Eosinophilic fasciitis associated with hypereosinophilia, abnormal bone-marrow karyotype and inversion of chromosome 5.

We report the case of a male patient presenting with eosinophilia, pulmonary oedema and eosinophilic fasciitis (EF). He had the classic clinical appearance and magnetic resonance imaging of EF. Cytogenetic analysis of the bone marrow revealed a previously undescribed pericentric inversion of chromosome 5. Overall, the presentation was consistent with a diagnosis of chronic eosinophilic leukaemia, not otherwise specified (CEL-NOS). Dermatologists should consult a haematologist in cases of EF, in order to rule out possible haematological malignancies.

Three-dimensional mesoporous structures fabricated by independent stacking of self-assembled films on suspended membranes.

We report an original iterative method for fabricating three-dimensional mesoporous structures by independently stacking multiple self-assembled block copolymer films supported by Si membranes. A first layer is formed on the substrate by a self-assembled PS-b-PMMA (polystyrene-block-poly(methyl methacrylate)) film. A porous, permeable Si membrane deposited on top of the first block copolymer film provides mechanical support, preventing pattern collapse during the wet developing used to selectively remove the PMMA component of the PS-b-PMMA film. A second, dense Si membrane is deposited to seal the porous membrane, resulting in an impermeable coating suspended atop the self-assembled mesoporous polystyrene structures. The process can then be iterated using the sealed membrane as the new substrate to support a subsequent self-assembled block copolymer film. This multilayer approach provides a flexible three-dimensional fabrication technique where, in each layer, pattern morphology, domain orientation and degree of ordering can be designed independently. Furthermore, the process is compatible with electron-beam directed assembly, used to achieve regular patterns with feature density multiplication at any level in the stack.

Measurement of monoclonal antibody concentrations in hybridoma cultures: comparison of competitive inhibition and antigen capture enzyme immunoassays.

Competitive inhibition and antigen capture enzyme immunoassays were compared for the measurement of mouse monoclonal IgGl antibody produced by a hybridoma culture. Both methods yielded standard curves that were linear over several orders of magnitude, and both were comparable in sensitivity (10 ng/ml). However, the slope of the antigen capture curve was flatter than the slope for competitive inhibition. This difference in slope, coupled with a larger average standard deviation for each point on the standard curve for antigen capture, resulted in a significantly larger range of variability in IgGl levels. It is concluded that the competitive inhibition enzyme immunoassay method is better suited to the precise quantification of mouse monoclonal antibodies in hybridoma culture supernatants.

Intravenous immunoglobulin in neonatal group B streptococcal disease. Pharmacokinetic and safety studies in monkeys and humans.

Numerous studies have suggested that opsonic antibody is important in neonatal immunity to group B streptococci. Immunoglobulin G is primarily transferred from the mother to the fetus across the placenta in the last few weeks of pregnancy. Premature babies may, therefore, not acquire sufficient opsonic antibody to protect them from infection with group B streptococci. Although maternal immunization may provide adequate maternal opsonic antibody, premature infants with antibody deficiency may remain susceptible to infection. Intravenous immunoglobulin administered to term pregnant rhesus monkeys did not provide reliable levels of serum opsonic activity to group B streptococci in their offspring. Pharmacokinetic and safety studies were also performed in human neonates. Significant elevations in group B streptococcal-specific IgG did occur in human neonates given 500 mg/kg intravenous immunoglobulin and the infusions appeared safe and well tolerated. The availability of intravenous immunoglobulin with functional activity against group B streptococci may provide a rapid and effective method of delivering opsonic antibody to neonates.

Pelvic control following external beam radiation for surgical stage I endometrial adenocarcinoma.

PURPOSE: To determine if postoperative external pelvic radiation (EBRT), without vaginal brachytherapy, is sufficient to prevent vaginal cuff and pelvic recurrences in patients with surgical Stage I endometrial adenocarcinoma (ACA). METHODS AND MATERIALS: The records of 122 patients with surgical Stage I endometrial cancer were reviewed. There were 87 patients with ACA who received EBRT alone and are the subject of this study. Their radiation records were reviewed. All patients underwent exploration, total abdominal hysterectomy, and bilateral salpingo-oophorectomy (TAH BSO), and pelvic and paraaortic lymph node sampling. They were staged according to the FIGO 1988 surgical staging system recommendations. Postoperatively, pelvic EBRT was administered by megavoltage equipment using four fields, to a total dose of 45 to 50.4 Gy. Actuarial survival and disease free survival were calculated according to Kaplan-Meier Method. RESULTS: Twenty-seven patients with Stage IA Grade 1 or 2 ACA with less than one-third myometrial invasion, who did not receive EBRT, and eight patients with histology other than adenocarcinoma (i.e., serous papillary, mucinous, etc.) were not included in the study. For the remaining 87 patients who are in the study group, the median follow-up was 52 months (range: 12-82 months). The 5-year overall survival for these 87 patients was 92%, with a disease-free survival of 83%. There were no tumor recurrences in the upper vagina or in the pelvis. Two patients developed small bowel obstruction (no surgery required), and one patient developed chronic enteritis. CONCLUSION: Adjuvant external pelvic radiation, without vaginal brachytherapy, prevents pelvic and vaginal cuff recurrences in surgical Stage I endometrial ACA.

