Stroke volume-directed administration of hydroxyethyl starch or Ringer's acetate in sitting position during craniotomy.

BACKGROUND: To determine the volumes required for stable haemodynamics and possible effects on the coagulation, we studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a sitting position. METHODS: Thirty craniotomy patients were randomised to receive either HES or RAC. Before positioning, SV, measured by arterial pressure waveform analysis, was maximised by boluses of fluid until SV did not increase more than 10%. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during surgery. RESULTS: Comparable haemodynamics were achieved with the mean [standard deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P = 0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95% confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss differed between the groups. CONCLUSION: Fluid filling with HES boluses resulted in a positive response in CI and SVI during the sitting position. The 34% smaller volume of HES than crystalloid and less positive fluid balance in the HES group might be important in craniotomy patients with decreased brain compliance.

Molecular characterization of Pegarn: a Drosophila homolog of UNC-51 kinase.

We have isolated and characterized the gene encoding a Drosophila melanogaster homolog of Caenorhabditis elegans UNC-51 (uncoordinated movement-51): Pegarn. Developmental Northern blot shows the Pegarn gene is expressed at all stages of development. The protein is detected throughout the Drosophila third instar larval central nervous system (CNS) in axons projecting out from the ventral ganglion and in the optic anlagen of the optic lobe. Heterozygous Pegarn mutant embryos show defects in larval axonal neuronal patterning, but survive to adulthood. Homozygous mutants have an even more deformed pattern of neuronal development and do not survive through the larval stages. The data from this research suggest the critical roles of Pegarn in CNS and PNS axonal formation in Drosophila melanogaster and indicates its similar role in other multicellular species.

Cancer incidence after radiotherapy for skin hemangioma: a retrospective cohort study in Sweden.

The cancer incidence was studied in 18,030 patients (33% males, 67% females) with skin hemangioma who were admitted to Radiumhemmet, Karolinska Hospital, Stockholm, Sweden, 1920-1959. Radium-226 sources were used in 12,821 patients, x-ray therapy was used in 2,515 patients, and no radiotherapy was given to 2,694 patients. Cancer incidence in the cohort was searched by record linkage with the Swedish Cancer Register for the period 1958-1982. The median age was 6 months for the treated patients and 8 months for the patients not receiving radiotherapy. In the group treated with radium-226 or orthovoltage x rays (greater than or equal to 100-kV peak), 224 cancers were observed [relative risk (RR) = 1.18; 95% confidence interval (CI) = 1.03-1.35]. In patients given contact x rays, 10 cancers were observed (RR = 0.71; 95% CI = 0.34-1.30). In patients not treated with ionizing radiation, 34 cancers were observed (RR = 0.93; 95% CI = 0.64-1.29). In patients treated with radium-226 or orthovoltage x rays, an RR of 1.65 was observed for breast cancer (95% CI = 1.26-2.13) and an RR of 2.73 was found for soft tissue tumors (95% CI = 1.18-5.38). Patients with brain tumors, thyroid cancers, and bone tumors had received radiotherapy close to the tumor site more often than expected. For patients with breast cancer, no such difference was found. For cancers of the breast and thyroid, the RR was higher in patients given more than one treatment.

Radiation dose and leukemia risk in patients treated for cancer of the cervix.

To quantify the risk of radiation-induced leukemia and provide further information on the nature of the relationship between dose and response, a case-control study was undertaken in a cohort of over 150,000 women with invasive cancer of the uterine cervix. The cases either were reported to one of 17 population-based cancer registries or were treated in any of 16 oncologic clinics in Canada, Europe, and the United States. Four controls were individually matched to each of 195 cases of leukemia on the basis of age and calendar year when diagnosed with cervical cancer and survival time. Leukemia diagnoses were verified by one hematologist. Radiation dose to active bone marrow was estimated by medical physicists on the basis of the original radiotherapy records of study subjects. The risk of chronic lymphocytic leukemia, one of the few malignancies without evidence for an association with ionizing radiation, was not increased [relative risk (RR) = 1.03; n = 52]. However, for all other forms of leukemia taken together (n = 143), a twofold risk was evident (RR = 2.0; 90% confidence interval = 1.0-4.2). Risk increased with increasing radiation dose until average doses of about 400 rad (4 Gy) were reached and then decreased at higher doses. This pattern is consistent with experimental data for which the down-turn in risk at high doses has been interpreted as due to killing of potentially leukemic cells. The dose-response information was modeled with various RR functions, accounting for the nonhomogeneous distribution of radiation dose during radiotherapy. The local radiation doses to each of 14 bone marrow compartments for each patient were incorporated in the models, and the corresponding risks were summed. A good fit to the observed data was obtained with a linear-exponential function, which included a positive linear induction term and a negative exponential term. The estimate of the excess RR per rad was 0.9%, and the estimated RR at 100 rad (1 Gy) was 1.7. The model proposed in this study of risk proportional to mass exposed and of risk to an individual given by the sum of incremental risks to anatomic sites appears to be applicable to a wide range of dose distributions. Furthermore, the pattern of leukemia incidence associated with different levels of radiation dose is consistent with a model postulating increasing risk with increasing exposure, modified at high doses by increased frequency of cell death, which reduces risk.

Dosimetric characterization of two radium sources for retrospective dosimetry studies.

PURPOSE: During the first part of the 20th century, (226)Ra was the most used radionuclide for brachytherapy. Retrospective accurate dosimetry, coupled with patient follow up, is important for advancing knowledge on long-term radiation effects. The purpose of this work was to dosimetrically characterize two (226)Ra sources, commonly used in Sweden during the first half of the 20th century, for retrospective dose-effect studies. METHODS: An 8 mg (226)Ra tube and a 10 mg (226)Ra needle, used at Radiumhemmet (Karolinska University Hospital, Stockholm, Sweden), from 1925 to the 1960s, were modeled in two independent Monte Carlo (MC) radiation transport codes: geant4 and mcnp5. Absorbed dose and collision kerma around the two sources were obtained, from which the TG-43 parameters were derived for the secular equilibrium state. Furthermore, results from this dosimetric formalism were compared with results from a MC simulation with a superficial mould constituted by five needles inside a glass casing, placed over a water phantom, trying to mimic a typical clinical setup. Calculated absorbed doses using the TG-43 formalism were also compared with previously reported measurements and calculations based on the Sievert integral. Finally, the dose rate at large distances from a (226)Ra point-like-source placed in the center of 1 m radius water sphere was calculated with geant4. RESULTS: TG-43 parameters [including gL(r), F(r, θ), Λ, and sK] have been uploaded in spreadsheets as additional material, and the fitting parameters of a mathematical curve that provides the dose rate between 10 and 60 cm from the source have been provided. Results from TG-43 formalism are consistent within the treatment volume with those of a MC simulation of a typical clinical scenario. Comparisons with reported measurements made with thermoluminescent dosimeters show differences up to 13% along the transverse axis of the radium needle. It has been estimated that the uncertainty associated to the absorbed dose within the treatment volume is 10%-15%, whereas uncertainty of absorbed dose to distant organs is roughly 20%-25%. CONCLUSIONS: The results provided here facilitate retrospective dosimetry studies of (226)Ra using modern treatment planning systems, which may be used to improve knowledge on long term radiation effects. It is surely important for the epidemiologic studies to be aware of the estimated uncertainty provided here before extracting their conclusions.

A new visible light DNA fluorochrome for confocal microscopy.

We have developed a new DNA-specific fluorochrome that is excited by visible light. This chemically uncharacterized fluorochrome readily penetrates tissue in whole mounts, gives a strong signal, is inexpensive to make and very easy to use. This preparation has several advantages over existing DNA fluorochromes in confocal laser microscopy applications. Many DNA fluorochromes are excitable by ultraviolet light. These have limited utility in confocal microscopy, where commonly used lasers produce only visible wavelengths of light. Other DNA fluorochromes are available that are excitable by visible light, but some have difficulty penetrating all cell types, while others have high background or fade quickly. This new fluorochrome overcomes these problems and has an emission spectra that makes it compatible with either rhodamine or Texas Red labeled reagents for double-label experiments. The ability to label all nuclei in a tissue and make three-dimensional reconstructions by confocal microscopy is extremely useful in examining cellular distributions within specific tissues.

Is there place for radiotherapy in the treatment of advanced ovarian cancer?

BACKGROUND AND PURPOSE: Irradiation of advanced ovarian cancer has been performed during the years 1976-1984 with six-field technique. Results of this treatment in a long follow-up have never before been evaluated. MATERIAL AND METHODS: Seventy-five patients with stage IIb-IV of invasive ovarian cancer have been treated with a combination of surgery, radiotherapy and chemotherapy. The results of the treatment were compared with 98 patients treated during the year 1991-1992 with surgery and chemotherapy only. RESULTS: After controlling for the differences in background factors between the groups considered, there was still a significantly better survival rate for the patients treated with radiotherapy. CONCLUSION: The results suggest that the role of radiotherapy in advanced ovarian cancer should be investigated in a prospective randomized trial.

Radiation therapy of ovarian carcinoma: presentation of a six-field technique.

A new technique for radiotherapy in ovarian carcinoma is presented. The aim was to deliver a homogeneous radiation dose to the entire abdominal cavity. The whole abdomen, except for 20% of the upper compartment, received a homogeneous dose of 40 Gy, while 2/3 of the kidneys and the posterior part of the liver received a dose ranging from 40 to 20 Gy. No clinically significant impairment of liver function was seen during follow-up.

Estimates of absorbed dose in different organs in children treated with radium for skin hemangiomas.

Between 1930 and 1959, more than 10,000 infants were treated at Radiumhemmet, Stockholm, with radium (226Ra) needles and/or tubes for hemangioma of the skin. Absorbed dose to the brain, eye lenses, parotid glands, thyroid gland, breast anlage, lungs, stomach, intestine, ovaries, testicles and bone marrow were calculated for each individual. The mean absorbed dose to the different organs ranged from 0.06 to 0.48 Gy. The highest absorbed dose was given to the breast (maximum 47.7 Gy). There was a wide dose range for each organ which was due mainly to differences in the distance between the applicator and the organ. The absorbed dose to all organs decreased on average by 32% during the study period. This was due to a 25% decrease in the treatment time and a change in the distribution of the treatment sites.

Mortality from leukemia after irradiation in infancy for skin hemangioma.

From 1920 through 1959, 14,624 infants were exposed to ionizing radiation for skin hemangioma at Radiumhemmet. They were all less than 18 months old (mean 6 months) at the time of first exposure. The irradiated hemangiomas were located all over the body. The weighted bone marrow dose was on average 0.13 Gy (range < 0.01-4.6 Gy). During the period 1920-1986, 20 deaths from leukemia (11 childhood and 9 adult) were observed in the cohort compared with 17 expected during the same period. There were no significant associations between childhood leukemia and radiation dose. Despite the relatively large number of infants studied, the low average dose to bone marrow limited the possibility of detecting a small radiation risk as might be predicted from other radiation studies.

Thyroid cancer after radiotherapy for skin hemangioma in infancy.

A Swedish cohort of 14,351 infants exposed to ionizing radiation for skin hemangioma was analyzed with respect to thyroid cancer risk. The subjects were irradiated during the period 1920-1959 and radiotherapy was given with beta particles, gamma rays and/or X rays. The mean absorbed dose to the thyroid was 0.26 Gy (range < 0.01-28.5 Gy). The cohort was matched with the Swedish Cancer Register for the period 1958-1986. Seventeen thyroid cancers were registered (standardized incidence ratio = 2.28; 95% confidence interval 1.33-3.65), and the mean thyroid absorbed dose in those subjects was 1.07 Gy (range < 0.01-4.34 Gy). The effect of different variables on the incidence of thyroid cancer was evaluated with Poisson regression. The excess in thyroid cancer began 19 years after radiotherapy and persisted at least 40 years after irradiation. A statistically significant dose-response relationship was found. The excess relative risk per gray was 4.92 (95% CI 1.26-10.2) and the excess absolute risk was 0.90 x 10(-4) per person-year gray. No significant difference in excess relative or absolute risk could be seen between the sexes.

Lenticular opacities in individuals exposed to ionizing radiation in infancy.

Development of lens opacities and the measures taken to avoid them have clinical relevance in the fields of oncology, radiotherapy and radiation protection. The aim of this study was to correlate the prevalence of lenticular opacities in individuals exposed to ionizing radiation in childhood with radiation dose and other possible risk factors. Between 1920 and 1959, about 16,500 children (age <18 months) with skin hemangiomas were referred to Radiumhemmet, Karolinska University Hospital, 89% of whom were treated with radiotherapy. A total of 484 exposed individuals and 89 nonexposed controls participated in an ophthalmological examination. Lens opacities were found in 357 (37%) of the 953 lenses examined in the exposed persons. In contrast, lens opacities were observed in only 35 (20%) of the 178 lenses examined in the nonexposed control individuals. It is concluded that the increased prevalence of cortical and posterior subcapsular opacities is related to previous radiotherapy. Age at examination was the strongest modifier of risk. Children exposed to a lenticular dose of 1 Gy had a 50% increased risk (odds ratio 1.50; 95% confidence interval 1.10-2.05) of developing a posterior subcapsular opacity and a 35% increased risk of a cortical opacity (odds ratio 1.35; 95% confidence interval 1. 07- 1.69).

Breast cancer after radiotherapy for skin hemangioma in infancy.

Between 1920 and 1959, 9675 women were irradiated in infancy for skin hemangioma at Radiumhemmet, Stockholm. They were exposed to low to moderate doses of ionizing radiation. The mean age at first exposure was 6 months and the mean absorbed dose to the breast anlage was 0.39 Gy (range <0.01-35.8 Gy). The breast cancer incidence was analyzed by record linkage with the Swedish Cancer Register for the period 1958-1986. Seventy-five breast cancers were found [standardized incidence ratio = 1.24; 95% confidence interval (CI) 0.98-1.54] after a mean absorbed dose of 1.5 Gy in the breasts with cancer. The analyses showed a significant dose-response relationship with a linear model estimate for the excess relative risk (ERR) of 0.38 at 1 Gy 95% CI 0.09-0.85). This relationship was not modified significantly by age at exposure or by dose to the ovaries. The ERR increased significantly with time after exposure and for > or = 50 years after exposure the ERR at 1 Gy was 2.25 (95% CI 0.59-5.62). The fitted excess absolute risk (EAR) was 22.9 per 10(4) breast-year gray. The breast absorbed dose and time after exposure were important risk determinants for breast cancer excess risk. Forty to 50 years of follow-up was necessary for the excess risk to be expressed. The study confirms previous findings that the breast anlage of female infants is sensitive to ionizing radiation.

Outcome of reproduction in women irradiated for skin hemangioma in infancy.

The possible impact of early gonadal irradiation on the results of future pregnancies is unclear. This study is based on the progeny of 17,393 women who were treated with irradiation for skin hemangiomas at the age of 18 months or less. The mean ovarian dose was 6 cGy, and the maximum was 8.55 Gy. Using Swedish central health registers, the outcome of delivery was studied in these women; 19,494 infants born were identified. The treated women deviated from the general population by having a longer education and by smoking less. This may explain a reduced risk for low birth weight and preterm birth (not related to radiation dose). Women with ovarian doses greater than 1 cGy had fewer infants than women with a lower ovarian dose. An excess of perinatal deaths was evident as well as a slight excess in the rate of malformation, but neither was related to dose. There was a statistically significant trend of an increasing rate of neural tube defects with ovarian dose, possibly a chance result of multiple statistical testing. Cleft lip/palate occurred at levels significantly below expectation. No increase in the rate of infants with Down syndrome or in childhood malignancies was detected. No major adverse results in outcome of delivery were seen after ovarian irradiation in childhood with the possible exception of neural tube defects.

Breast cancer risk after radiotherapy in infancy: a pooled analysis of two Swedish cohorts of 17,202 infants.

The incidence of breast cancer was studied in a cohort of 17,202 women irradiated for skin hemangioma in infancy at the Radiumhemmet, Stockholm, or the Sahlgrenska University Hospital, Gothenburg. A major part of the cohort had been treated with radium-226 applicators, and the mean absorbed dose to the breasts was 0.29 Gy (range <0.01-35.8 Gy). Two hundred forty-five breast cancers were diagnosed in the cohort during the period 1958-1993, and the standardized incidence ratio (SIR) was 1.20 (95% CI 1.06-1.36). Different dose-response models were tested, and a linear model gave the best fit. Neither age at exposure, breast dose rate, ovarian dose nor time since exposure had any statistically significant modifying effect, and breast dose was the only determinant of risk. The excess relative risk per gray (ERR/Gy) was 0.35 (95% CI 0.18-0.59), which is lower than in most other studies.

Intracranial tumors after exposure to ionizing radiation during infancy: a pooled analysis of two Swedish cohorts of 28,008 infants with skin hemangioma.

