Antibody-mediated marrow failure after allogeneic bone marrow transplantation

Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft failure, either by antibody-dependent cell-mediated cytotoxicity (ADCC), or complement- mediated cytotoxicity. In the case of HLA Class I disparity, where all donor cells express the target antigen, the presence of alpha-donor antibody was associated with complete graft failure and death. In the case of ABO blood group antigen disparity, the presence of alpha-donor antibody resulted in erythroid hypoplasia. The latter cases proved informative insofar as they established that host antibodies could persist for more than 18 months after chemoradiotherapy and impair marrow function.     

Methotrexate/narrowband UVB phototherapy combination vs. narrowband UVB phototherapy in the treatment of chronic plaque‐type psoriasis – a randomized single‐blinded placebo‐controlled study

Background Psoriasis is a chronic, recurring inflammatory disease affecting the skin, joints and nails that has a significant negative impact on the quality of life. Efficacy of combination of methotrexate/narrowband ultraviolet B (NBUVB) phototherapy in the treatment of psoriasis has been rarely assessed. Objectives To compare the efficacy of methotrexate/NBUVB phototherapy combination vs. NBUVB phototherapy in the treatment of chronic plaque psoriasis. Methods Forty patients with chronic plaque‐type psoriasis (body surface area involvement >10%) were randomized to receive either methotrexate/NBUVB phototherapy (group A) or placebo/NBUVB phototherapy (group B). End point of treatment was 75% reduction in Psoriasis Area and Severity Index (PASI) Score or upto 6 months, whichever was earlier. Patients were then followed up for a period of 12 weeks for assessment of relapse. Results Of 40 patients, 37 completed the treatment period and 29 both the treatment period and follow‐up. PASI 75 was achieved in 19/20 patients in group A and 14/20 patients in group B (P < 0.04). The mean number of weeks(P = 0.001), the mean cumulative dose of NBUVB (P = 0.001) and the mean number of phototherapy sessions (P = 0.0001) required to achieve PASI 75 were significantly less in group A compared with group B. There was no significant difference in the number of patients who relapsed during the follow‐up period (P = 0.68). Conclusion Combination of methotrexate and NBUVB phototherapy provides more rapid clinical improvement compared with NBUVB monotherapy in the treatment for chronic plaque‐type psoriasis.     

A comprehensive review of prostate cancer brachytherapy: defining an optimal technique.

PURPOSE: A comprehensive review of prostate cancer brachytherapy literature was performed to determine if an optimal method of implantation could be identified, and to compare and contrast techniques currently in use. METHODS AND MATERIALS: A MEDLINE search was conducted to obtain all articles in the English language on prostate cancer brachytherapy from 1985 through 1998. Articles were reviewed and grouped to determine the primary technique of implantation, the method or philosophy of source placement and/or dose specification, the technique to evaluate implant quality, overall treatment results (based upon pretreatment prostate specific antigen, (PSA), and biochemical control) and clinical, pathological or biochemical outcome based upon implant quality. RESULTS: A total of 178 articles were identified in the MEDLINE database. Of these, 53 studies discussed evaluable techniques of implantation and were used for this analysis. Of these studies, 52% used preoperative ultrasound to determine the target volume to be implanted, 16% used preoperative computerized tomography (CT) scans, and 18% placed seeds with an open surgical technique. An additional 11% of studies placed seeds or needles under ultrasound guidance using interactive real-time dosimetry. The number and distribution of radioactive sources to be implanted or the method used to prescribe dose was determined using nomograms in 27% of studies, a least squares optimization technique in 11%, or not stated in 35%. In the remaining 26%, sources were described as either uniformly, differentially, or peripherally placed in the gland. To evaluate implant quality, 28% of studies calculated some type of dose-volume histogram, 21% calculated the matched peripheral dose, 19% the minimum peripheral dose, 14% used some type of CT-based qualitative review and, in 18% of studies, no implant quality evaluation was mentioned. Six studies correlated outcome with implant dose. One study showed an association of implant dose with the achievement of a PSA nadir < or = 0.5. Two studies showed an improvement in biochemical control with a D90 (dose to 90% of the prostate volume) of 120 to 140 Gy or higher, and 2 additional studies found an association of clinical outcome with implant dose. One study correlated implant quality with biopsy results. Of the articles, 33 discussed evaluable treatment results, but only 16 reported findings based upon pretreatment PSA and biochemical control. Three- to 5-year biochemical control rates ranged from 48% to 100% for pretreatment PSAs < or = 4, 55% to 90% for PSAs between 4 and 10, 30% to 89% for PSAs > 10, < or = 20 and < 10% to 100% for PSAs > 20. Due to substantial differences in patient selection criteria (e.g., median Gleason score, clinical stage, pretreatment PSA), number of patients treated, median follow-up, definitions of biochemical control, and time points for analysis, no single technique consistently produced superior results. CONCLUSIONS: Our comprehensive review of prostate cancer brachytherapy literature failed to identify an optimal treatment approach when studies were analyzed for treatment outcome based upon pretreatment PSA and biochemical control. Although several well-designed studies showed an improvement in outcome with total dose or implant quality, the numerous techniques for implantation and the varied and inconsistent methods to specify dose or evaluate implant quality suggest that standardized protocols should be developed to objectively evaluate this treatment approach. These protocols have recently been suggested and, when implemented, should significantly improve the reporting of treatment data and, ultimately, the efficacy of prostate brachytherapy.     