Palladium-103 versus iodine-125 for ophthalmic plaque radiotherapy.

PURPOSE: A dosimetry study comparing the use of I-125 vs. Pd-103 radioactive seeds for ophthalmic plaque brachytherapy. METHODS AND MATERIALS: Palladium-103 (Pd-103) seeds in ophthalmic plaques were used to treat 15 patients with intraocular malignant melanoma. Computer-aided simulations were performed to evaluate the intraocular dose distribution of I-125 versus Pd-103 ophthalmic plaques (delivering equivalent apex doses). Seven target points were selected. Starting at the outer scleral surface, four were located along the central axis of the plaque: the 1 mm point (the inner sclera), the 6 mm point, the tumors apex, and the opposite eye wall. We also evaluated the fovea, optic nerve, and the lens because they were considered to be critical structures. RESULTS: These studies demonstrated that the lower energy photons generated by Pd-103 seeds (average 21 KeV) in ophthalmic plaques were more rapidly absorbed in tissue than photons generated by I-125 (average 28 KeV). Therefore, during ophthalmic plaque radiotherapy, Pd-103 photons were found to be more rapidly absorbed within the tumor and less likely to reach most normal ocular structures. On average, the use of Pd-103 decreased the dose to the fovea by 5.7%, to the optic nerve by 8.4%, to the lens by 26%, and to the opposite eye wall by 38.4%. CONCLUSION: Palladium-103 ophthalmic plaque brachytherapy resulted in slightly more irradiation of the tumor and less radiation to most normal ocular structures.

Radiotherapy for age-related macular degeneration: preliminary results of a potentially new treatment.

PURPOSE: Neovascular macular degeneration is the leading cause of severe blindness in North America today. Limited treatments are available for this disease process. A Phase I/II study was performed to determine the toxicity and efficacy of external beam radiotherapy in patients with age-related subfoveal neovascularization. METHODS AND MATERIALS: Between March 1994 and June 1995, 52 patients with a mean age of 80 (60-92) were enrolled. These patients were either not eligible or were poor candidates for laser photocoagulation, primarily because of the subfoveal location of the neovascularization. Initial visual acuities ranged from 20 out of 32 to finger counting at 3 feet. All patients underwent fluorescein angiographic evaluation and documentation of their neovascular disease prior to irradiation. Patients were treated with a single lateral 4- or 6-MV photon beam, to a dose of 14-15 Gy in eight fractions over 10 days. The field size averaged 5 x 3 cm. RESULTS: No significant acute morbidity was noted. All patients underwent ophthalmic examinations and repeat angiography at 1 and 3 months posttreatment and then at 3-month intervals. With a mean follow-up of 7 months (3-18 months), 41 patients (79%) are within two lines of their pretreatment visual acuity. On angiographic imaging, there was stabilization of subfoveal neovascular membranes in 34 patients (65%). New neovascular membranes have been noted in five patients. CONCLUSIONS: It appears that radiotherapy can affect active subretinal neovascularization, but it is unlikely to prevent new neovascular events produced by this chronic disease. Further investigation is warranted.

Delayed hypersensitivity and local control of patients treated by radiotherapy for head and neck cancer.

Delayed hypersensitivity of sixty-three patients with head and neck cancer treated by radiotherapy was correlated with short-term tumor control. Of eighteen patients with early disease, sixteen were DNCB-reactive and all were controlled and one of the two nonreactors was controlled. Thirty-three of forty-five patients with advanced tumors were reactive and nineteen were controlled. Only two of the twelve nonreactors were controlled.

The conservative management of anorectal cancer by radiotherapy.

Thirteen patients with an anal or rectal carcinoma were given curative radiotherapy. Four had medically inoperable tumors, one had a surgically inoperable tumor and eight refused abdominoperineal resection. Six patients received external radiotherapy only. Seven patients received external radiotherapy and an interstitial implant. Nine of thirteen patients (60 per cent) are alive without evidence of disease from fifteen to fifty-five months (average, 30 months). Six of seven patients who received external radiotherapy combined with an interstitial implant were controlled locally, whereas three of six patients who received external radiotherapy only were controlled. Patients who underwent total excision and/or fulguration prior to irradiation had better local control than those who underwent either biopsy only or a subtotal excision. This treatment method may be offered as an alternative to abdominoperineal resection in patients who are medically unfit or who refuse surgery.

Physicians prefer goal-oriented note format more than three to one over other outcome-focused documentation.

To assess preference for outcome-focused nutrition notes, two note formats were selected from the literature and tested against a modified, goal-oriented format. Focus charting and intervention, evaluation, and revision (IER) formats were compared with a charting-by-exception style that was modified to include goals and reassessment of risk. Notes were handwritten in each format and contained the same information. Physicians were asked to choose their preference and explain why that format was selected. Initially, focus charting was tested against the goal-oriented format. The more popular of the two was then tested against the IER format. Nineteen physicians were surveyed by a registered dietitian for each comparison. Physicians preferred the goal-oriented format over focus charting and IER formats 9:1 and 3:1, respectively. In the first survey, physicians preferred the goal-oriented format because the plan was clearly stated, thereby rendering the note easier to understand. The goal-oriented format was preferred in the second survey because the note was considered to be concise and easy to read and contained expected outcomes. Physicians want short communication that includes easily identifiable goals and plans. We recommend that experienced dietitians use the goal-oriented format developed for this study, and preferred by physicians, for follow-up nutrition notes.

Limited surgery and radiotherapy in the treatment of localized breast cancer. An overview.

Conservative surgery and modern radiotherapy has been found to be as effective as mastectomy in treating early breast cancer. There is no difference in survival or local control. Irradiation following tumorectomy has a low incidence of complications, and yields excellent cosmetic results and breast preservation.

Interleukin-2 and concanavalin A upregulate a cat2 isoform encoding a high affinity L-arginine transporter in feline lymphocytes.

The immunological responses of activated lymphocytes are associated with increased nitric oxide (NO) biosynthesis. Studies in the literature have primarily approached control of NO by focusing on the regulation of the nitric oxide synthase (NOS) isoforms. However, the present study approaches the control of NO synthesis by addressing the regulation of L-arginine availability to lymphocytes via regulation of membrane transport. The guanidino nitrogen of L-arginine is the sole biosynthetic precursor of NO. We investigated cytokine and mitogen regulation of membrane L-arginine transporters for the first time in feline cells. Feline peripheral blood mononuclear cells were treated with interleukin-2 and concanavalin A, then alternatively spliced isoforms of L-arginine transporters known in other species were probed by RT-PCR, using various oligonucleotide primers that hybridized to several regions in common with the isoforms. Both high affinity and low affinity isoforms are encoded by mRNAs arising from mutually exclusive alternative splicing of the primary transcript. A region of 123 bp was obtained that encoded an extracellular polypeptide loop of 41 amino acids. The sequence of this region represented the high affinity L-arginine substrate binding site of a CAT2 transporter polypeptide isoform, but not the CAT2a isoform low affinity binding site. Neither of the inducible isoforms were constitutively expressed in unstimulated feline cells. This is the first report demonstrating that domestic cats possess the cat2 gene encoding an inducible L-arginine transporter, and, furthermore, that the high affinity isoform transcript is activated by interleukin-2 and concanavalin A in feline lymphocytes.

Delayed hypersensitivity in patients treated by curative radiotherapy. Its relation to tumor response and short-term survival.

Delayed hypersensitivity, as determined by skin reactivity to 2-4 dinitrochlorobenzene (DNCB), was tested in 112 patients prior to their undergoing curative radiotherapy. Of the strong DNCB reactors, 84% had an excellent radiation tumor response, while only 48% of the negative reactors had an equivalent response. Almost twice as many strong DNCB reactors were alive and free of disease (NED) at 6 months (70% vs. 38% for nonreactors). Similarly, the positive DNCB reactors had a median survival of 18 months, compared to 10 months for the nonreactors.

The effect of radial radiotherapy on delayed hypersensitivity and the inflammatory response.

Delayed hypersensitivity to DNCB and the inflammatory response to croton oil wereevaluated in 144 and 121 patients respectively, prior ro and 3 to 6 months following curative radiotherapy. Eighty-one patients had in vitri lymphocyte transformation by PHA;59 (41%) were nonreactors to DNCB and 27 (22%) to croton oil; 29 of 59 (49%) initiallyreactive became anergic. Similiar improvement of the inflammatory response was obtained. Patients who became DNCB-reactive following radiotherapy had the same favorable prognosis as those who were initially reactive. Radiotherapy did not adversely affect either delayed hypersensitivity or the inflammatory response. There was a 50% decrease in PHA stimulation and lymphocyte count after treatment. No correlation was found between DNCB reactivity and lymphocyte transfermation prior to or following radiotherapy. The evaluation of the effect of radiotherapy on cell-mediated immunity depends on the tests used.

