: for group A 65.9% complete response (CR), 29.5% partial response (PR), 4.5% non-response (NR); for group B 33.3% CR, 25% PR and 41.7% NR; for group C 40% CR, 13.3% PR, 46.7% NR, for group D 60% CR and 40% NR. 18 months later group A presented 72.7% local control (LC), 20.5% stable disease (SD) and 6.8% non-control (NC), group B 50% LC, 16,7% SD and 33.3% NC, group C 33.3% LC, 40% SD and 26.7% NC, group D 40% LC and 60% NC. Early response, size of lesions < or =3 cm, T max > or =42 degrees C and RT doses > or =40 Gy were predictive outcome factors. CONCLUSIONS: We confirmed that radio-hyperthermia is useful in re-irradiation with a very high patient compliance.

Infiltrating giant cell tumor in a case of Paget's disease of bone.

Giant cell tumor (GCT) of the bone, also called osteoclastoma, is a rare complication of Paget's bone disease. We report a patient from Southern Italy who developed a GCT infiltrating the neighboring tissues. The natural history and the therapeutic outcomes of this unique complication of Paget's bone disease are presented.

Survival and long-term neurodevelopmental outcome of extremely premature infants born at 23-26 weeks' gestational age at a tertiary center.

OBJECTIVE: Long-term outcome, including school-age function, has been infrequently reported in infants born at ages as young as 23-26 weeks' gestation. The objective of this study is to report outcome on a large cohort of these infants to understand better the risks and factors that affect survival and long-term prognosis. METHODS: Records from 1036 infants who were born between January 1, 1986, and December 31, 2000, were analyzed retrospectively by logistic regression to correlate multiple factors with both survival and long-term outcome. A total of 675 surviving infants were analyzed at a mean age of 47.5 months for developmental outcome. A subset of 147 surviving infants who were born before 1991 were followed through school-age years using the University of Vermont Achenbach Child Behavioral Checklist and Teachers Report Form. Longitudinal follow-up was performed comparing 1-year outcome with school-age performance. RESULTS: Gestational age and recent year of birth correlated highly with survival. Maternal nonwhite race, female sex, inborn status, surfactant therapy, single gestation, and secondary sepsis also correlated positively with survival. Normal cranial ultrasound results, absence of chronic lung disease, female sex, cesarean delivery, and increased birth weight correlated favorably with long-term outcome. Infants who were born at 23 weeks were more likely to have severe impairments compared with those who were born at 24-26 weeks. Early follow-up identified most subsequent physical impairments but correlated poorly with school-age function. CONCLUSIONS: Survival continues to improve for infants who are born at extremely early gestational ages, but long-term developmental concerns continue to be prevalent. Early outcomes do not reliably predict school-age performance. Strategies that reduce severe intraventricular hemorrhage and chronic lung disease will likely yield the best chances to improve long-term outlook.

Neurodevelopmental follow-up at 36 months' corrected age of preterm infants treated with prophylactic indomethacin.

BACKGROUND: Previous reports have suggested that prophylactic indomethacin decreases cerebral blood flow and may play a role in the development of ischemic brain injury and developmental handicaps. OBJECTIVE: To assess the neurodevelopmental outcome of subjects at 36 months' corrected age (CA) who, as low-birth-weight infants, received prophylactic low-dose indomethacin within the first 24 hours of life to prevent patent ductus arteriosus. SETTING: Newborn intensive care nursery and outpatient follow-up clinic at Children's Hospitals and Clinics of Minneapolis, Minneapolis, Minn. DESIGN: Ninety infants with birth weights of 600 to 1250 g were entered into a prospective, randomized, controlled trial to receive either prophylactic indomethacin, 0.1 mg/kg, or placebo in the first 24 hours and again every 24 hours for 6 doses to prevent patent ductus arteriosus. Nonresponders were treated with standard therapeutic indomethacin or ligation. Neurodevelopmental assessment at approximately 36 months' CA included medical and developmental histories, physical examinations, and developmental testing using the Bayley II Scales of Infant Development on subjects up to 42 months' CA. Subjects were classified as (1) normal, (2) mildly to moderately abnormal, or (3) severely impaired. RESULTS: Forty-two (98%) of 43 subjects who received prophylactic indomethacin survived compared with 46 (98%) of 47 who received placebo. Sixty-six (75%) of 88 survivors were seen for neurodevelopmental assessment at 36 months' CA. This group included 29 (69%) of 42 who received prophylactic indomethacin and 37 (80%) of 46 who received placebo. Twenty-three (79%) of 29 infants in the prophylactic indomethacin group had normal neurodevelopmental assessments at 36 months' CA compared with 26 (70%) of 37 placebo-treated subjects (P = .68). Of 4 significantly impaired subjects treated with prophylactic indomethacin, 1 had spastic diplegia; 1, spastic quadriplegia; 1, cognitive delay; and 1, significant motor delay. Of 8 significantly impaired placebo-treated subjects, 7 had spastic diplegia; 1, microcephaly. CONCLUSION: The use of prophylactic low-dose indomethacin when initiated in the first 24 hours of life in low-birth-weight infants to prevent patent ductus arteriosus is not associated with adverse neurodevelopmental outcome at 36 months' CA.

Cryopreservation of single human spermatozoa.