The risk of intracranial tumors after exposure to ionizing radiation during infancy has been studied in a pooled analysis of two Swedish hemangioma cohorts (n = 28,008). The mean absorbed intracranial dose was low (7 cGy, range 0-11.5 Gy). The cohorts were followed up in the Swedish Cancer Register for incident intracranial tumors during the period 1958-1993. Eighty-eight tumors were found in 86 individuals compared to 60.72 expected [standardized incidence ratio (SIR) 1.42, 95% confidence interval (CI) 1.13-1.75]. The SIR increased significantly in ascending dose categories (P = 0.02). Dose-response analyses were performed with Poisson regression methods. There was a significant effect of dose, and the dose-effect relationship was negatively modified by age at first treatment. This indicates a higher risk for those exposed earlier in life. A linear dose-response model modified by age at first treatment resulted in the best fit. The excess relative risk (ERR) was 2.7/Gy (95% CI 1.0-5.6). The ERR/Gy was 4.5 if the treatment was given before 5 months of age, 1.5 if it was given at 5-7 months and 0.4 if it was given later. The study thus strongly indicates that there exists a dose-response relationship between absorbed dose in the brain and the subsequent risk of developing an intracranial tumor and that the risk is higher among infants exposed at younger ages.

Blood flow changes in the rabbit maxilla following an anterior osteotomy.

This investigation considered circulatory changes in the distal segment of an anterior maxillary osteotomy produced in nine rabbits. Blood flow in the distal pulp, alveolar bone, and mucosa was measured using hydrogen washout. The results showed a decrease in blood flow in all tissues with a mucosal rebound within 30 min.

Measurement of regional bone blood flow in the rabbit mandible using the hydrogen washout technique.

This investigation involved quantitating blood flow in rabbit mandible using the hydrogen washout technique. The animal was ventilated with a H2/O2 gas mixture. Hydrogen concentration was monitored by surgically implanted platinum electrodes. The Fick principle was used to interpret the H2 washouts. The following mean flows were obtained: Cortical bone, 4.49 ml/100g/min; condylar bone, 8.22 ml/100g/min; and alveolar bone, 18.33 ml/100g/min. This technique proved repeatable and compared well with other studies.

Estimation of the radiation dose from radiotherapy for skin haemangiomas in childhood: the ICTA software for epidemiology.

Radium applicators and pure beta emitters have been widely used in the past to treat skin haemangioma in early childhood. A well defined relationship between the low doses received from these applicators and radiation-induced cancers requires accurate dosimetry. A human-based CT scan phantom has been used to simulate every patient and treatment condition and then to calculate the source target distance when radium and pure beta applicators were used. The effective transmission factor psi(r) for the gamma spectrum emitted by the radium sources applied on the skin surface was modelled using Monte Carlo simulations. The well-known quantization approach was used to calculate gamma doses delivered from radium applicators to various anatomical points. For 32P, 90Sr/90Y applicators and 90Y needles we have used the apparent exponential attenuation equation. The dose calculation algorithm was integrated into the ICTA software (standing for a model that constructs an Individualized phantom based on CT slices and Auxological data), which has been developed for epidemiological studies of cohorts of patients who received radium and beta-treatments for skin haemangioma. The psi(r) values obtained for radium skin applicators are in good agreement with the available values in the first 10 cm but higher at greater distances. Gamma doses can be calculated with this algorithm at 165 anatomical points throughout the body of patients treated with radium applicators. Lung heterogeneity and air crossed by the gamma rays are considered. Comparison of absorbed doses in water from a 10 mg equivalent radium source simulated by ICTA with those measured at the Radiumhemmet, Karolinska Hospital (RAH) showed good agreement, but ICTA estimation of organ doses did not always correspond those estimated at the RAH. Beta doses from 32P, 90Sr/90Y applicators and 90Y needles are calculated up to the maximum beta range (11 mm).

The Swedish Transplant Coordinators' experience of the new Transplantation Act and the donor register 1 year after implementation.

The register has been a support for the coordinators in Sweden when the relatives have said one thing and the deceased person another in regards to donation. Most of the staff are positive to the register and the safety regulations around it. Most often it has been a relief for the relatives that the deceased person's wishes also have been documented in the register or in the donor card. Most decisions are still, however, made by relatives. There is still a need for more positive information about transplantation and its value.