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Purpose To evaluate the clinical outcomes and late effects of radiation therapy (RT) in localized primary orbital mucosa-associated lymphoma tissue (MALT) lymphoma (POML). Methods and Materials From 1989 to 2007, 89 patients with Stage IE POML received RT. The median age was 56 years old. Sites involved conjunctiva (59 patients [66%]), lacrimal gland (20 patients [23%]), and soft tissue (10 patients [11%]). Megavoltage beam(s) was used in 91%, electrons in 7%, and orthovoltage in 2% of cases. The dose given was 25 Gy in 97% and 30 Gy in 3% of patients. Lens shielding was possible in 57% of patients. Results The median follow-up was 5.9 years. Complete response or unconfirmed complete response was seen in 88 patients (99%). Relapse occurred in 22 patients (25%). First relapse sites were local (2 patients [9%]), in the contralateral orbit (5 patients [23%]), and distant (15 patients [68%]). The 7-year overall survival (OS), cause-specific survival (CSS), relapse-free survival (RFS), and local control (LC) rates were 91%, 96%, 64%, and 97%, respectively. Radiation-related late sequelae were documented in 40 patients (45%). Cataracts were observed in 22 patients (Grade 1 in 2 patients; Grade 3 in 20 patients). The incidence of Grade 3 cataract at 7 years was 25%. Other late sequelae (n = 28) were dry eye(s) (22 patients [Grade 1 in 14 patients; Grade 2 in 2 patients; Grade 3 in 2 patients; n/s in 4 patients), keratitis (3 patients), macular degeneration/cystoid edema (2 patients), and vitreous detachment (1 patient). Five patients developed Grade 3 noncataract late effects. Lens shielding reduced the incidence of Grade 3 cataract and all Grade ≥2 late sequelae. Seventeen patients (16 with cataracts) underwent surgery; 23 patients were treated conservatively. The outcome for managing late effects was generally successful, with 30 patients completely improved, and 9 patients with persisting late sequelae (10%). Conclusions POML responds favorably to moderate doses of RT but results in significant late morbidity. The majority of late effects were successfully managed. Lens shielding reduced the risk of cataracts and other late sequelae.

The amphiphilic gadolinium complex MS-325 ((trisodium-{(2-(R)-[(4,4-diphenylcyclohexyl) phosphonooxymethyl] diethylenetriaminepentaacetato) (aquo)gadolinium(III)}) is a contrast agent for magnetic resonance angiography (MRA). MS-325 consists of two slowly interconverting diastereoisomers, A and B (65:35 ratio), which can be isolated at pH8.5 (TyeklAr, Z.; Dunham, S. U.; Midelfort, K.; Scott, D. M.; Sajiki, H.; Ong, K.; Lauffer, R. B.; Caravan, P.; McMurry, T. J. Inorg. Chem. 2007, 46, 6621-6631). MS-325 binds to human serum albumin (HSA) in plasma resulting in an extended plasma half-life, retention of the agent within the blood compartment, and an increased relaxation rate of water protons in plasma. Under physiological conditions (37 degrees C, pH 7.4, phosphate buffered saline (PBS), 4.5% HSA, 0.05 mM complex), there is no statistical difference in HSA affinity or relaxivity between the two isomers (A 88.6 +/- 0.6% bound, r1 = 42.0 +/- 1.0 mM(-1) s(-1) at 20 MHz; B 90.2 +/- 0.6% bound, r1 = 38.3 +/- 1.0 mM(-1) s(-1) at 20 MHz; errors represent 1 standard deviation). At lower temperatures, isomer A has a higher relaxivity than isomer B. The water exchange rates in the absence of HSA at 298 K, kA298 = 5.9 +/- 2.8 x 10(6) s(-1), kB298 = 3.2 +/- 1.8 x 10(6) s(-1), and heats of activation, DeltaHA = 56 +/- 8 kJ/mol, DeltaHB = 59 +/- 11 kJ/mol, were determined by variable-temperature 17O NMR at 7.05 T. Proton nuclear magnetic relaxation dispersion (NMRD) profiles were recorded over the frequency range of 0.01-50 MHz at 5, 15, 25, and 35 degrees C in a 4.5% HSA in PBS solution for each isomer (0.1 mM). Differences in the relaxivity in HSA between the two isomers could be attributed to the differing water exchange rates.

MS-325 is a novel blood pool contrast agent for magnetic resonance imaging currently undergoing clinical trials to assess blockage in arteries. MS-325 functions by binding to human serum albumin (HSA) in plasma. Binding to HSA serves to prolong plasma half-life, retain the agent in the blood pool, and increase the relaxation rate of water protons in plasma. Ultrafiltration studies with a 5 kDa molecular weight cutoff filter show that MS-325 binds to HSA with stepwise stoichiometric affinity constants (mM(-1)) of K(a1) = 11.0 +/- 2.7, K(a2) = 0.84 +/- 0.16, K(a3) = 0.26 +/- 0.14, and K(a4) = 0.43 +/- 0.24. Under the conditions 0.1 mM MS-325, 4.5% HSA, pH 7.4 (phosphate-buffered saline), and 37 degrees C, 88 +/- 2% of MS-325 is bound to albumin. Fluorescent probe displacement studies show that MS-325 can displace dansyl sarcosine and dansyl-L-asparagine from HSA with inhibition constants (K(i)) of 85 +/- 3 microM and 1500 +/- 850 microM, respectively; however, MS-325 is unable to displace warfarin. These results suggest that MS-325 binds primarily to site II on HSA. The relaxivity of MS-325 when bound to HSA is shown to be site dependent. The Eu(III) analogue of MS-325 is shown to contain one inner-sphere water molecule in the presence and in the absence of HSA. The synthesis of an MS-325 analogue, 5, containing no inner-sphere water molecules is described. Compound 5 is used to estimate the contribution to relaxivity from the outer-sphere water molecules surrounding MS-325. The high relaxivity of MS-325 bound to HSA is primarily because of a 60-100-fold increase in the rotational correlation time of the molecule upon binding (tau(R) = 10.1 +/- 2.6 ns bound vs 115 ps free). Analysis of the nuclear magnetic relaxation dispersion (T(1) and T(2)) profiles also suggests a decrease in the electronic relaxation rate (1/T(1e) at 20 MHz = 2.0 x 10(8) s(-1) bound vs 1.1 x 10(9) s(-1) free) and an increase in the inner-sphere water residency time (tau(m) = 170 +/- 40 ns bound vs 69 +/- 20 ns free).

This article is a practical review of the current psychopharmacological agents used in the treatment of child and adolescent psychiatric disorders. Psychostimulants such as methylphenidate, dexamphetamine and pemoline are effective in the control of symptoms associated with attention deficit hyperactivity disorder. The controlled release preparations and the adjunctive use of clonidine are helpful to extend stimulant effects and control adverse effects. Tricyclic antidepressants are helpful in individual cases of child and adolescent depression, but adverse effects may limit their use. Clomipramine has been found to be effective for childhood obsessive-compulsive disorder. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) appear to be safer for depression and are also useful in obsessive-compulsive disorder. Buspirone is effective for the treatment of anxiety disorders in children. Newer atypical antipsychotics such as risperidone may have less limiting adverse effects than older antipsychotics in the treatment of psychosis and severe behaviour disorders, but the physician must be vigilant for the emergence of tardive dyskinesia. Drug treatment in children and adolescents must take into account the child's environmental influences and be part of an overall treatment plan where individual, familial and cultural issues are addressed.

(20S)-22-thiacholesterol (1) is found to be a potent competitive inhibitor of pregnenolone biosynthesis from cholesterol by purified reconstituted bovine adrenal cytochrome P-450scc. The apparent dissociation constant Kd, determined from difference spectra, is 0.6 microM, close to the value from kinetic studies for the apparent inhibition constant, Ki, of 0.8 microM. Studies of the time course of pregnenolone production indicate that under turnover conditions the competitive inhibitor (1) is converted to a tighter binding inhibitor, shown to be (20S,22R)-22-thiacholesterol S-oxide (4), with high diastereoselectivity and in a time-dependent manner. Both the diastereomeric sulfoxides, (20S,22S)-22-thiacholesterol S-oxide (3) and (20S,22R)-22-thiacholesterol S-oxide (4), exhibit properties consistent with their being competitive versus cholesterol, but the (22R)-sulfoxide (4) binds approximately 10 times more tightly than the (22S) diastereomer (3). The apparent Kd values of sulfoxides 4 and 3 are 0.1 and 1.14 microM, respectively. EPR and absorption spectroscopic studies of enzyme-inhibitor complexes suggest direct coordination of the oxygen atom of the (22R)-sulfoxide (4) with the catalytic heme center. This implies that the inhibitor operates by directly blocking further reaction at the active site heme group, with a substantial lifetime of the enzyme-inhibitor complex.

A retrospective study of 69 cases of infective endocarditis in 68 children (group I: 1971-1981; 34 children; group II: 1982-1992; 34 children) disclosed the following features: a moderate increase in the global incidence of infective endocarditis (0.5% of children hospitalized in paediatric cardiology units) and of its incidence in the very young (proportion of children less than 1 year of age: 9% in group I and 17% in group II); no rheumatic heart disease amongst predisposing heart diseases in children living in France; a major causal role of congenital heart diseases (72%), with an increasing incidence of previous operation (group I:42%; group II:56%); an increase in associated complex congenital heart diseases (group I: 11%; group II: 20%); no change in related mitral valve prolapse (5% in both groups); positive blood cultures in 76% of cases, with similar rates of Staphylococci (group I: 27%; group II: 30%) and of unusual microorganisms (15% in both groups); a major diagnostic role for echocardiography (vegetations in group II: 64%). Complications occurred in 75% of cases in both groups (pulmonary or systemic emboli, mycotic aneurysms, valvar regurgitation), leading to heart failure in 29% of group I patients and in 32% of group II patients. Mortality has decreased, from 12% in group I to 3% in group II, as a result of more frequent cardiovascular surgery (group I: 11 cases; group II: 15 cases), problems due to restrictive prostheses, and severe consequences: only 27% of group II children were cured without deterioration of their cardiac condition. These data confirm that the natural history of infective endocarditis has changed over the last two decades

An electrophysiologic study was performed in the first month of life in a patient with the congenital long QT syndrome and spontaneous episodes of 2/1 atrioventricular block. The block could be reproduced by incremental atrial pacing, and its infrahisian location was associated with a prolongation of the refractoriness in the ventricular muscle itself. Surprisingly, intravenous propranolol aggravated this phenomenon by further prolonging the QT interval. Sudden death occurred shortly thereafter during Holter monitoring and was due to a sudden resumption of normal AV conduction after an episode of 2:1 block, immediately followed by ventricular fibrillation.

EP-647 is a serum albumin-targeted magnetic resonance imaging contrast agent comprising a GdDTPA (DTPA, diethylenetriaminepentaacetate) chelate for magnetic resonance signal generation linked via a phosphodiester to a substituted biphenyl for albumin targeting. Albumin binding and relaxivity are higher than the benchmark magnetic resonance angiographic agent MS-325. EP-647 binds primarily to a unique site on serum albumin that is different from the MS-325 site and the binding sites of other drugs.

The aim of the present study was to assess the validity of different self-reported questions for measuring exercise behavior of 551 employees. Values of maximum oxygen intake, body mass index, muscular endurance, and a fitness profile, based on the individual results obtained from each of the three physiologic parameters, were used as validity criteria for the self-reported measures. The influence of fitness profile on the measures of exercise habits indicated that the fit employees reported a more active pattern of exercise behavior, participated in more strenuous physical activity, and expended a greater amount of energy in a typical week than the unfit employees. There was no gain obtained in explaining fitness categorization with a more elaborate method compared with a simple question in measuring exercise behavior. The results of the present study show that the suggested simple method (one question) for assessing exercise behavior of employees is valid and can be useful for nurses and company physicians when evaluating the baseline behavior of a group of employees to assess the impact of exercise promotion programs at the work site.

Malignant tumors in the head and neck region are rare in patients under the age of 30 years. The survival rate in our group compared favorably with the rate for adults with similar tumors and supports the administration of aggressive treatment. Radiation therapy in the formative years can arrest skeletal growth and cause tissue atrophy which produces facial asymmetry, but it does give in balance a better functional result and less mutilation than does radical surgery. The risk of development of a second malignant tumor with the administration of modern treatment appears to be minimal. There is an urgent need for better documentation of etiologic factors.

In a series of 42 bladder cancers treated with combined transurethral resection and external supervoltage Co/sup 60/ irradiation, 37% survived 3 yr or longer irrespective of stage and grade. The total calculated tumor dose of the bladder varied from just under 6000 r in 10 patients to 6000 r in 30 patients, and to over 6000 r in 2 additional patients. The overall time of treatment was 6 weeks. The delivery of a cancerocidal dose to the bladder was accompanied by increased urinary and bowel symptoms. Of 42 patients, 32 had pre-existing hematuria, and in 25 of the 32 this was the sole symptom. Thirteen other patients had multiple symptoms of urgency, frequency, dysuria, and nocturia. In 7 patients there was no aggravation of preexisting symptoms; in 31, symptoms were increased. In 16 of the 31 patients with aggravated symptoms, diarrhea was associated and in 9 of the 16 patients, diarrhea preceded urinary symptoms by a 1000 to 3000-r tumor dose. The tumor dose at which urinary symptoms first appeared was as follows: 5 cases, under 2000 r; 11 cases, 2000 to 4000 r; 12 cases, 4000 to 6000 r. Following the completion of irradiation 23 patients had persistent symptoms;more » in 10, urinary symptoms were associated with cystoscopically verified radiation cystitis which continued 6 to 12 months beyond the course of cobalt therapy. (H.H.D.)« less

The method of administration of radioactive isotopes in the treatment of pleural effusions and ascites associated with cancer will vary according to the therapeutic technic (1–5). A procedure with a suitable apparatus that utilizes an economical and sterile disposable package is described in this paper. The apparatus, shown in Figure 1, consists of: polyethylene or nylon tubing with an interior diameter of 0.70 inch; 4 stainless steel clamps; 3 No. 15 hypodermic needles of 3 1/2 inches length; 1 ampule of 5.0 c.c. Evans blue; 500 c.c. isotonic saline solution; 1 Cly-Q-Pak2; 2 Donopak 242; one Y connector.2 All the equipment is supplied sterile or can be sterilized. The radioactive isotope, whether colloidal chromic phosphate (P32) or colloidal gold (Au198), can be obtained in the exact amount prescribed. The entire apparatus is assembled within a few minutes under sterile conditions (Fig. 2). Before the hypodermic needles are inserted into the radioactive isotope vial, the air is removed from the tubing b...

Male albino rats maintained at 80% free-feed body weight were trained daily for two weeks on DRL 6-sec schedules and either suddenly shifted to DRL 12-sec schedules or maintained on DRL 6-sec. Within 30 min, 1 day, 3 days or 7 days after the step-like schedule change, the rats were killed along with ad lib food controls. Wet tissue weights for adrenals, spleens, testicles and pituitaries were taken and 20 different blood serum constitutents were measured automatically on a SMAC unit. Although the rats that had been shifted from the DRL 6-sec to DRL 12-sec condition demonstrated the usual marked elevations in response/reinforcement ratios, only alkaline phosphatase, SGOT and relative blood lymphocyte numbers differed significantly from the DRL 6-sec controls; tissue weight differences were not apparent. Highly significant differences existed between the 80% body weight, DRL tested rats and the non-tested, ad lib controls for: glucose, blood urea nitrogen, chloride, carbon dioxide, calcium, alkaline phosphatase, SGPT, triglycerides, relative testicle weights, absolute spleen weights, and body weight.

Association between bacterial endocarditis (BE) and vertebral osteomyelitis (VO) has infrequently been noted. In a retrospective analysis of BE (280 cases) and VO (150 cases) 14 cases were found to have this association. There were 12 males and 2 females, ages ranging from 39 to 72 years, mean age 56.6. Blood cultures were positive for Streptococcus viridans (6 cases). Str. faecalis (4 cases), staphylococcus (2 cases), Gram negative bacteria (1 case). Organism was not isolated in one case. Fever and severe back pain antedate the diagnosis of VO 3.5 and 2.5 months. X rays films of the spine and bone scans (4 cases) revealed lumbar (6 cases) or cervical (4 cases), or dorsal (3 cases) or combined cervical and dorsal (1 case) locations. History of murmur (4 cases) and development of mitral (8 cases) or aortic (4 cases) or combined mitral and aortic (2 cases) insufficiencies were consistent with concomitant BE. Echocardiogram revealed vegetations in 6 out of 9 cases. Patients received antibiotic therapy for 3.5 months. Ten patients were cured with antibiotics only, 4 required valve replacement. One died. Thus age, sex, history of heart disease, valvular involvement, duration of symptoms prior to admission and bacteriological pictures are the same in BE with VO as in BE without VO. Survival rates are also the same if early recognition of BE and VO with prompt and prolonged antibiotic therapy may prevent severe haemodynamic or vertebral problems.