High-energy radiation monitoring based on radio-fluorogenic co-polymerization II: fixed fluorescent images of collimated x-ray beams using an RFCP gel.

We have produced an optically clear, close to water-equivalent gel that is radio-fluorogenic, i.e. fluoresces in UV light after exposure to high-energy radiation. Its potential as a 2D and 3D dosimetric medium is demonstrated by fixed fluorescent images of the cross-section, track and intersection of collimated (10 × 10 or 5 × 5 mm(2)) 205 kVp x-ray beams. The images, produced by doses on the order of 10 Gy, are formed instantaneously and can be digitally recorded and scanned with a spatial resolution on the order of 0.1 mm. No loss of spatial resolution occurs on standing under ambient conditions for at least 3 days.

High-energy radiation monitoring based on radio-fluorogenic co-polymerization. I: Small volume in situ probe.

A method of radiation dosimetry is described which is based on the radiation-induced initiation of polymerization of a bulk monomer (e.g. methyl methacrylate) containing a small concentration (about 100 ppm) of a compound which is non-fluorescent but which becomes highly fluorescent when it is incorporated into a growing polymer chain of the bulk monomer. We call the overall process 'radio-fluorogenic co-polymerization' or RFCP for short. The method is illustrated by results on the in situ monitoring of the accumulated dose within the irradiation chamber of a cobalt-60 gamma-ray source using a small plastic capsule containing about 0.2 ml of an RFCP solution. Remote monitoring of the fluorescence is carried out on a timescale of seconds using optical fibres connecting the probe to a 360 nm LED excitation source and a miniature spectrophotometer. The fluorescence is permanent and the intensity is linearly proportional to the accumulated dose from a few tenths of a gray up to hundreds of gray. The sensitivity to dose depends on the polymerizable monomer used and obeys a square root dependence on dose rate over the range studied, 0.27-3.76 Gy min(-1). The polymeric nature of the fluorescent product suggests that the RFCP effect could be used to provide fixed two- or three-dimensional fluorescent images of dose deposition in gel films or phantoms.

Symmetry breaking in the relaxed S(1) excited state of bianthryl derivatives in weakly polar solvents.

The flash-photolysis time-resolved microwave conductivity technique (FP-TRMC) has been used to investigate the nature of the relaxed S(1) state of 9,9'-bianthryl (AA), 10-cyano-9,9'-bianthryl (CAA), and 10,10'-dicyano-9,9'-bianthryl (CAAC). Changes in both the real, Deltaepsilon' (dielectric constant), and imaginary, Deltaepsilon' ' (dielectric loss), components of the complex permittivity have been measured. The dielectric loss transients conclusively demonstrate the dipolar nature of S(1) for all three compounds in the pseudopolar solvents benzene and 1,4-dioxane, and even in the nonpolar solvents n-hexane and cyclohexane. The required symmetry breaking is considered to result from density and structural fluctuations in the solvent environment. The dipole relaxation times for AA (CAAC) are ca. 2 ps for the alkanes and 7.9 (5.3) and 14 (14) ps for benzene and dioxane, respectively. The time scale of dipole relaxation for the symmetrical compounds is much shorter than that for rotational diffusion and is attributed to intramolecular, flip-flop dipole reversal via a neutral excitonic state. The dipole moment of the transient dipolar state is estimated to be ca. 8 D, that is much lower than the value of ca. 20 D determined from the solvatochromic shifts in the fluorescence in intermediate to highly polar solvents which corresponds to close to complete charge separation. For the asymmetric compound, CAA, a dipole moment close to 20 D is found in all solvents, including n-hexane. Dipole relaxation in this case occurs on a time scale of several hundred picoseconds and is controlled mainly by diffusional rotation of the molecules. The mechanism and kinetics of formation of the dipolar excited states are discussed in the light of these results.

Colchicine for persistent constipation after total abdominal colectomy with ileorectostomy for colonic inertia.

Severe constipation caused by colonic inertia may be associated with a generalized gastrointestinal dysmotility syndrome. Patients with severe constipation pose a significant challenge in terms of management. Failure of medical therapy usually leads to surgery in the form of a subtotal colectomy. Most patients develop diarrhea after the surgery, but a subgroup of patients continue to experience constipation. We report the case of such a patient who underwent a total abdominal colectomy and ileorectostomy for intractable constipation. He continued to have constipation after the surgery that was responsive only to a gallon of bowel-cleansing solution. A treatment trial of colchicine was partially unsuccessful when used on its own, but a combination of colchicine and a lesser dose of Colyte was found to be effective in maintaining regular bowel movements.

Malignant neoplasms subsequent to treatment of inflammatory bowel disease with 6-mercaptopurine.

OBJECTIVE: Most complications of 6-mercaptopurine (6MP) used in the treatment of inflammatory bowel disease (IBD) occur early, whereas neoplasms occur late in the course. Concern persists that the risk is increased when 6MP is used. We report our experience with malignant tumors developing over 27 yr of treating IBD patients with 6MP. METHODS: A total of 591 patients with IBD treated with 6MP between 1969 and 1997 were followed or traced until present to identify all malignant tumors and blood dyscrasias that had developed to determine the type, distribution, and duration of the IBD, the dose and duration of 6MP therapy, the concurrent versus previous use of 6MP, the incidence and probable relationship of 6MP to specific neoplasms, and whether the 6MP had been effective in treatment. RESULTS: A total of 550 patients (93%) fulfilled the criteria for follow-up; these included 380 with Crohn's disease (CD) and 170 with ulcerative colitis (UC). Twenty-five patients had developed neoplasms (16 of 380 CD and nine of 170 UC) (p = 0.66). In half of the cases, the goal of therapy had been achieved with 6MP. In 10 patients, the neoplasm was diagnosed while the patients were taking 6MP (40%) and in 15, many years after the 6MP had been terminated (60%). The incidence of neoplasms (25 of 550) was 2.7/1000 patient-years of follow-up. The most common neoplasms were found in the bowel (eight of 550, 1.6%; five CD, and three UC), and breast (three, 0.5%; two CD, and one UC). Non-Hodgkins lymphomas occurred in two patients with CD; one was cerebral and the other abdominal. One patient with CD developed leukemia. The duration of 6MP therapy ranged from 5 months to 22 yr, with a mean of 5 yr. The dose of 6MP ranged from a quarter of a tablet/day (12.5 mg) to 100 mg/day, with the majority in a range from 50 to 75 mg/day. CONCLUSION: In no instance could a neoplasm be attributed to the use of 6MP. The incidence of colon cancer is not greater than that with long standing colitis. Suspicion of a relationship between 6MP and leukemia/lymphoma persists, but the incidence is low. This must be weighed against the improved quality of life due to 6MP for patients with IBD.

Shingles during the course of treatment with 6-mercaptopurine for inflammatory bowel disease.

OBJECTIVE: Our aim was to study the frequency, severity, and outcome of patients with Crohn's disease and ulcerative colitis treated with 6-mercaptopurine (6MP) who developed shingles during treatment, and to recommend management. While varicella can be severe in young people immunocompromised by steroids, the incidence of herpes zoster in older people with inflammatory bowel disease (IBD) and whether its severity is influenced by 6MP and azathioprine are unknown. METHODS: Data were collected from our IBD Center on 550 patients with IBD to identify those who developed shingles while on 6MP, its severity, the dose and duration of 6MP, and the management of the 6MP. RESULTS: Twelve of 550 patients with IBD treated with 6MP developed shingles. In two with herpes zoster ophthalmicus the pain was prolonged, and one patient developed encephalitis which was brief and uncomplicated; in nine patients the course was benign. Acyclovir should be the treatment of choice even though it was available in only three cases. CONCLUSIONS: Shingles occurs more often in IBD patients treated with 6MP than in those who are not, but the course is usually benign and there has been no mortality. The 6MP should be stopped temporarily until severity is established but if the underlying disease warrants further treatment the 6MP should be restarted.

The osteogenic response to distant skeletal injury.

We tested the hypothesis that when one bone of the skeleton is injured, others experience an osteogenic response. Although similar or related phenomena have been observed previously, the purposes of the study were to determine if this response was reproducible, to characterize it in terms of its magnitude and duration, and to show how it is related to the type of injury sustained. To obtain this information, a model was used in which an intramedullary nail was implanted in the femur and a standard closed fracture was subsequently produced. The osteogenic response was measured by histomorphometry. Eight-four nine-week-old male Sprague-Dawley rats were divided into seven groups of twelve animals each. Groups I and II consisted of control animals in which no injury was produced. In Group-III rats, cortical drilling of the intercondylar notch and piriformis fossa of the right femur was performed, without intramedullary nailing. In Groups IV through VII, half of each group received intramedullary nails only, and in the other half intramedullary nailing was done and a closed transverse diaphyseal fracture was produced. With two different fluorochrome labels, rates of mineral apposition were measured in the left and right tibiae of all animals. The labeling periods differed in each group and were designed to determine when the peak response occurred, how long it lasted, and whether aging during the course of the experiment affected the response.(ABSTRACT TRUNCATED AT 250 WORDS)

Neutral protein-degrading enzymes in experimental fracture callus: a preliminary report.

The process of endochondral fracture healing is biochemically similar to growth plate calcification. Recent studies have identified potentially important roles for proteoglycan-degrading enzymes in the growth plate. The purpose of the study described herein was to identify, in healing fractures, neutral enzyme activities capable of degrading proteoglycans and other matrix proteins. Two sets of 60 male Sprague-Dawley rats underwent the production of closed femoral fractures. Calluses were retrieved at timed intervals, and cell and matrix vesicle fractions were prepared for electron microscopy, neutral peptidase, and alkaline phosphatase assays. In another group of 10 animals, fractions were prepared from 14-day calluses and examined for proteoglycanase activity. In the cell fractions, alkaline phosphatase, alanyl-beta-naphthylamidase, aminopeptidase, and endopeptidase activities showed somewhat parallel distributions peaking at approximately 14-17 days. In the matrix vesicle fractions, similar relative distributions were observed for alkaline phosphatase and endopeptidase. However, here the peak activities occurred up to 3 days later than they did in the cell fractions. Significant proteoglycanase activity was confirmed in both cell and matrix vesicle fractions. These findings are consistent with the hypotheses that (a) neutral peptidases, by virtue of their temporal expression in parallel with alkaline phosphatase, may be involved in preparing fracture callus matrix for calcification; and (b) matrix vesicles may convey certain of these enzymes to sites of both matrix degradation and calcification, since the same activities found in cells are found in matrix vesicles a few days later. The possibility that some of these enzymes are involved in growth factor activation remains to be investigated.

Fracture healing and osteocalcin metabolism in vitamin K deficiency.

Osteocalcin (a vitamin K-dependent, bone-specific protein) is widely accepted as a marker of osteoblastic activity. The present study was conducted to determine if a vitamin K deficiency would affect fracture healing by virtue of an alteration in osteocalcin metabolism. Thirty male Sprague-Dawley rats were divided into two groups. The control group was fed a diet that was lacking in, but offered water replete with vitamin K. The experimental group was fed a vitamin K-deficient diet and was offered water that was lacking in vitamin K. After two weeks, vitamin K deficiency was established in the experimental group as shown by decreased urinary excretion of gamma-carboxyglutamic acid and an elevation of serum prothrombin times to between two to two and one-half times the control values. At this time, a standard, closed femoral fracture was produced. Six weeks later, the animals were killed. The bones were biomechanically tested in torsion. Subsequent to mechanical testing, the calluses were retrieved, and the osteocalcin content and the degree of gamma carboxylation of the osteocalcin in the calluses were measured. The results show that despite significant alterations in the gamma carboxylation of osteocalcin and elevation of prothrombin times to two to two and one-half times the control values, there were no differences in the mechanical properties of the calluses. Furthermore, there were no differences in the content or gamma carboxylation of osteocalcin in these calluses. Apparently, in vitamin K deficiency, fracture callus achieves normal mechanical properties and may have a mechanism for the gamma carboxylation of glutamic acids in osteocalcin despite a substantial depression of this activity in the rest of the body.

Fast protonation of adenosine and of its radical anion formed by hydrated electron attack; a nanosecond optical and dc-conductivity pulse radiolysis study.

The study of the reaction of the hydrated electron with adenosine by optical and dc-conductivity pulse radiolysis on nano- and microsecond timescales has been carried out in an attempt to answer the question whether the electron adduct radical becomes protonated or not. The following conclusions have been reached: (1) the reaction of the hydrated electron with adenosine is followed by a water-mediated protonation, which must be complete with 5 ns; (2) no spectral indication of a further protonation of the protonated electron adduct of adenosine of 2'-deoxyadenosine has been found between 40 and 5000 ns; (3) the equilibrium reaction between radiation produced H3O+ and adenosine with a pKa of 3.5 plays an important role in the kinetics of the conductivity transients.

Reversible defect of neutrophil chemotaxis and random migration in primary hyperparathyroidism.

Chemotactic and random migrations of neutrophils derived from four patients with primary hyperparathyroidism were found to be defective. These abnormalities improved significantly in parallel with the decrease in serum calcium and parathormone and with the increase in serum phosphorus concentration after surgical removal of the adenoma. These observation suggest a possible role for parathormone phosphorus and calcium in the motility of neutrophils.

Clinical significance of the satellited short arm of human chromosome 17 (17ps +) : a rare heteromorphism?

A 43-year-old impotent male Caucasian had a chromosomal constitution of 46,XY,17ps+. The satellited chromosome 17 was also present in his sister. There is no suggestive evidence that this satellited chromosome causes any clinical abnormality. Based on multiple banding techniques, it is concluded that the 17ps+ is a rare chromosomal heteromorphism.

Cytogenetic polymorphism or Y/15 translocation in a black male with ambiguous genitalia.

A black male with ambiguous genitalia was found to have presumptive Y/15 translocation (46,XY,der(15) ? t(15;Y) (13;q12.2). The proband inherited this translocation from his father. All banding techniques were utilized to determine whether this was a polymorphism or a Y/15 translocation. No definite conclusion was reached but the results of QFQ, RFA, CBG, and GTG banding techniques are highly suggestive of Y/15 translocation.

Primary amenorrhea in a black female with duplication and inversion of the secondary constriction regions of chromosome 9.

A 36-yr-old black female presented with primary amenorrhea. The chromosomal constitution based on QFQ (Q bands by fluorescence using quinacrine) RFA (R bands by fluorescence using acridine orange), GTG (G band by Giemsa using trypsin), and CBG (C band by Giemsa using barium hydroxide) techniques was 46, XX, duplicated (9; q12), inverted (9; p12q12.1) in lymphocytes and skin fibroblasts. Both sex chromosomes were normal. Buccal smear revealed 22% Barr bodies. Duplication and inversion of secondary constriction regions of chromosome 9 may possibly be associated with abnormal clinical features.