A procedure is described that allows cryopreservation and efficient post-thaw recovery of either a single or a small group of human spermatozoa. This is achieved by injecting them into cell-free human, mouse or hamster zonae pellucidae before the addition of cryoprotectant. The method involves a combination of physical micromanipulation procedures and glycerol-mediated cryoprotection. Zonae were tracked by positioning them in straws between two small air bubbles prior to freezing. Spermatozoa from poor specimens were cryopreserved and their fertilizing ability after thawing was compared with that of fresh spermatozoa from fertile men. Human eggs used for fertilization testing were either 1 day old or in-vitro matured. Only 2% of the frozen zonae were lost and >75% of spermatozoa cryopreserved in this manner were recovered and prepared for intracytoplasmic sperm injection. The feasibility of cryopreserving a single spermatozoon was assessed. Fifteen motile spermatozoa were frozen in 15 zonae, of which 14 were recovered after thawing. Ten were injected into spare eggs, of which eight became fertilized. Spermatozoa recovered mechanically from human zonae fertilized the same proportion of oocytes as fresh fertile control spermatozoa. The recovery and fertilization rates with spermatozoa frozen in animal zonae were 87 and 78% respectively. The fertilization rate was marginally higher (P < 0.05) than that for spermatozoa frozen in human zonae, perhaps because the latter may have acrosome reacted more frequently. The zona pellucida appears to be an ideally suited sterile vehicle for storage of single spermatozoa.

Beneficial aspects of co-culture with assisted hatching when applied to multiple-failure in-vitro fertilization patients.

A study was conducted on patients who had attempted and failed previous in-vitro fertilization (IVF) procedures an average of 3.8 times following the application of assisted hatching with conventional culture systems. The aim of this investigation was to determine if addition of co-culture methodologies could reduce embryonic abnormalities and thus improve the prognosis for pregnancy. The study population consisted of 123 patients, subdivided into three patient categories. Previous IVF results from conventional culture were used to evaluate any potential benefits derived from the present co-culture application. Following co-culture, the rate of blastomere development was increased and the rate of fragmentation decreased. An increased rate of blastomere development was most noticeable in the patients aged < or = 39 years with no male factor as well as the intracytoplasmic sperm injection (ICSI) subgroup. Similarly, the rate of fragmentation was significantly reduced in the aforementioned subgroups. The most pronounced impact of co-culture was on pregnancy and implantation rates. The overall clinical and ongoing pregnancy rates were 38% (47/123) and 36% (44/123) respectively. The corresponding implantation rate was 17% (72/ 412) as shown by embryonic cardiac activity. The ongoing pregnancy rates in the < or = 39 years no male factor, > or = 40 years no male factor and ICSI no age limit patient subgroups were 41% (21/51), 30% (8/27) and 33% (15/45) respectively. The results indicate that addition of co-culture to the IVF procedure for poor-prognosis patients may be advisable.

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room.

OBJECTIVE: To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN: Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS: Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION: The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Reduced human lymphocyte blastogenesis and enhancement of adenosine triphosphate (ATP) by L-carnitine.

Carnitine is associated with lipid synthesis and its deficiency may lead to cardiomegaly with parenchymal lipid in the heart, kidney and liver. In our study we found that pretreatment of peripheral blood mononuclear cells (PBMC) with serial dilutions of L-Carnitine (100 micrograms/ml-1 pg/ml) inhibits, in a dose-dependent manner, lymphocyte DNA synthesis stimulated with PHA (20 micrograms/ml). L-Carnitine did not have any effect on resting PBMC. The maximum inhibition was found at 10 micrograms/ml of L-Carnitine. Moreover, in a time-course study and using an enzymatic analysis (ATP monitoring reagent), L-Carnitine enhanced ATP production on PBMC treated and untreated with PHA, reaching a maximum effect at 30 min incubation. In another set of experiments PBMC were treated with L-Carnitine alone and in combination with PHA, and the percent of receptors CD3, CD4, and CD8 were calculated with flow cytometry. After the cell incubation with L-Carnitine, the percent of all receptors studied did not change compared to L-Carnitine-untreated cells (controls). These data suggest that L-Carnitine inhibits, in a dose-dependent manner, lymphocyte blastogenesis induced by PHA, probably through the enhancement of ATP synthesis, which is considered an inhibitor of phospholipase C activity and a suppressor in lymphocyte cultures.

Effects of surfactant therapy on outcome of extremely premature infants.

Limits of viability of extremely premature infants have recently been addressed both in Europe and the United States. These reports, which demonstrate frequent adverse outcome of infants born before 26 weeks of gestation, have not considered the impact of surfactant therapy. We reviewed records of 445 infants born between 23 and 36 weeks gestation who were admitted to our nursery following the availability of surfactant treatment in 1986 through 1992. Two hundred and eighty-five infants were treated with surfactant (Survanta, Ross Laboratories) as part of controlled, prospective trials or as routine treatment under Food and Drug Administration approval. One hundred and fifty-six infants were unable to be treated with surfactant, as either they received placebo therapy during prospective trials or were born prior to approval of routine surfactant use in the United States. Four additional infants born following the commercial availability of surfactant did not receive surfactant therapy. Survival of untreated infants was 56% compared to 75% in treated infants (P < 0.001). Infants born at all gestational ages between 23 and 26 weeks had an increased likelihood of survival as a result of surfactant treatment. No differences in neurologic outcome between surfactant treated and non-treated infants were demonstrated at subsequent follow-up. We conclude that survival of extremely premature infants is improved following surfactant therapy and that subsequent neurologic outcome is not compromised as a result of this therapy.

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: effects of surfactant therapy.

Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors.