Multi-directional positron imaging: evaluation of cancer detection with 2-(F-18)-fluoro-2-deoxy-D-glucose.

We developed a multi-directional positron imaging system for the whole body in order to evaluate the spatial distribution of radiopharmaceuticals. A positron emission tomography (PET) scanner with ring detectors was modified to provide 54 directional planar images with a three-dimensional appearance by using cinematic display. The initial clinical evaluation was performed on two normal volunteers and 17 cancer patients with 32 foci. Images were obtained approximately one hour after the intravenous administration of 2-(F-18)-fluoro-2-deoxy-D-glucose. In all 19 subjects, good quality images with a three-dimensional appearance were obtained. We were able to visualize 16 of 20 (80%) lesions that were three centimeters or more in greatest diameter. In contrast, only seven of 12 (58%) lesions less than three centimeters in greatest diameter were identified. The overall detectability of lesions was 72%. These results suggest that this system will be useful for tumor detection.


Clinical experience with a single field rotational total skin electron irradiation technique for cutaneous T-cell lymphoma.

Between October 1981 and December 1989, 44 patients with cutaneous T-cell lymphoma (CTCL) were treated with a single field rotational total skin electron irradiation (RTSEI) technique developed in the McGill University, Department of Radiation Oncology. Only 11 (25%) of the 44 patients had received no prior treatment. Three-quarters (33/44) had advanced (T3 or T4) disease. Complete responses were seen in 32/44 (73%) of patients (91% T2, 71% T3 and 58% T4), but only 3/11 (27%) of patients with T2 disease and 3/21 (14%) of patients with T3 disease remain in continuous complete remission in the skin, after median intervals of 58 and 35 months, respectively. Median cause-specific survival for the whole group is 43 months and survival at 5 years is 38%. Survival was significantly better for patients with T2 disease than for patients with T3 disease (relative risk 4.3; 95% CI 1.4-13.2) and patients with T4 disease (relative risk 3.1; 95% CI 0.8-12.1). The RTSEI technique used at McGill has depth-dose characteristics and photon contamination similar to other commonly used TSEI techniques. It is relatively simple and provides a homogenous dose distribution over the entire skin surface in a short treatment time. Results of treatment are similar to those obtained with other techniques. For T2 disease, TSEI is an effective treatment modality with a possibility of long-term tumor control. For more advanced disease, more aggressive treatment, which may include TSEI, is necessary.


A Japanese adult case of cystic fibrosis causing bone demineralization.

Cystic fibrosis is an inherited, multisystem disorder characterized by an abnormality in exocrine gland function. It leads to chronic pulmonary disease in most cases and pancreatic insufficiency in 85 percent of patients. Although this disease is not uncommon in Caucasians, it has been considered very rare among Japanese. The majority of patients are diagnosed in infancy or childhood. The patient in this case report was a 45-year-old Japanese man who had not been diagnosed as having cystic fibrosis. This patient had recurrent episodes of pulmonary infection that started in childhood, and plain films of the chest showed increased interstitial markings, hyperaeration, and bronchiectasis. CT of the upper abdomen showed a generally enlarged pancreas with complete fatty replacement. Serum and urine pancreatic enzyme levels were low, suggesting pancreatic insufficiency. Repeated sweat tests were positive. A roentgenologic skeletal survey showed general demineralization, which may be multifactorial. In this case, it was concluded that vitamin D deficiency caused by vitamin D malabsorption and/or insufficient sunlight exposure was mainly responsible for the demineralization and that chronic respiratory acidosis might also be partially responsible.


Imaging in cardiac mass lesions.

In 26 patients with cardiac mass lesions confirmed by surgery, diagnostic imaging was performed preoperatively by means of two-dimensional echocardiography (26 patients), angiography (12 patients), correlative computed tomography (CT, 8 patients), and magnetic resonance imaging (MRI, 3 patients). Two-dimensional echocardiography correctly identified the cardiac masses in all patients. Angiography missed two of 12 cardiac masses; CT missed one of eight. MRI identified three of three cardiac masses. Although the sensitivity of two-dimensional echocardiography was high (100%), all methods lacked specificity. None of the methods allowed differentiation between myxoma (n = 13) and thrombus (n = 7). Malignancy of the lesions was successfully predicted by noninvasive imaging methods in all six patients. However, CT and MRI provided additional information concerning cardiac mural infiltration, pericardial involvement, and extracardiac tumor extension, and should be integrated within a preoperative imaging strategy. Thus two-dimensional echocardiography is the method of choice for primary assessment of patients with suspected cardiac masses. Further preoperative imaging by CT or MRI can be limited to patients with malignancies suspected on the grounds of pericardial effusion or other clinical results.


Carcinomas of the nasal cavity.

Between 1969 and 1985, 45 patients with carcinomas of the nasal cavity proper received curative treatment. Thirty patients had squamous cell carcinoma, one had undifferentiated carcinoma, 9 had adenocarcinoma, and 5 had adenoid cystic carcinoma. Eighteen patients were treated with definitive radiotherapy (interstitial brachytherapy in 5 and external beam therapy in 13 patients), and 27 received surgery and radiotherapy. The median length of follow-up was 11 years (range: 2.8-16.8 years). Thirty-six patients had no evidence of disease at the last follow-up visit. All 14 patients with carcinoma of the nasal septum had the disease controlled. Nine of 31 patients with lesions of the lateral wall and floor died of the disease, 5 of uncontrolled local disease, 2 of distant metastases, and 2 of both. The disease-specific survival rates at 5 and 10 years were 83 and 80%, respectively, and the corresponding overall survival rates were 75 and 60%, respectively. Blindness occurred in 4 patients, 2 due to orbital exenteration and 2 to radiation injury to the cornea and optic pathway. Other infrequent side effects were bone necrosis, dental decay, nasal stenosis, and septal perforation. This study indicated that the prognosis of patients with nasal cavity carcinoma was better than that of patients with maxillary sinus cancer treated during the same era. In addition, the study showed that carcinomas of the nasal septum were smaller than those of lateral wall and floor at diagnosis, so that excellent control could be achieved by definitive radiotherapy; when accessible, interstitial brachytherapy might be the treatment of choice in such patients.


The effect of unlabelled monoclonal antibody (mAb) on the biodistribution of 131I-anti-idiotype mAb in murine B cell lymphoma.

The 38C13 murine B cell lymphoma model was used to study the effect of the preinjection of unlabelled anti-idiotype monoclonal antibody (mAb) on the subsequent biodistribution of 131I-anti-idiotype mAb. Mice with established tumors received 0-500 micrograms of unlabelled anti-idiotype mAb 24 h prior to the administration of 131I-anti-idiotype (specific), or both 125I-anti-idiotype and 131I-isotype-matched irrelevant control (nonspecific) mAb. Mice were counted daily in a gamma counter and sacrificed at 2-144 h following injection. Mice were dissected and the weight and activity of the animals and organs were measured. Mice were bled periodically and circulating idiotype levels were measured using an ELISA assay. Five hundred micrograms of unlabelled anti-idiotype mAb increased the retention time of the specific but not the nonspecific mAb in all organs and tumor. Following pretreatment with unlabelled mAb, the cumulative tumor/whole body and tumor/normal organ ratios became similar to those of the nonspecific mAb, with concentration ratios (specific/nonspecific mAb) of approximately 1, which persisted until 96 h post injection when circulating idiotype reappears in antigen excess. In the absence of unlabelled mAb there was less retention in tumor and normal tissue. This is presumed to be due in part to decreased levels of circulating 131I-mAb secondary to rapid plasma clearance of antigen-antibody complexes and tumor cell mediated dehalogenation, which results when the specific mAb specifically binds the targeted antigen. Thus, the addition of unlabelled mAb increased the retention by decreasing the specific behavior of the anti-idiotypic antibody.


Unusual complication of liver irradiation: acute thrombosis of a main hepatic vein: CT and MR imaging features.

The pathologic changes resulting from liver irradiation include congestion, fibrosis, and veno-occlusive disease. We report an unusual complication of radiation induced injury: acute thrombosis of a main hepatic vein within the radiation port. CT and MR features are described and the etiology of this unusual complication is discussed.


Mouse hemithoracic irradiation and its interaction with cytotoxic drugs.

Irradiation of the mouse right or left hemithorax at 14 or 18 Gy produced a dose-dependent rise in breathing rate 16 weeks after irradiation without significant mortality. The measurement of breathing rate changes following right hemithoracic irradiation combined with the maximally tolerated dose of cytotoxic drugs was assessed as a method for qualitatively detecting drug-irradiation interactions which either exacerbate pneumonitis or alter its time course. Cyclophosphamide at 100 mg/kg accentuated and accelerated the rise in breathing rate, culminating in early mortality. BCNU 30 mg/kg delayed the appearance of the radiation response. Busulphan 30 mg/kg appeared to be radioprotective, but this was shown to be due to the DMSO-containing vehicle. Doxorubicin 6 mg/kg had no effect when combined with right or left hemithoracic irradiation. Carboplatin 100 mg/kg, vindesine 4 mg/kg and vinblastine 4 mg/kg had no substantial effect upon the changes in breathing rate.


The use of large fractions in radiotherapy for malignant melanoma.

Eighty-nine cutaneous, subcutaneous or lymph node metastases of malignant melanoma in 15 patients were treated with radiotherapy using electron beams at appropriate energies (6-15 MeV). A total dose of 40 Gy was given in 8 fractions (fraction size 5 Gy) over 23 days. The therapy was given as two weekly fractions on two consecutive days with a 24-h interval. The next two fractions were given after a pause of 6 days. Eighty-six of 89 lesions (97%) responded to treatment, response rate being clearly dependent on tumour size. All the 67 lesions less than 2 cm in diameter responded, 51 of them (78%) completely disappearing, while in tumours over 4 cm among 10 lesions only 2 CR lesions were achieved. In cases where prolonged follow-up (greater than one year) was possible no major late side-effects were observed. The treatment scheme with large fractions appears to be well-tolerated and effective for metastatic malignant melanoma.


Computed tomographic findings of small-bowel volvulus.

Computed tomographic examinations of two cases of small-bowel volvulus were reviewed. At laparotomy, both cases were proved to be secondary to adhesions. CT examinations showed focal, wedge-shaped, edematous mesentery with trapped fluid between mesenteric folds radiating toward the site of torsion. One case showed the superior mesenteric vein spiraling around the superior mesenteric artery. At laparotomy, affected small-bowel loops showed ischemia in both cases. CT performed in patients with acute abdomen may show findings suggestive of small-bowel volvulus.


The clinical application of a non-axial treatment plan for pancreatic and biliary malignancies.

Standard radiation therapy for adenocarcinoma of the pancreas treats a substantial portion of the renal parenchyma. It was hypothesized that rotating the plane of treatment to a non-axial orientation, with the anterior field entering the patient from an inferior oblique direction, would decrease the renal dose of radiation without increasing the liver dose or compromising the target dose. To test this hypothesis, patients referred for radical radiation treatment for tumors of the pancreas or distal common bile duct were prospectively evaluated by performing treatment planning using axial and non-axial field arrangements. Treatment plans were compared using dose volume histograms (DVHs) of both kidneys and the liver. In all 15 cases analyzed, the non-axial plan was superior to the axial plan with respect to renal dose, without significantly increasing the hepatic dose and was used for treatment. Treatment was not significantly more complex nor was gastrointestinal toxicity increased. These findings show that non-axial field arrangements can be used on a routine basis to decrease the renal dose of radiation for the treatment of pancreatic and biliary malignancies. It is anticipated that in the future, a combination of DVH-guided treatment planning and sophisticated renal function studies will be necessary to permit a more accurate prediction of the probability of renal complications resulting from radiation therapy.


The effect of the hypoxic cell drug SR-4233 alone or combined with the ionizing radiations on two human tumor cell lines having different radiosensitivity.

The influence of the hypoxic cell drug, SR-4233, alone and/or combined with ionizing radiations on the survival of two human cell lines having very different intrinsic radiosensitivity was analysed. The killing effect of SR-4233 in hypoxia was similar for both cell lines. Twenty microM SR-4233 under hypoxic conditions had a killing effect equivalent to 6.6 Gy for the poorly sensitive cell line (HT29) and equivalent to 3.9 Gy for the highly sensitive cell line (SW48). The effect of SR-4233 and ionizing radiations on these two cell lines was tested in vitro: the cells were incubated for one hour in hypoxia with or without 20 microM SR-4233 and then irradiated in air. The HT29 cells that survived treatment with SR-4233 are more radiosensitive than untreated cells. However, their radiosensitivity is similar to that of cells that have been given a dose of 6.6 Gy. This suggests that SR-4233 acts additively, rather than as a radiosensitiser. As SR-4233 acts selectively in hypoxia, these results appear encouraging for the treatment of poorly-radiosensitive human tumors.


The effect of increasing the treatment time beyond three weeks on the control of T2 and T3 laryngeal cancer using radiotherapy.

Local control of cancer by radiotherapy may be prejudiced by accelerated tumour clonogen repopulation particularly during protracted treatment schedules. A series of 496 cases of T2 and T3 larynx cancer treated here by radiotherapy has been studied to examine the impact on local control of treatment durations ranging from 9 to 41 days. Data were analysed using a linear-quadratic formulation describing the fractionation sensitivity, with the incorporation of a parameter relating to treatment time. Using combined T2 and T3 data, the increase in dose required to maintain a constant local control (the time factor) was between 0.5 and 0.6 Gy per day. These values are similar to those reported for 4 weeks or more in the literature. Also, the calculated dose to control 50% of tumours, given over the standard Christie duration of 21 days, was on the line projected back from literature data over 28-66 days. The present data are consistent with the presence of such a time factor following a lag phase of not more than 3 weeks after starting radiotherapy. Hence, further consideration should be given to using shorter overall treatment times in radiotherapy for head and neck cancer.


Aggressive treatment of intrathoracic recurrences of thymoma.

Between 1974 and 1988, 21 patients with intrathoracic recurrences of thymoma received radiotherapy with radical intent; surgery was always attempted when considered feasible: 11 patients were partially (6 cases) or totally (5 cases) resected before irradiation, while in the other 10 radiotherapy was the only treatment. In 7 cases the recurrence was confined to the anterior mediastinum, 9 had pleural nodules without mediastinal lesions and 5 had both mediastinal and pleural lesions. Mediastinal recurrences were treated by opposed parallel mediastinal fields with 2/3 of the dose delivered through the anterior port: doses ranged between 38 and 44 Gy; a boost of 10-16 Gy was given in patients not radically resected. Pleural nodules were treated with a variety of techniques according to the extent of the lesions. The 7-year survival of the whole group was 70%; 5 patients died: 4 with intrathoracic progression and one with distant metastases. The survival was 74% in the 11 patients having received surgery, either radical or subtotal, and 65% in the 10 patients treated with radiotherapy alone: the difference is not significant. Patients with Karnofsky index greater than 70 had a significantly better survival (100%, versus 28%, p = 0.0015). This is a selected series of patients presenting recurrences still amenable to a radical treatment either by surgery and radiotherapy or by radiotherapy alone: the results confirm that an aggressive approach is warranted in patients in good general conditions with recurrences confined to the mediastinum and/or 1 hemithorax.


The use of asymmetric-field inversion gel electrophoresis to predict tumor cell radiosensitivity.

The success of a predictive assay for radiotherapy relies on the use of one or more tumor cell traits that equate with tumor radioresistance or radiosensitivity. These traits can be divided into intrinsic (genetic) and extrinsic (epi-genetic) factors. Most probably, a tumor's response to radiotherapy will be influenced by both of these sets of traits. Radiobiological analysis of cultured cells derived from explanted tumors of head and neck patients has shown that in vitro survival of tumor cells is not the only factor affecting tumor radiocurability. Two possible reasons are the high degree of selection involved in growing the cells in vitro and the inability to assess the contribution of the cell-cell contact effect with cultured cells. A possible means of overcoming both of these problems would be an assessment of the radiosensitivity of the cell population immediately after removal from the tumor. Since a good correlation exists between intrinsic cellular radioresistance and DNA double-strand break repair (DSBR) as assayed by the Neutral Elution technique [21], we have investigated the feasibility of using asymmetric field inversion gel electrophoresis (AFIGE) in identifying resistant tumor cells in vitro. AFIGE has several advantages over neutral elution in that it is faster (approximately 60-80 samples can be run on the same agarose gel) and, most importantly, one can visualize DNA damage and repair by staining the DNA with ethidium bromide.(ABSTRACT TRUNCATED AT 250 WORDS)


Potentiation of alkylating chemotherapy by dual function nitrofurans in multi-cell spheroids and solid tumors.

The cytotoxicity and chemosensitizing potential of four dual function nitrofurans was determined in human HT-29 multi-cell spheroids and rodent KHT sarcoma solid tumors. Spheroids were treated with a range of doses of the bioreductive drugs for a period of up to 48 h and the extent of cell kill was assessed at various times after treatment. Cytotoxicity was determined using a clonogenic cell-survival assay. The results demonstrated that two of the nitrofurans were even more toxic to spheroid cells than was the potent bioreductive nitroimidazole aziridine RSU 1069. The dose of the nitrofuran which, after a 24-h exposure, led to a survival value between 0.5 and 1.0, then was chosen for subsequent studies aimed at assessing the ability of these agents to potentiate the efficacy of the nitrosourea CCNU. Exposure to this chemotherapeutic agent was for a period of 1 h. The results indicated that all four dual function nitrofurans enhanced the cell killing of the conventional chemotherapeutic agent by factors ranging from 1.1 to 1.7. Subsequent studies evaluated the therapeutic benefit of combining these bioreductive agents and CCNU in KHT sarcoma-bearing C3H/HeJ mice. The nitrofurans were administered i.p. 0.5 h prior to the chemotherapy and tumor response was assessed by measuring the survival of clonogenic KHT cells 22-24 h after treatment. Normal tissue toxicity was determined using a bone marrow stem cell (CFU-GM) assay. Combining these bioreductive agents with CCNU increased the tumor cell kill by factors of 1.2 to 1.7.(ABSTRACT TRUNCATED AT 250 WORDS)


Radiosensitizing and repair-inhibiting properties of dipyridamole.

Radioresistance and postirradiation repair of potentially lethal damage (PLD repair) are important factors underlying failure to control local disease in cancer. Dipyridamole (DP) is known as a modifier of the action of cytotoxic drugs. We therefore investigated DP as a potential radiosensitizer and inhibitor of PLD repair in X-irradiated Chinese hamster ovary (CHO) cells in vitro. Exposure to the drug alone resulted in a slight reduction of the clonogenic capacity of the cells. Preincubation for 18 h with 10 and 20 microM DP in cells subcultured at low density, led to a significant radiosensitization. In confluent density-inhibited cultures, preincubation alone as well as pre- and postincubation with 20 microM DP resulted in a significant inhibition of PLD repair. Dipyridamole and related compounds may thus be useful tools for modifying and investigating the response of mammalian cells to radiation.


A practical evaluation of five dose-volume histogram reduction algorithms.

A unifying approach to cumulative dose-volume histogram (CDVH) reduction analysis is presented, utilising two weighted linear interpolation models (VWD, DWV), two weighted probability models (VWP, DWP) and a novel integral probability model (IPM). As a test of their predictive value these algorithms were applied to CDVH data generated from lung doses, measured by TLD arrays in a female anthropomorphic phantom. Three arbitrary configurations of breast size and location of "target volume" within the breast were "treated", using an appropriate electron field (Varian Clinac 1800) or double-plane iridium-192 implant. Calculated effective doses from each of the reduction algorithms showed the iridium implant to be dosimetrically the most favourable in two the three configurations. Likewise, complication probabilities, based on a logistic dose-volume response function showed lung complication probabilities to be lower for the interstitial technique in the same situations. All algorithms tested showed reasonable consistency, with the exception of the VWD. The rationale and value of comparative rather than absolute dose-volume histogram analyses are discussed.


Maximizing setup accuracy using portal images as applied to a conformal boost technique for prostatic cancer.

A design procedure of a patient setup verification protocol based upon frequent digital acquisition of portal images is demonstrated with an application for conformal prostatic boost fields. The protocol aims at the elimination of large systematic deviations in the patient setup and includes decision rules which indicate when correction of the patient setup is needed. The decision rules were derived from the results of a theoretical and quantitative analysis of patient setup variations measured in three pelvic fields (one anterior-posterior and two lateral fields) of 105 fractions for nine patients. Deviations in the patient positioning, derived from one field, were quantified as two-dimensional (2-D) displacement vectors in the plane perpendicular to the beam axis by alignment of anatomical features in the portal and the simulator image. The magnitude of the overall setup variations along the anterior-posterior, superior-inferior and lateral directions varied between 2.6 and 3 mm (1 S.D.). Inter- and intra-treatment variations could be separated, both having equal magnitudes of 1.7 to 2.2 mm (1 S.D.). In addition, intra-treatment variations appeared to be predictable which was a prerequisite for the development of the decision rules. The 2-D setup deviations, measured in the three fields of one fraction were strongly correlated and a 3-D displacement vector was calculated. Utilization of this 3-D vector in a setup verification protocol may lead to an early detection of systematic setup deviations.


Primary radiotherapy of breast cancer: treatment results in locally advanced breast cancer and in operable patients selected by positive axillary apex biopsy.

To evaluate the efficacy of radiotherapy without surgery, treatment results in patients treated for locally advanced breast cancer (n = 209) and those selected by positive axillary apex biopsy (n = 289) in the period between 1977 and 1985 have been analysed retrospectively. Treatment consisted of primary irradiation to the breast and regional lymph nodes followed by a boost to the primary breast tumour and palpable regional disease to a mean normalised total dose (NTD) of 64.7 Gy with a range of 33.4-93 Gy (2 Gy fractions, alpha/beta = 5 Gy). Adjuvant systemic treatment was given in 30% of the locally advanced and in 40% of the apex positive patients. Thirty percent of the apex positive patients had an excisional biopsy of the breast tumour. By multivariate analysis a prognostic index is constructed for locoregional control, overall survival and distant disease-free interval. Primary tumour size and clinical nodal status are independent prognostic factors for locoregional control. Based on the prognostic index for local control four different groups can be identified with 5 year local control rates varying from 47 to 86%. Patients treated with adjuvant chemotherapy and patients irradiated to a NTD of 60 Gy or more had significantly better local control. For overall survival primary tumour size, clinical nodal size and age are independent prognostic factors. Patients irradiated to a NTD above 60 Gy had significantly better results. Survival according to the prognostic index for survival varies between 20 and 50% at 5 years for the four groups subdivided according to the index for survival. Primary tumour size, clinical node size and age are independent prognostic factors for distant disease-free interval. Patients treated with adjuvant hormonal therapy had significantly better results. In the four groups subdivided according to the prognostic index for distant disease-free interval results vary from 17 to 30% at 5 years.


The influence of mineralising radionecrosis on the dose distribution in interstitial radiation therapy of brain tumours.

The influences of radionecroses arising during interstitial radiation of brain tumours with 125I, 192Ir or 198Au on dose distribution was investigated using Monte Carlo methods. The necroses have a higher density than normal tissue due to radiation-induced changes in tissue composition as well as mineral deposits. They can have a diameter of up to 1 cm around the single seeds. The higher density and changed chemical composition compared to homogeneous normal tissue leads to increased absorption of radiation around the necroses which results in a lower dose rate in the surrounding tissue. It is shown that the formation of necroses during treatment with higher energy radiation such as 192Ir (340 keV) or 198Au (400 keV) may be neglected during therapy planning as the dose rate is affected by less than 2%. If low energy radiation, e.g. 125I (28 keV) is used, the dose rate can be reduced by more than 30%. In this case the influence of the necroses on dose distribution, at least for permanent 125I implantation, may not be negligible.


Cardiac doses in post-operative breast irradiation.

Data were collected on radiation doses given to the heart and coronary arteries during primary breast irradiation in order to analyze factors which might be important in the aetiology of subsequent cardiac-related disease. Twenty eight patients with breast cancer were studied. Fourteen patients treated from 1957 to 1984 were studied retrospectively (group 1), and 14 treated from 1988 to 1989 were studied prospectively (group 2). All patients had stage I or II disease at presentation, and were under 70 years of age. None had chemotherapy as a primary form of treatment. Patients were given a computed tomography scan of the chest, and three-dimensional reconstruction was made of the heart, lung and body contour. Original dose distributions were super-imposed on these outlines, and doses to the total cardiac volume and three main coronary arteries were estimated using an alpha/beta ratio of 4 Gy. Nine out of 14 patients in group 1 had a mastectomy followed mainly by orthovoltage radiation with similar techniques used up until 1984. Thirteen out of 14 patients in group 2 had conservative surgery followed by a modern two- or four-field megavoltage technique. We found that for patients with left-sided tumours (n = 20), the heart volume irradiated to a minimum extrapolated target dose of 5 Gy is significantly decreased for patients treated with a modern technique (group 2) when compared with those treated with earlier techniques (group 1).(ABSTRACT TRUNCATED AT 250 WORDS)


Vestibular apparatus disorders after external radiation therapy for head and neck cancers.

External irradiation of different head and neck cancers may involve parts of the ear. The vestibular function of 25 patients in which the inner ear was comprised in the irradiated volume was investigated by electronystagmography (ENG). Doses administered to the vestibular system ranged between 2800 and 5120 cGy. Five patients suffered subjective vertigo or dizziness. Eleven patients (three out of five with vertigo) showed vestibular abnormalities to ENG (44% of the total). Altered responses to specific tests were as follow: six patients to the bithermal caloric stimulation, two to the pendular-sinusoidal test and the other three to both of them. Patients were evaluated 3 and 6 months after the ending of the radiation therapy course. At the first evaluation, abnormalities to caloric test were noted in three patients (12%) and to sinusoidal rotatory test in one patient (4%). At the second evaluation, rates of abnormal response increased to 36% and 20%, respectively. Vestibular disorders seemed to be scantly related to the total radiation dose. Data of literature are discussed in order to identify possible implications on treatment planning.


Hypothyroidism following radiotherapy for head and neck cancer: multivariate analysis of risk factors.

The incidence of hypothyroidism following radiotherapy for head and neck cancer is 10-45% in several series. In order to identify possible risk factors a multivariate analysis was performed in 221 patients previously treated with either radiotherapy alone or combined with surgery or chemotherapy. Diagnostic procedures included: total T3 and T4, free T4 and TSH measured by radioimmunoassay, and thyroid scintigraphy. The absolute rate of hypothyroidism was 41.17% (subclinical 26.24%, clinical 14.93%). No thyroid nodules were detected in any patient. By multivariate analysis, risk factors that significantly influenced a higher incidence of hypofunction were: high radiation dose (p = 0.000), combination of radiotherapy and cervical surgery (p = 0.003), time from therapy (p = 0.022) and no shielding of midline (p = 0.026).


BW12C-induced changes in haemoglobin-oxygen affinity in mice and its influence on the radiation response of a C3H mouse mammary carcinoma.

The effect of the substituted benzaldehyde BW12C on haemoglobin-oxygen binding affinity, tumour radiation response and blood perfusion were investigated in a C3H mouse mammary carcinoma grown in the feet of CDF1 mice. Mouse P50 (partial pressure of oxygen at half saturation) was estimated using an ABL blood gas analyzer; radiation response determined from tumour regrowth and local tumour control assays; and tumour blood perfusion measured with a 86RbCl extraction procedure. A single intravenous injection of BW12C substantially decreased mouse P50. This effect was dependent on the time after injection with the nadir observed within 15 min and only returning to normal after several hours. It was also dependent on drug dose, the decrease becoming larger with increasing concentration, reaching a maximum 50% reduction at 70 mg/kg. The decrease in P50 could be maintained for at least 6 h following injection of 70 mg/kg, if mice were also given 25 mg/kg at hourly intervals. However, no changes in radiation response or tumour blood perfusion were observed with either single or multiple administrations of BW12C. These results suggest that BW12C induced changes in tumour hypoxia reported by several groups of workers, may not be entirely the result of a change in haemoglobin-oxygen affinity.


Pharmacokinetics of nicotinamide and its effect on blood pressure, pulse and body temperature in normal human volunteers.

The pharmacokinetics of nicotinamide were studied in four human volunteers after oral doses of 1-6 g. Plasma concentrations and clearance rates of the vitamin were found to be dose-dependent, with a half-life of approximately 7-9 h for the two highest doses administered (4 and 6 g), approximately 4 h with 2 g and approximately 1.5 h with a 1-g dose. Peak concentrations ranged from 0.7 to 1.1 mumol.ml-1 after a 6-g dose. The time to reach peak plasma concentration was dose independent with a broad range from 0.73 to 3 h. In this study, nicotinamide had no detectable effect on blood pressure, pulse or body temperature.


A pilot study of a method of estimating the number of functional eccrine sweat glands in irradiated human skin.

Following stimulation with pilocarpine, the secretion from eccrine sweat glands produces characteristic imprints in hardening silicone polymers applied to the skin. This permits an accurate determination of the numerical density of functional eccrine glands in irradiated skin which can be compared to non-irradiated skin. A description of this inexpensive, noninvasive, and quantitative technique is presented as well as preliminary results determined in six normal subjects and 28 irradiated patients. Eleven patients, with atrophy and telangiectasia after radiotherapy to the skin to a high dose, were found to have no functional eccrine glands by this technique. A range of results from normal numbers of eccrine glands through partial and, rarely, complete loss was observed in patients given lower doses and in whom the skin was visually normal. When the irradiated side outside the boost area in 16 breast cancer patients who received postoperative radiotherapy was compared to an equivalent area on the untreated, contralateral side, 11 showed a greater than 50% reduction in the density of functional eccrine glands. The method appears to be a sensitive, quantitative assay for a permanent change in skin and so ought to facilitate meaningful comparison of different regimens of radiotherapy. Further studies are required to determine the dose-response relationship, latency and progression of the observed changes.


Radiotherapy treatment planning of basal meningiomas: improved tumor localization by correlation of CT and MR imaging data.

A localization technique, based on three-dimensional CT and MR imaging data for precision radiotherapy of basal meningiomas, is presented. Indications for radiotherapy included unresected tumors, gross disease remaining despite surgery, and recurrences. The patient's head was fixed in a stereotactic localization system which is usable at the CT, MR and the linear accelerator installations. The geometrical distortion of MR imaging data was evaluated in three dimensions by phantom measurements. The geometrical distortion was "corrected" (reducing displacements to the size of a pixel) by calculations based on modelling the distortion as a fourth order two-dimensional polynomial. The target volume was defined in three-dimensional MR imaging data after application of 0.1 mmol/kg b.w. Gd-DTPA solution and transferred precisely from MR onto CT data to provide a map of the radiation attenuation coefficient for dose calculation. The superior soft tissue contrast of MR showed an excellent tumor delineation especially when the bony base of the skull obscured the target in CT images. Target volume, calculated dose distribution, and critical structures could be transferred between CT and MR imaging data and displayed as three-dimensional shaded structures for better assessment for matching of target volume and dose distribution. With the described planning system a more precise target definition of basal meningiomas was possible by integration of the superior tumor delineation in MR compared with CT.


"PCL" a new automatic fast reader suitable for in vivo dosimetry.

The authors present a new automatic TLD reader specially designed for medical dosimetric applications, which allow considerable time-saving. The "PCL" reader is based on an isothermal heating kinetics and can be used with TL material of any nature and any shape (powder, microrods, pellets). Doses from 1 microGy to 10 Gy can be measured, or higher doses by interposing an optical absorber in front of the PM. The readout system is controlled by an IBM compatible personal computer. Results can be printed under the form defined by the users and then can be straightly stored in a patient sheet or an experience book. Tests performed with LiF chips TLD 100 and 700 (HARSHAW), Li2B4O7:Mn discs LiB (ALNOR), LiF powder PTL 717 (DESMARQUET) and Li2B4O7:Cu powder (CEN-FAR) are presented. They show a good reproducibility and interesting dosimetric properties.


Are port films reliable for in vivo exit dose measurements?

The possibility of using conventional port films as an in vivo method for obtaining relative exit dose distribution in patients is evaluated. Kodak "Verification" films in "Localization" cassettes are positioned in the usual clinical conditions behind an homogeneous polystyrene phantom as well as behind a phantom containing air, wood and aluminium inhomogeneities. Taking beam divergency into account the densitometric profiles are projected back to the exit side of the phantom. They are compared to the profiles obtained with an ionization chamber used under full backscatter conditions. The agreement between the off-axis ratios determined with either method are mostly better than 2% and never exceed 5%. These phantom measurements are completed by a comparison between off-axis ratios determined on a port film for a head and neck patient and those obtained by diode dosimetry applied on the patient at the exit side of the beam. A similar agreement as between film and ion chamber on the phantoms is obtained. These encouraging results illustrate the possibilities of using conventional port films for in vivo dosimetry.


The treatment of resistant neuroblastoma with 131I-mIBG: alternative methods of dose prescription.

A UK multi-centre study has been carried out to collect medical and dosimetry data from treatments with 131I-metaiodobenzylguanidine (mIBG) for patients suffering from resistant neuroblastoma. All data have been acquired in a standardised way, following strict physics and clinical protocols. The accuracy of three different methods of dose prescription was studied. The results show that the most accurate method involved the use of an initial tracer study to determine the therapeutic activity required to deliver a predetermined absorbed whole-body (WB) dose.


Glycidyloxy compounds used in epoxy resin systems: a toxicology review.

The glycidyloxy compounds constitute an important group of chemicals used extensively in the formulation of epoxy resin systems employed in coatings, electronics, structural composites, and adhesives. Although extensive toxicological data are available on glycidyloxy compounds, use and understanding of the data have been hampered by two major problems: (1) proper identification and complexity of the epoxy systems in question, and (2) absence of meaningful classification of epoxy materials. This paper provides a classification scheme with CAS numbers and reviews the mammalian toxicology of the most common glycidyloxy derivatives used in epoxy resin systems based on both published and proprietary information. Although the toxicity of many of the glycidyloxy compounds used in epoxy resin systems can be characterized as low, the diversity of compounds found within this group precludes broad generalizations for the class. This comprehensive account should facilitate a clearer understanding of the potential health effects and allow for easier comparison among compounds containing the glycidyloxy moiety.


Cancer risk assessment: the science that is not.

Regulators have adopted the assumption of low dose linearity in cancer risk assessment, variously justified as scientifically correct and as responsible public health policy. Corollary assumptions are the one-molecule-one-hit hypothesis, the exclusion of no-effect thresholds, and the equivalency of response in experimental rodents and man. While our understanding of the carcinogenesis process remains tentative, these generalizations are not sustained by the limited scientific evidence available, not even as interim working hypotheses. In this light, they reflect a facile bureaucratic response to pragmatic demands borne of political perceptions, rather than the recognition of a complex and still opaque reality.


Relationship between the shape of dose-response curves and background tumor rates.

Various authors have argued that a chemical which augments a carcinogenic process, which is already producing tumors spontaneously, will produce an increase in tumors no matter how small the dose. For this situation, no threshold dose exists whether or not the chemical is genotoxic. Under such conditions, it is expected that the dose-response will contain a linear term. A large database of animal bioassays (Gold et al., 1984) was examined to study the relationship between the shape of dose-response curves and the background tumor rate. The multistage model was fit to 143 data sets from 75 different chemicals. As expected, the presence of the linear term was correlated with the background tumor rate and the presence of higher degree terms in dose (cubic or greater) decreased as the background rate increased. This examination of a large number of chronic bioassay results appears to support the premise that low dose linearity is generally expected for tumor sites where background tumors occur, even for carcinogens which were negative by the Salmonella genotoxicity test.


A proposed approach to regulating contaminated soil: identify safe concentrations for seven of the most frequently encountered exposure scenarios.

Since 1980, more than 10,000 sites in the United States have been shown to contain soil which has elevated concentrations of various xenobiotics. Since that time, guidelines for deciding whether the level of contamination is worthy of concern have been proposed or promulgated by dozens of local, state, and federal regulatory agencies. Unfortunately, there has been little consistency in the guidelines suggested for each soil contaminant. For example, (a) the basis or rationale for some of the cleanup levels is unclear, (b) approaches to setting cleanup levels vary between states and agencies, (c) cleanup objectives often vary among agencies within the same state, and (d) the cleanup levels are usually set in a scientifically haphazard manner. This paper proposes that the most cost-effective and efficient way to quickly regulate contaminated soil is to establish "safe" concentrations for each chemical for the seven most common exposure scenarios. These exposure scenarios include (1) residential, (2) industrial, (3) agricultural, (4) recreational, (5) groundwater, (6) wildlife and aquatic species, and (7) runoff/erosion of particulates to waterways. The scientific approach and rationale for calculating the cleanup criteria are illustrated by evaluating dioxin and benzene, toluene, and xylene (BTX). The methods suggested here indicate that levels of dioxin of 25 and 50 ppb in residential and industrial soils, respectively, should be acceptable. The predominant concern for the agricultural and recreational scenarios is the runoff of particulates to waterways. For BTX, benzene will dictate the degree of cleanup and the primary hazard at most residential sites will be the inhalation of vapors. Benzene concentrations of 2.5, 14, and 250 ppm should be acceptable for residential, industrial, and recreational soils, respectively. Depending on the depth to groundwater and aquifer use, protection of groundwater may be the driving concern for establishing BTX cleanup levels and must be determined using site-specific factors.


On the carcinogenicity of cadmium by the oral route.

Cadmium and cadmium compounds are carcinogenic both by inhalation and by injection. For purposes of risk assessment, a prudent public health approach has been that, if a chemical has been demonstrated to be carcinogenic by one route, it should be considered carcinogenic by all routes. This policy has been questioned for several toxic metals including cadmium. After reviewing the literature on cadmium carcinogenicity and genotoxicity, we think that cadmium should be considered noncarcinogenic by the oral route. The bases for this decision included: (1) a database for genotoxicity of cadmium with more negative test results than positive results and with most positive results in in vitro tests, indicating that cadmium has limited genotoxicity; (2) some epidemiologic evidence of respiratory tract cancer and prostatic cancer in people occupationally exposed to airborne cadmium but no reliable evidence of gastrointestinal tract cancers in workers; and (3) a large dietary oncogenicity study in rats of cadmium chloride at several dose levels, including a maximally tolerated dose (50 ppm) in males, which showed no increase of tumors due to cadmium ingestion in all of the 19 tissues examined. The conclusion that an agent, which has been shown to be carcinogenic by one route of exposure, is not carcinogenic by a second route should be made only in the presence of robust data which indicate the lack of effect via the second route of exposure.


An abbreviated repeat dose and reproductive/developmental toxicity test for high production volume chemicals.

A novel protocol is described for obtaining preliminary data on repeated dose systemic effects and reproductive/developmental toxicity. The test protocol was developed by a group of experts at the request of the U.S. Environmental Protection Agency (EPA) for use as part of a Screening Information Data Set on high production volume chemicals. Interest in this protocol is shared by several regulatory agencies, including the Organization for Economic Cooperation, the European Community, and the EPA. To validate the study protocol, ethylene glycol monomethyl ether (EGME) was used. After a dosing period of approximately 6 weeks, EGME showed both systemic and reproductive/developmental effects similar to those previously reported using standard protocols. Thus, this test protocol may be used as a screening tool for high production volume chemicals.


Rising cancer mortality in the United States, 1962-1987: evidence against environmental causation.

The recorded rise in cancer mortality, particularly in industrialized nations such as the United States, is often attributed to increasing environmental carcinogens and has resulted in the public expectation for increased regulation. However, longitudinal Gompertzian analysis indicates that the major factor for rising cancer mortality is the increasing deterministic competitiveness of cancer in a climate that is becoming more conducive to human survival. Hence, rising cancer mortality is a predictable manifestation of a natural relationship between human aging and mortality, and should not be interpreted as evidence of increased environmental carcinogens.


Exposure to airborne asbestos in buildings.

The concentration of airborne asbestos in buildings and its implication for the health of building occupants is a major public health issue. A total of 2892 air samples from 315 public, commercial, residential, school, and university buildings has been analyzed by transmission electron microscopy. The buildings that were surveyed were the subject of litigation related to suits alleging the general building occupants were exposed to a potential health hazard as a result of exposure to the presence of asbestos containing materials (ACM). The average concentration of all asbestos structures was 0.02 structures/ml (s/ml) and the average concentration of asbestos greater than or equal to 5 microns long was 0.00013 fibers/ml (f/ml). The concentration of asbestos was higher in schools than in other buildings. In 48% of indoor samples and 75% of outdoor samples, no asbestos fibers were detected. The observed airborne concentration in 74% of the indoor samples and 96% of the outdoor samples is below the Asbestos Hazard Emergency Response Act clearance level of 0.01 s/ml. Finally, using those fibers which could be seen optically, all indoor samples and all outdoor samples are below the Occupational Safety and Health Administration permissible exposure level of 0.1 f/ml for fibers greater than or equal to 5 microns in length. These results provide substantive verification of the findings of the U.S. Environmental Protection Agency public building study which found very low ambient concentrations of asbestos fibers in buildings with ACM, irrespective of the condition of the material in the buildings.


[Synchrotron radiation: a new source in x-ray mammography].

This work was aimed at evaluating the image quality obtainable in X-ray mammography using synchrotron radiation monochromatic lines. After a short review of the current mammographic techniques, the main features of synchroton radiation in the X-ray field are analyzed, especially of that emitted by the Adone storage ring. Its features are then compared with the radiation emitted by a Coolidge tube. The experimental unit used in this study, including beamline, monochromator and mammograph, is then described together with the experimental method for carrying out a series of experiments in the mammographic field employing both monochromatic lines (E = 17 keV) and white radiation from conventional sources. The first series of experiments is described, which employed standard phantoms: the dependence of resolution and contrast on both wavelength and thickness of breast specimens is reported. Several mammograms of neoplastic breast specimens were obtained after mastectomy: they were acquired using both synchrotron monochromatic lines and radiation emitted by a conventional tube and employing the same acquisition system. The comparison of the two series of images shows that synchrotron radiation can demonstrate a high number of anatomopathologic details with high definition, contrast and resolution which cannot be obtained by means of a conventional source. Our results appear very promising and suggest synchrotron radiation as the major tool in the early diagnosis of neoplastic breast lesions.


[Image perception and interpretation in senology. The relationship between the clinical picture, radiological sign and histology].

Once more, the authors are confronted with the difficult interpretation of senological images. When reviewing the radiologic features of a series including the symptomatic, the asymptomatic and the male breasts, the goal is to relate the patterns to clinical and histologic findings in order to improve the perception of the radiologist himself in transferring and integrating the information. The final conclusions, after reviewing the images, are: a) for the correct interpretation of senological images, the sign must be correlated with clinical findings and with data from other modalities; b) the radiologist's attitude must be always investigative and never exhaustive, due to the variability of all factors, which sometimes make a judgement of "radiological tranquility" in the breast impossible; c) the radiologist must, nowadays, improve his perception of senological images, thus becoming the one who knows how to correlate clinics to the images. By increasing his perception, his interpretation capabilities will certainly increase too.


[A multicenter study for the evaluation of the diagnostic efficiency of mammography and echography in nonpalpable breast neoplasms].

The Breast Section of the Italian Society of Radiology set up a cooperative study which included 17 Departments of Radiology and Breast Diagnosis in order to evaluate the diagnostic accuracy of US versus mammography in nonpalpable breast lesions. From January 1, 1989 to december 31, 1990, 400 nonpalpable breast lesions (142 benign lesions, 59 in situ and 199 infiltrating carcinomas) were detected by mammography and/or US; they had questionable/suspicious findings which called for further investigation by means of cytology and/or histology. US proved much less sensitive in non-palpable carcinomas than mammography (49.2% vs 93.8%), also in younger women, and failed to detect 50% of the benign/malignant nonpalpable lesions identified by mammography. US sensitivity was directly related to lesion diameter and probe frequency: 38.7% in infiltrating carcinomas < or = 5 mm vs 56.8% in those > 10 mm; 12% in the patients examined with a 5-MHz probe vs 57.7% in those examined with a > or = 7.5-MHz probe. Furthermore, the most significant US patterns of nonpalpable lesion were irregular contours, posterior attenuation and irregular internal echoes, while an irregular skin line and Cooper ligaments had no significant relation with carcinoma. Thus, breast US cannot be used as a screening test on asymptomatic patients not even on young women with radiologically dense breasts. On the contrary, US performed with high-frequency probes is useful in the assessment of nonpalpable lesions identified by mammography, and allows, in many cases, US-guided cytology and preoperative localization.


[The diagnostic imaging of complex breast nodules].

This study was aimed at determining the role of high-frequency (7.5 MHz) US combined with cytology in the diagnosis of complex breast nodules (complex cysts--cystic tumors). The study population included 60 patients presenting with complex breast nodules selected on the basis of US patterns among 3,000 cases. All patients were also submitted to US-guided fine-needle aspiration biopsy (FNAB). Cytology of nipple discharge was always performed when discharge was present (15 cases), mammography was performed in 50 cases and pneumocystography in 10. US allowed the identification of the lesion in all patients and the diagnosis of nature in 73%; with FNAB the figure reached 96.7%. Mammography identified the lesion in 95% of patients, but failed to reveal the complex nature of the nodule. In a small number of cases mammography proved to be a useful complementary tool demonstrating malignant features not recognizable on US images. On the contrary, pneumocystography yielded no further information with respect to US. Diagnostic control was obtained by means of surgery in 30 patients and of clinical-US follow-up in the extant 30 cases. On the basis of their US features the lesions were classified into two groups: I) nodules having a mainly liquid component--i.e., hemorrhagic, septic, multilocular cysts, papillary cystadenoma; II) nodules having a mainly solid component--i.e., solitary intraductal papilloma, intracystic carcinoma, mixed carcinoma, phylloid adenoma, sarcoma. As to the former group, US proved reliable in making a diagnosis in the cases with typical hemorrhagic, septic and multilocular cysts. In the atypical cases, FNAB of the solid component of the nodule was necessary to differentiate irregular clots, thick septa or inflammatory thickening from different conditions. As to the latter group, FNAB of the solid component and/or mammography proved useful in making a diagnosis, even though to this aim US revealed peculiar patterns which were highly suggestive. In our experience, combined US and FNAB are of basic importance in the diagnosis of breast lesions, thus replacing pneumocystography which has been widely employed so far. As regards mammography, its role seems limited to pointing out the peculiar characters of malignancy which could not be demonstrated otherwise.


[A comparison between echography and computed tomography in assessing neoplastic recurrences in superficial soft tissues].

Thirty-seven superficial soft-tissue recurrences were evaluated with ultrasonography (US) and computed tomography (CT) to assess the correct diagnostic approach. US and CT examinations were performed at the same time. High-frequency US probes and a third-generation CT scanner were employed; all the lesions underwent also histology or cytology. US correctly identified as recurrences or fibrous tissue all the 37 lesions, whereas CT diagnosed 30 lesions only. Seven of the 14 recurrences < 2 cm diameter were not demonstrated. In conclusion, US provides more reliable information than CT relative to small lesions, which suggests that US must be performed just after therapy. Nevertheless, when bone involvement is suspected, CT is required and its use is also suggested to monitor distant metastases.


[Contrast media in echography].

In medical US, the use of specific contrast media to increase the echogenicity of structures and organs changes their absorption of the US beam, and modifies the through-transmission velocity. This can be of great diagnostic value. Contrast media can help depict vessels and cavities, increase the sensitivity of Doppler examination, and make the differentiation of normal and pathologic tissues easier. The products which are currently available do not completely fulfill the needs of clinical researchers. The first papers reporting on some clinical applications of these contrast media in humans are now appearing in literature. Contrast media for diagnostic US can be classified in five groups: 1) free gas bubbles; 2) stabilized gas bubbles; 3) colloidal suspensions; 4) emulsions; 5) aqueous solutions. These agents are quite different, as to both chemical and physical features and distribution within living tissues. Different clinical applications are thus possible for each of them; a unique contrast medium which will meet all the needs of the various clinical situations seems inconceivable at present. Most probably, a variety of products will develop, each with its own application field; in clinical practice, it seems likely that different products will be used, according to the specific clinical needs.


[Digital radiology with storage phosphors in cephalometric study in orthodontics].

Conventional radiology is continually modified with the development of digital systems which can be used for several types of radiologic examinations. Our study was aimed at evaluating the advantages of these new technologies in the orthodontic field, where the problems associated with image quality and radiation protection are major especially in young patients; the latter goal is achievable by dramatically reducing radiation dose and by avoiding repeating the exam. In our study, we compared lateral teleradiographs of the skull for cephalometric analysis obtained using conventional and digital diagnostic methods. The preliminary results demonstrated that the two imaging techniques did not differ relative to bone structure representation, even though the digital system provided better visualization of soft tissue structures. Computed radiography also allowed a marked reduction in the number of repeats and reduced radiation dose. The current disadvantages of this imaging method are the high initial cost of the equipment, reduced work rate, and the need of frequent technical assistance.


[Destructive spondylopathy in the dialysis patient. The diagnostic role of magnetic resonance].

Magnetic resonance imaging (MRI) was employed to study 7 long-term hemodialysis patients affected with destructive amyloid spondyloarthropathy. In the appropriate clinical setting, MRI proved to be more useful than conventional radiography or CT and more definitive in excluding infections. Indeed, MRI can replace more invasive procedures in making the correct diagnosis. Different than what is reported in literature, a high incidence of odontoid lesions (C2) was observed in our series, with extraosseous and extradural deposits of soft tissue masses (amyloid pseudotumors), subluxation, odontoid invagination and medullary compression. Bone lesions, involved disks and amyloid pseudotumors typically exhibited low-intensity signal on both T1- and T2-weighted sequences and no enhancement following Gd-DTPA injection. The use of MRI is thus suggested, especially at cervical level, also in case of relatively mild symptoms.


[Psoriasis arthropathica. A review of the literature, general considerations and the authors' personal experience].

A retrospective study has been carried out on 897 psoriatic patients in order to verify the incidence and radiological patterns of psoriatic arthropathy (PA). Site of involved joints, appearance and degree of involvement were correlated with extent of skin disease and blood test results. Sixty-five patients (7%) showed "clinical" arthritis whereas only 20 cases (2.2%) were radiologically positive; among them, 35% were classified as "severe" forms. Peripheral arthritis was observed in all cases, involving the hand in 85% of patients. The distal interphalangeal joints were the most affected location in the feet (78%) and the proximal interphalangeal joints in the hands (94%). The extant small peripheral joints were involved in decreasing rates proceeding proximally. Bilateral and asymmetric involvement was observed in most of the patients; hypertrophic interphalangeal joints erosion was the typical pattern in 100% of cases, evolving in rheumatoid-like ankylosis in 23% of them. Spondylitis and/or sacroiliitis were associated in 50% of patients. No correlation between degree of arthritis and skin disease was found in our series, with the exception of proximal and axial joints arthritis, in which extensive skin disease and severe small joints involvement were associated in 80% of cases. Clear differential features were demonstrated between peripheral PA and rheumatoid arthritis, and between spinal involvement in PA and ankylosing spondylitis. Poor correlation of distal arthritis to psoriatic nail involvement was also demonstrated.


[The treatment of acute cholecystitis by percutaneous cholecystostomy].

The authors report on their personal experience with percutaneous cholecystostomy (PC) in 36 cases of acute cholecystitis (AC). PC was successful in 34 cases, improving the clinical condition of the patients within the first hour following treatment and normalizing the laboratory data within 24-48 hours. Twenty-seven patients with calculous AC underwent cholecystectomy within 4-15 days. In 6 cases (3 calculous and 3 acalculous ACs) PC was the only treatment performed; in one case (calculous AC) PC was combined with lithotomy, the stone fragments being extracted via the cholecystostomy. According to literature reports, to date PC has been performed mainly--as an alternative to surgical cholecystostomy--on the patients unsuitable for cholecystectomy due to their age or to severe impairment of their conditions. In our experience, the procedure can be performed on a wider range of patients as a final (notably in acalculous AC) or temporary step (notably in calculous AC where it may allow cholecystectomy to be delayed and thus performed under better clinical conditions, with decreased morbidity and mortality risks).


[Biliodigestive anastomoses on echography. The normal and pathological aspects].

The normal and pathological US features of different types of bilioenterostomy (hepaticojejunostomy, choledochoduodenostomy, polyductal bilioenteric anastomosis) are described, as observed in a prospective study of 27 patients, for a total number of 35 (18 normal and 17 abnormal) examinations. For 20 patients with hepaticojejunostomy, the bilioenteric anastomosis was identified on 13/13 normal examinations and 10/12 pathological examinations. For 2 patients with choledochoduodenostomy, the bilioenteric anastomosis was identified on 2/2 examinations. For 5 patients with polyductal bilioenteric anastomosis (each patient having 2 or 3 anastomoses), all surgical anastomoses were separately identified on 6/8 examinations; as for the remaining 2 patients, 2/3 and 1/3 anastomoses were seen. An abnormal condition was correctly recognized in all the 11 patients with local disease (lithiasis and benign biliary stricture, 2 patients; benign biliary stricture, 5 patients; primary cholangiocarcinoma, 1 patient; recurrent malignancy, 3 patients); in 1 patient, parenchymal and biliary abnormalities due to vascular obstruction were misinterpreted as a result of benign stricture. US can demonstrate the surgical anastomoses between the resected common bile duct or second order intrahepatic ducts and the jejunal loop, with typical features according to the type of surgery performed. Knowledge of such normal appearances after bilioenteric surgery is mandatory in order to detect and correctly evaluate such possible abnormalities at this site as lithiasis and benign or malignant strictures.


[The experience of diagnostic and therapeutic integration in rectal cancer. Preliminary notes].

In our University, many different radiosurgical options are available to treat rectal carcinoma. Selecting the patients to submit to treatment requires accurate clinical and radiological staging. A team of radiologists, radiotherapists, surgeons, endoscopists and pathologists has been created to stage the patients and to follow the final results. The team have decided the diagnostic and therapeutic protocols. The patients with rectal cancer undergo radiotherapy after staging and are subsequently restaged. If indicated, surgery is performed and histology is compared with restaging, to assess the accuracy of the diagnostic procedures. All diagnostic and therapeutic decisions are made collectively by the team, during scheduled meetings. All data are stored in a computer program. This paper deals with the working method we used, its advantages and the outcome of the first 23 studied patients. Restaging was compared with histology: transrectal US (performed in 8 patients) showed 100% accuracy in evaluating local tumor spread (T). CT had 91% accuracy in defining T and 60% accuracy in N, with a tendency to overstaging. In 78% of patients > 50% reduction of tumor size was observed and the distance from the anal canal increased in 95.5%. This study will provide the overall accuracy of the clinico-radiologic staging, the survival rates and the indication of prognostic signs.


[The anatomical assessment of the renal fascia in the normal subject by using computed tomographic equipment with advanced technology].

One hundred patients, affected with diseases not involving the peri-renal and pararenal spaces, have been examined in order to evaluate the visibility of the renal fasciae, using a CT scanner provided with high spatial and contrast resolution. The anterior renal fascia has been recognized in 71% of cases on the right side and in 88% on the left. The posterior renal fascia had 96% of positive bilateral detectability. The latero-conal fascia was detected in 83% of cases on the right and in 91% on the left. The inter-renal fascia was recognized in 25% of cases, at the pancreas or, more frequently, on caudal planes. The peri-renal septa were seen in 58% of cases, mainly on the left side. Compared to previous data reported by other authors, the visibility of the renal fasciae has been increased by the greater spatial and contrast resolution offered by the new CT scanner, thus allowing better anatomical evaluation of peri and para-renal spaces.


[The stenotic-occlusive anatomy and pathology of the renal arteries. Their evaluation by magnetic resonance angiography].

Magnetic resonance angiography of the renal arteries was performed in 10 healthy subjects, 10 patients with renal artery stenosis and 2 patients with accessory renal artery (1 unilateral, 1 bilateral). All patients selected among 35 subjects with suspected renovascular hypertension had previously undergone digital subtraction angiography. Four patients were studied before and after percutaneous transluminal angioplasty. MRA was performed with time-of-flight technique, with 2D and 3D FISP and 2D FLASH gradient-echo sequences. Digital subtraction angiography demonstrated stenoses ranging 40% to 90% in 10 cases, 7 unilateral (1 transplanted kidney) and 3 bilateral. RA correctly depicted > 90% stenoses in 5 cases, between 50% and 90% stenoses in 2 cases and < 50% in 2 cases. Four stenoses were not properly graded (3 over-graded and 1 not visualized because distal to ostium). Diagnostic accuracy was 71% for unilateral stenoses and 66% for bilateral stenoses (overall accuracy 69.2%).


[Percutaneous transluminal renal angioplasty of the solitary kidney].

We report on our experience with percutaneous transluminal angioplasty (PTA) of the renal artery in solitary kidney patients. PTA was performed on 31 subjects (mean age: 52 years): 7 had a solitary kidney because of nephrectomy and 24 had a solitary functioning kidney. Patients were selected with clinical and laboratory examinations first and then with angiography. PTA was employed to treat renal artery stenoses 60%-95% of the whole arterial lumen. The procedure has been considered technically successful in 29 cases, with 77%-33% reduction of the mean amount of stenosis. As to the clinical evaluation of the results, blood pressure and creatinine values variations were considered. Of the 25 patients on follow-up, 13 appeared to be treated (52%), 8 improved (32%) and 4 unchanged (18%). On the whole, we observed 5 complications (2 hematomas at the approach site, 1 intimal dissection and 2 segmental infarcts), with a 23.4% rate comparable with PTA complications in non-solitary kidney patients. The good revascularization, the reduction in blood pressure values, the very small percentage of complications point to PTA of the renal artery as the procedure of choice in solitary kidney patients.


[An evaluation of the N parameter according to the system of the American Thoracic Society (ATS) in pulmonary carcinoma. A comparison between radiology, surgery and histological diagnosis].

The hilar and mediastinal lymph nodes of 36 patients with bronchogenic carcinoma were evaluated with computed tomography (CT). The American Thoracic Society (ATS) mapping was employed, which defines nodal stations in terms of well-recognized anatomic landmarks which are easily identified with CT and during thoracotomy. The differences (30 cases) between CT and surgical measurements in the 124 nodal stations which could be analyzed are discussed in detail. A better correlation was found using a 2-cm threshold value to define a "positive" or "negative" lymph node with CT. The comparison of radiologic data and the presence of metastases showed how with the 2-cm size criterion sensitivity drops from 81% to 53%, whereas specificity rises from 53% to 84%, thus affecting the subsequent diagnosis and therapy positively.


[Dosimetric problems and their solution in the preparation of a 6-dual-field total-skin technique].

The six-field total skin electron irradiation (TSEI) technique needs an accurate preliminary dosimetric study. The American Association Physics in Medicine (AAPM) defined a dosimetric protocol that recommends the careful dosimetry of the horizontal, the dual and the six-dual fields by using both a cubic and a cylindrical phantoms. In our Institute, in a TSEI development program, we carried out the preliminary dosimetry according to AAPM criteria. We also investigated some dosimetric problems--e.g., the so-called "cable effect", which takes place when the detector cable in a TSEI field is not well shielded, polarity effects and photon contamination. As to the "cable effect", it is especially marked with the Markus NE2534 chamber; moreover, this effect, if not considered, can lead to overestimation of X-rays contamination.


[Conformal technics by the movement of bars in pendular fields. 1. Prototype realization and the possible applications].

The growing interest for conformal radiotherapy originates from the need of giving the prescribed dose to the target volume, by sparing, at the same time, surrounding healthy tissues and organs. More dose to the target volume with respect to the healthy tissues always increases the curative possibilities of the treatment. However, the development of conformal techniques implies an increased complexity of the treatment and the solution of many technical and dosimetric problems. In our Institute we are developing new conformal techniques, based on the use of moving bars driven by a computer-controlled system in arc therapy. This paper refers to the conclusion of the preliminary part of our work: a movement (translating or rotating) of bars in arc therapy seems to have good chances to tailor dose distribution in a relatively simple way. We realized two mechanical systems driven by computer for translating and rotating movements of a bar. The two techniques have been tested by TLD and film dosimetry on acrylic phantoms. We present the results of these tests, and describe technical problems and the clinical possibilities of this method.


[Conformal technics by the movement of bars in pendular fields. 2. The dosimetric aspects].

The development of conformal techniques by movement of bars in pendular fields requires a careful examination of many physical and dosimetric problems: bar-critical organ synchronization problems, dose calculation problems, and problems relative to the "shadow effect". The use of a bar in an arc field, causes to a slow gradient of dose between shielded zone and target volume with a loss of homogeneity in dose distribution. This effect is well known ("shadow effect") and depends on the fact that different points spend different times beyond the bar's shadow. In this work the problem is investigated in the case of moving bar technique, mainly for dose calculation possibilities; then the possibility is analyzed of optimizing dose distribution by means of filters whose profile can be calculated for simple geometric conditions (fixed bar on the isocenter without considering the profile of the patient). These filters will be made in our Institute and they will be tested in various conditions, for both fixed bars and moving bars in arc fields.


Assessing human exposures to pesticides.

Pesticide use is inevitably associated with chemical exposures that range from inferred nondetectable levels to easily measurable ones using sensitive, readily available analytical tools. Whether these exposures are of any biological significance is determined by duration, dose, and biological reactivity. The overwhelming majority of human exposures occur in a diverse chemical milieu of a nutritive substances and are of no known significance. Technologies that minimize human chemical exposures and maximize pesticide effectiveness are favored. The risk characterization process is ideally suited to assist decision makers concerning the protection of human health and evaluation of agricultural tools. It is the best means available to balance the review of pesticide impacts on health and agriculture. Regulators must be cautious to acknowledge the relative rather than absolute nature of the risk characterization process. Workplace biological monitoring must become more commonplace as a means to evaluate the chemical exposure potential of various work tasks and greater attention must be given to the biological validation of methods. Earlier needs for data to develop workplace hygiene strategies have been replaced in recent years by demands of the risk assessment process, which utilizes direct estimates of exposure and absorbed dose. Animal models, no matter how attractive, are not presently a substitute for human experience. Opportunities to gather more information on human experience associated with pesticide exposures must be more aggressively identified and pursued. Only a very small time lag should exist between identification of pesticide metabolites in rats and evaluation of metabolic similarities in humans. At the present levels of analytical sensitivity, most of our current uncertainty about the extent of worker exposure and patterns of metabolism between species can be at least clarified with the cooperation of persons who are exposed during normal day-to-day activities in the workplace. Only with better human data will the risk assessment process warrant greater reliance in decision making concerning our chemical exposures and human experience.


Biomarkers of pesticide exposure.

Incorporation of biomarkers in studies of occupational exposure hazards is now recognized as a highly useful adjunct to the surrogate measures employed in the past, for example, time worked, ambient air data, interview responses. Application to studies of workers potentially exposed to pesticides has barely begun and provides many challenges to chemist/epidemiologist teams. This review indicates several excellent studies employing multiple-exposure measures to document the validity of specific biomarkers for particular exposure situations. In general, exposure reflected by urinary assays of specific pesticides is a low percentage of that indicated by dermal or breathing zone measures. Markers for many of the pesticides in current usage have yet to be developed and validated, and information on population variability is generally lacking for existing markers. The challenge provided by the complexity of multiple, and often unknown, exposures to individuals in pesticide environments has begun to be addressed employing cytogenetic or urinary measures that attempt to integrate these complex exposures. The lack of data regarding sensitivity and specificity of biomarkers, especially in complex exposure situations, is a major problem that perhaps will best be addressed by studies combining nonspecific measures with specific ones, utilizing stored sample banks created for that purpose. Expanding the repertoire of available biomarkers of pesticide exposure and employing multiple ones in well-designed study protocols will provide critical tools in the evaluation of pesticide safety and design of appropriate measures to minimize adverse exposures. Ironically, one of the problems that biological markers of exposure can help overcome, reliance on poorly measured ambient exposure data, hampers the evaluation of the markers themselves. Therefore, the combination of in vitro, animal, and human data will give the best picture of a marker's performance. (Wilcosky 1990).


Estimating worker exposure for pesticide registration.

For the registration procedures of pesticides, the level of exposure during the various activities in which pesticides are handled has to be estimated. Different worker exposure models have been put forward in Europe and North America. These models are discussed and compared to each other for their output in terms of estimated levels of potential inhalation and dermal exposure. It is concluded that the output varies with the model, largely for two reasons. First, the underlying databases are completely different, which is inherent to locally different equipment and farm sizes. Second, the statistic used in the estimation of a level of exposure from a database varies from a geometric mean to the 90-percentile. The estimated levels of exposure may be used in a first step of the risk assessment. It is recommended that the relevant parts of all four models be considered to increase the representativity of the predicted level of exposure.


Blood esterase determinations as markers of exposure.

The bases of using blood enzyme activity measurements [e.g. AChE, non-specific cholinesterase (BChE), carboxylesterase] as markers of organophosphate ester (OP) exposure are inhibition of activity by the binding of OPs to serine active sites in the enzymes, and the accessibility of the enzymes in RBCs and serum. The methods used to determine esterases in the blood of humans, experimental animals, and wildlife are outlined with emphasis on the acetylcholinesterase (AChE) of the red blood cell. Adaptations of an acetylthiocholine ester assay of Ellman et al. (1961) are common, but other colorimetric procedures, radiometric assays, and pH methods are also in use. Optimized, standardized methods are needed to assess exposures and provide a solid basis for risk assessment analyses. Useful adjuncts to ChE measurements are oxime reactivation tests and assay of neuropathy target esterase, an enzyme associated with organophosphate-induced delayed neuropathy. Determination of urinary metabolites compliments, but does not substitute for, the information obtained from blood ChE studies. Future assays are likely to involve antibodies to OP-protein complexes. Improvements in techniques permit the detection of small decreases in ChE activities. Whether or not such small decreases in ChE activities can, by themselves, constitute an adverse effect for input into risk assessment analyses is a controversial matter.


Reentry field data and conclusions.

A review of the reported foliar residue data has revealed a number of deficiencies in the reentry intervals currently regulated, in particular, by the EPA and some by California. Deficiencies were also identified in the available information necessary to recommend better reentry intervals. Information regarding the frequency of exposure for individual or groups of harvesters is the most fundamental deficiency. It is needed to define a more realistic chronic criterion of allowable daily cholinesterase inhibition without cumulative symptoms. The second criterion of preventing acute overexposure is more readily defined. For the purposes of this study, the criteria of 4% mean daily inhibition and 50% acute inhibition were chosen as acceptable. Based on these criteria, the available data, and by using the unified field model assessment as the basis for comparison (Table 9), EPA reentry intervals for nine insecticides in Table 4 appear inadequate (i.e., not within the range of the model recommendations); 10 are adequate; and only one appears excessive as summarized in Table 10. A similar comparison of California's reentry intervals indicates only two may be inadequate or marginal; 13 are adequate; and five may be excessive. Although these conclusions are based on a considerable amount of residue data, the data are not equally distributed among all pesticides nor has the model been confirmed in all the cropping and harvest conditions examined. However, the model has been developed under realistic field tests, most of its premises have been confirmed in a limited number of tests, and its simulated predictions appear to parallel experience in California where pesticide use and decay conditions may have been most severe but recently well scrutinized. The model's recommendations largely substantiate the regulations developed in California. However, its conclusions definitely suggest that improved levels of protection are needed in other regions. Future reentry intervals will require more comprehensive residue data. The toxicities of detectable metabolites for a few insecticides will need to be determined. More crop residue dosing coefficients are also needed for manually harvested crops. These data must be interpreted in terms of the potential both for acute poisoning from variable residues and for chronic poisoning from repeated exposure to more consistent residues. Surveys of the temporal exposure patterns of harvesters or crews of harvesters are vital to assess the cumulative effects and set the most appropriate chronic cholinesterase response limits. While we await further data, there is sufficient information now to justify longer reentry intervals to protect harvesters nationally.


Pesticide protective clothing.

In looking into future directions of "protective clothing" for pesticide users, the final EPA ruling scheduled for release in June 1992 (Smith personal communication) places the majority of its recommendations on the label. Therefore, it will be up to pesticide manufacturers to provide protective clothing information on their products labels. Research on protective clothing continues to show variations due to fabric characteristics of fiber content, fabric construction and finish. These variabilities are compounded by variation s due to pesticide formulation and pesticide chemical and are further compounded by field studies vs laboratory simulations. With hundreds of fabric variations compounded by the thousands of chemical compounds and formulation variations, the consumer cannot be expected to make proper decisions regarding protective clothing. The user of the product does not have the knowledge to select the appropriate clothing. Manufacturers must supply this information, but they must also have data to support recommendations of their clothing for pesticide protection. This shifts the responsibility for recommending adequate protective clothing, as well as the concern for product liability, to the manufacturer.


Exposure to pesticide mixer/loaders and applicators in California.

Pesticide exposure occurs both when preparing (mixing/loading) the pesticide for application and when actually applying the pesticide. Equipment cleanup and repair may also contribute to exposure. These separate tasks may be done by different people or a single individual may combine them. Different formulations, handling methods, and application methods may affect levels of exposure. Good workplace hygiene dictates that the first priority in workplace safety is to put in place engineering and administrative controls to make the workplace safer rather than rely on the use of PPE to prevent exposure. Providing a physical barrier, such as closed systems for the mixer/loader and an enclosed cab or cockpit for applicators, is associated with reduced exposures of workers. The Worker Health and Safety Branch in the DPR of Cal/EPA has been monitoring various work task exposures. The results of these studies are summarized in Figures 1-4, where exposure is shown based on both time worked and amount of material handled. The studies were done using dosimeters, skin washes/wipes, and air pumps. Water-soluble packets, which are very popular with users, surpassed closed systems in reducing exposure to mixer/loaders in these studies. Hand spraying proved to present the greatest risk of exposure of the methods of application studied. It was found that the dermal route of exposure is most important, comprising 87-95% of a handler's exposure. Although this survey cannot be considered conclusive, since it leaves many formulations, systems, and methods incompletely studied or unstudied, it is clear that exposure is affected by different handling strategies. Manufacturers, regulators and users should work more closely to refine or develop new systems for safely handling pesticides.


Global estimates of acute pesticide morbidity and mortality.

Mathematical models have projected increasing numbers of pesticide poisoning throughout the world, rising from 500,000 cases/yr in 1972 to 25,000,000 cases/yr in a 1990 estimate. Among 148 outbreaks (excluding Bhopal and three probable epidemics of pesticide-related suicide) reported between 1951-90, the known number of cases was 24,731 with 1065 deaths (4.3% case fatality); these are probably underestimates. Among the known outbreaks, the most commonly identified agents were organophosphates (58), carbamates (23), chlorinated hydrocarbons (23), and organic mercurials (11). Food was the most common vehicle of exposure in these epidemics (83 outbreaks), followed by skin contact (26), multiple types of exposure (22), and respiratory exposure (16). Two countries, the United States and Thailand, accounted for more than half the reports. Both the mathematical models and the outbreak investigations support the need for continuing investigation and improved surveillance throughout the world.


Acute pesticide morbidity and mortality: California.

The California Pesticide Illness Surveillance Program collects, investigates, abstracts, and records reports received from physicians. A minority of the reports are received through the county health officers who are notified by physicians under a state requirement for reporting pesticide-caused conditions. Most of the cases are identified by review of workers' compensation records. All the cases identified are investigated by the agricultural commissioners of the counties where exposure occurred. The investigation reports are reviewed and abstracted by staff of the Worker Health and Safety Branch of the California Department of Pesticide Regulation, California Environmental Protection Agency (Cal/EPA). The crucial determination is assessment of the degree of relationship between the exposure and subsequent disease: definite, probable, possible, unlikely, or unrelated. In most years, the number of cases investigated has been between 2,500 and 3,000. Excluding antimicrobials, the number of cases found after investigation to have a definite, probable, or possible relationship with pesticide exposure has ranged from 970 (in 1989) to 1,372 (in 1988). Cases involving antimicrobials rarely were reported prior to 1987. In that year, surveillance staff began reviewing workers' compensation records personally, with the specific goal of identifying antimicrobial cases. Since then, antimicrobials have been found to account for 746-813 cases annually, primarily involving splashes and squirts to the eye and inhalation of fumes or vapors. Numbers of case reports from agricultural situations have varied irregularly, driven by small numbers of episodes concerning multiple individuals. Variability in numbers of cases involving the skin has depended almost entirely on variation in numbers of field worker dermatitis. The most common situation for field worker dermatitis has been summer work in table grapes grown in the southern San Joaquin valley. In the two years since reentry intervals for the acaricide propargite were lengthened, there have been no more major clusters of field worker dermatitis. Although the cases collected by the surveillance program are predominantly occupational, because of dependence on workers' compensation for case identification, most recorded deaths are nonoccupational. Nonoccupational fatalities include suicides, mistaken ingestion of pesticides (especially if stored in food containers), and entry into structures being fumigated. Occupational deaths are less common and more varied. The circumstances of each reported occupational death are summarized above.


Challenges in assessing long-term health effects studies.

After almost 50 yr since modern synthetic pesticides first received wide-spread use in the USA, many of the challenges that need to be met in determining their-long term effects on human health remain unanswered. Answers to many of the key challenges, such as accurate exposure assessment, pesticides' role in multifactorial causation of disease, latency, publishing of negative results, misclassification, low-level dose measurement, accurate diagnosis, the role of biomarkers, adequate study design, and adequate funding, will continue to be key factors in investigating the role, if any, of these chemicals in the transmission of human diseases.


Comparison of exposure assessment guidelines for pesticides.

The field of exposure assessment of pesticides has become well established in the past decade. Consequently, government agencies and industry groups have identified the need for guidelines for conducting studies that assess mixer/loader/applicator exposure to pesticides, as well as the exposure of individuals to residues. This paper reviews guidelines on mixer/loader/applicator exposure studies issued by the International Group of National Associations of Manufacturers of Agrochemical Products, the National Agricultural Chemicals Association, the U.S. EPA, and the World Health Organization. Mention is also made of Canadian exposure guidelines in preparation. Also reviewed are two guidelines for conducting indoor occupant exposure studies, one by the National Agricultural Chemicals Association and one by Health and Welfare Canada. The only available guideline (EPA) on assessing pesticide exposure to workers upon reentry into treated fields is also reviewed. These guidelines are reviewed and compared as to criteria for requirements of exposure studies, methodologies recommended for dermal, inhalation, and biological monitoring, quality assurance and quality control, the use of surrogate data, data reporting, and exposure calculations. From this comparison, it is evident that there has been little significant progress in the area of methodologies used for dermal exposure monitoring. The use of patches as suggested by Durham and Wolfe (1962) is still accepted and widely used, despite its limitations. However, relatively recent research in this area has shown that the fluorescent tracer technique (Fenske et al. 1986a,b) and use of full-body dosimeters may help in overcoming some of these limitations. The tracer technique is mentioned in the EPA guidelines and full-body dosimeters are addressed by EPA, WHO, and NACA. Biological monitoring can also overcome many of the limitations of passive dosimetry, but all guidelines stress the need for extensive knowledge of the pharmacokinetics and metabolism of the pesticide before this approach can be used. Rapid advancement has been made in quality assurance/quality control and analytical techniques. This has increased the level of confidence placed in exposure estimates and is evidenced by the detailed requirements of quality assurance and quality control in most of the guidelines reviewed. Guidelines on conducting indoor occupant exposure studies deal extensively with methodologies for collecting residue samples, but do not make concrete recommendations for estimating human exposure based on these residues. More research is required before the subject can be adequately dealt with in guidelines. It is encouraging that this research is being coordinated among industry, academia, and government. Further research is also needed in determining exposure to pesticides during reentry into treated areas in order to develop further guidelines.(ABSTRACT TRUNCATED AT 400 WORDS)


Saliva as a monitoring medium for chemicals.

Saliva has been used to estimate plasma levels in humans for a variety of analytes. The potential for estimating the internal dose of pesticides in humans has been demonstrated with the rat. The utility and problems of saliva-sampling techniques remain to be investigated. Measurement of pesticides and other environmental toxicants in saliva has great potential because of sampling simplicity and the potential accuracy of using the saliva concentration of a chemical to estimate its concentration in human tissues.


[Guidance of tooth eruption in the support areas using proximal grinding].

This article brings a description of a procedure for interproximal slicing. When persistence of the second deciduous molar occurs, the premolar is likely to be blocked in his eruption, while the canine is guided out of the dental arch; in these conditions it might be necessary to perform a slicing mesially of the second deciduous molar. Beforehand one should check for the posterior tooth-size and eruption pattern or sequence of each quadrant.


[Approach to pulpal and pulpo-periodontal lesions of the temporary teeth using therapeutic endodontics].

The anatomical and physiological properties of deciduous teeth make them susceptible to caries and inflammatory and infectious complications. This specificity, the proximity of the germ of the underlaying permanent tooth, and the relation of the last one to the deciduous tooth, make delicate its conservation by endodontal therapeutics after a pulpal or pulpo-periodontal affection. The success of this attempt is related to a good case-selection, based on the general condition of the child, his and his parents motivation, the condition of cariogenicity of the mouth, the analysis of the unity deciduous tooth/germ of the underlaying permanent tooth, the follow-up of the case. A success spares young children extraction of the deciduous teeth before the physiological period of permutation.


[Observations on prosthetic restoration in children].

In young children there are two frequent factors, that cause edentation: the syndrome of the sugar "baby's bottle" or the "honey dummy" and tooth-loss by trauma. Multiple extractions can be programmed in children for reason of general condition, in the major concern to remove present or potential infectious foci. Still less frequently, sometimes lately diagnosed anomalies in number or structure oblige to replacement of missing or deficient tooth. The complexity of these restorations can be related to technical problems, less frequent, in contradiction to the current opinion, to psychological problems. They have to be integrated in structures in growth, the key character of each treatment in children or adolescents. Consequently it is necessary to take account of all this factors, before to attempt this charge, and to foresee adaptations, regular control, succession of the case and interception.


[Glass ionomer cements in children].

Glass-ionomer cements are becoming more and more popular in restorative dentistry. This paper describes their principal characteristics and their use in children's dentistry; a pictorial essay illustrates some possible clinical applications.


[Multi-caries in the young child].

This article describes the clinical and therapeutic aspects of multi-caries in young children. These rampant cervical caries usually begin with the eruption of the first teeth. Two typical cases are presented in which the prolonged use of nursing bottle at bedtime and the use of pacifiers dipped into honey are responsible for the development of multi-caries. Although such patient can be treated successfully, efforts should be made to promote preventive measures and parents education.