Effects of fat-supplemented diets on plasma lipoproteins and the apoprotein/lipid ratios in rabbits.

Male white New Zealand rabbits were maintained for 4 weeks on one of the following diets: (1) normal chow diet, (2) chow plus 1% cholesterol and 3% coconut oil, (3) diet 2 plus 100 IU alpha-tocopherol, and (4) diet 2 plus 100 ml 10% alcohol daily. Total serum cholesterol, HDL cholesterol, and triglycerides were significantly increased with diets 2, 3, 4. These diets resulted in a shift in distribution of the lipid transported so that a much greater percentage was transported in LDL and VLDL and a much smaller fraction in HDL. The ratio of protein to lipid decreased drastically in LDL in groups 2, 3, and 4 as compared to normals; it also decreased markedly in VLDL of groups 3 and 4. The ratio of protein to lipid decreased in the HDL of group 2, but not in 3 and 4. Neither vitamin E nor alcohol supplementation changed the hyperlipemic response to the high fat diet. These data indicate that in the hyperlipidemic rabbits, the composition of VLDL and LDL were altered, and that a change in the relative distribution of lipids among the lipoprotein classes occurred.

Prophylaxis against vitamin D deficiency in the elderly by regular sunlight exposure.

The effects of regular sunlight exposure on levels of vitamin D metabolites and on other indices of calcium metabolism have been studied in elderly rest-home residents. Fifteen subjects who formerly went outdoors very infrequently were studied over a 4-week period while spending 0, 15 or 30 minutes daily sitting on the rest-home verandah. During this time, levels of 25-hydroxyvitamin D [25(OH)D] rose by 7.4 +/- 1.2 (s.e.m.) microgram/1 in the group spending 30 minutes per day outdoors (P less than 0.005) and there was a smaller but nonsignificant increase in the 15 minutes per day group also. Serum 1,25 (OH)2D levels did not change during the study but serum ionized calcium and alkaline phosphatase showed small, but significant, decreases. Intestinal strontium absorption increased in both treatment groups (P less than 0.05), indicating a similar change in calcium absorption. It is concluded that 30 minutes spent outdoors each day leads to a substantial increase in 25(OH)D levels in elderly subjects and that this has significant effects upon other indices of calcium metabolism. This regimen provides a safe and inexpensive method for the prevention of osteomalacia in frail elderly subjects.

Palladium 103 plaque radiotherapy for uveal melanoma. Clinical experience.

PURPOSE: To evaluate the effect of palladium 103(103Pd) ophthalmic plaque brachytherapy on patients with uveal melanoma. BACKGROUND: Radioactive 103Pd seeds have become available for plaque brachytherapy, and computer-aided simulations have compared the intraocular dose distribution of 103Pd versus iodine 125 (125I) plaques in patients with uveal melanoma. The use of the lower-energy radionuclide 103Pd increased the radiation to the tumors and decreases irradiation of most normal ocular structures. METHODS: The authors have begun a phase 1 clinical trial evaluating the effect of 103Pd ophthalmic plaque radiotherapy on intraocular tumors. Uveal melanoma was diagnosed, and the patients were found to be negative for metastatic disease. All patients were given one 103Pd radioactive plaque treatment, and six patients also were given adjuvant microwave hyperthermia. RESULTS: Palladium 103 ophthalmic plaque radiotherapy was used to treat 23 patients with uveal melanoma. Patients were followed for up to 27 months (mean, 13.5 months). One eye was enucleated for progressive tumor enlargement (4 months after treatment). One patient died (of metastatic melanoma). Eight patients have lost greater than two lines of visual acuity, one has gained more than two lines. Fifteen patients (65%) were within two lines or had better than their preoperative visual acuity. Relating to the effect of treatment on visual acuity, 15 (65%) tumors were located equal to or less than 2 mm from the fovea. CONCLUSION: Palladium 103 ophthalmic plaque radiotherapy was noted to control the growth of uveal melanomas. Compared with other forms of plaque radiotherapy at this follow-up interval, the authors have noted no new complications, no difference in local control, and/or changes in tumor response to treatment. More long-term follow-up will be required to demonstrate differences between 125I and 103Pd ophthalmic plaque brachytherapy.