A prosthetic contact lens in the treatment of ocular manifestations of albinism

A patient with severe ocular albinism was fitted with a prosthetic soft contact lens which improved both photophobic symptoms and facial cosmesis.     

Normal deposition of brain iron in childhood and adolescence: MR imaging at 1.5 T

Magnetic resonance (MR) images of the brain in 285 patients between the ages of 2 and 25 years were retrospectively studied to determine the appearance of brain iron accumulation. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus were evaluated with long TR/TE (repetition time/echo time) spin-echo sequences and staged. All four regions in most patients were initially hyperintense compared with white matter (stage I) before becoming isointense (stage II) and subsequently hypointense (stage III). The globus pallidus was the first to reach stage III, the red nucleus and substantia nigra were next, and the dentate nucleus was last. In general, decreased signal intensity (stage III) was not seen in these regions in patients less than 10 years old; in most patients it was seen by age 25 years. The dentate nucleus decreased in signal intensity more slowly and inconsistently; only one-third of patients had reached stage III by age 25 years. The temporal sequence of normal iron deposition as detected with MR imaging is helpful not only in the diagnosis of known iron-deposition diseases but also in the detection of iron-related pathologic changes.     

Human brain tumor-associated urinary high molecular weight transforming growth factor: a high molecular weight form of epidermal growth factor

Urinary protein obtained from a patient with a highly malignant brain tumor (astrocytoma, grade IV) was adsorbed to trimethylsilyl controlled-pore glass beads and selectively eluted with acetonitrile to yield a high molecular weight (HMW) human transforming growth factor (hTGF). This HMW hTGF promoted clonogenic cell growth in soft agar and competed for membrane receptors with mouse epidermal growth factor. After surgical resection of the tumor, no HMW hTGF was found in urine. HMW hTGF generated a human EGF (hEGF) radioimmunoassay competitive binding curve similar to that of hEGF and parallel to that of a highly purified HMW form of hEGF previously reported to be present in trace concentrations in normal human urine. Both hEGF and HMW hEGF were clonogenic in soft agar, and their clonogenic activity as well as that of HMW hTGF was inhibited by anti-hEGF serum. Both HMW hTGF and HMW hEGF had 20 to 25% of the radioreceptor binding activity of hEGF. HMW hTGF purified from the pooled urine of several patients with malignant astrocytomas and HMW hEGF purified from normal control urine comigrated at Mr 33,000. Thus, HMW hTGF was indistinguishable from HMW hEGF in terms of apparent molecular size, epidermal growth factor receptor binding activity, epidermal growth factor immunoreactivity, and clonogenic activity. Urinary HMW hEGF/hTGF may be of tumor cell origin or may represent a response of normal host tissues to the tumor or its products.     

Urinary transforming growth factors in neoplasia: separation of 125I-labeled transforming growth factor-alpha from epidermal growth factor in human urine

Purified human epidermal growth factor (hEGF) from urine promotes anchorage-independent cell growth in soft agar medium. This growth is enhanced by transforming growth factor-beta (TGF-beta), and is specifically inhibited by hEGF antiserum. Transforming growth factors of the alpha type (TGF-alpha), potentially present in normal human urine or urine from tumor-bearing patients, also promote anchorage-independent cell growth and compete with EGF for membrane receptor binding. Consequently, TGF-alpha cannot be distinguished from urinary hEGF by these two functional assays. Therefore, a technique for separation of TGF-alpha and related peptides from urinary EGF based on biochemical characteristics would be useful. Radioiodination of characterized growth factors [mouse EGF (mEGF), hEGF, and rat TGF-alpha (rTGF-alpha)], which were then separately added to human urine, was used to evaluate a resolution scheme that separates TGF-alpha from the high level of background hEGF present in human urine. Commercially available methyl bonded microparticulate silica efficiently adsorbed the 125I-labeled mEGF, 125I-labeled hEGF, and 125I-labeled rTGF-alpha that were added to 24-h human urine samples. Fractional elution with acetonitrile (MeCN) of the adsorbed silica released approximately 70 to 80% of the 125I-labeled mEGF and 125I-labeled hEGF between 25 and 30% MeCN, and over 80% of the 125I-labeled rTGF-alpha between 15 and 25% MeCN, with retention after dialysis of less than 0.2 and 1.7% of the original urinary protein, respectively. Consequently, a single-step enrichment of about 400-fold for mEGF and hEGF, and 50-fold for rTGF-alpha were achieved rapidly. Subsequent Bio-Gel P-10 chromatography indicated that 125I-labeled mEGF and 125I-labeled hEGF eluted later than would be predicted on the basis of their reported molecular weight of approximately 6000, whereas 125I-labeled rTGF-alpha eluted from Bio-Gel P-10 at an approximate molecular weight of 8000 to 9000. 125I-labeled rTGF-alpha bound to carboxymethyl cellulose and eluted at a less acidic pH than did hEGF. On reverse phase high performance liquid chromatography using a linear gradient of 18 to 35% MeCN over 120 min, 125I-labeled rTGF-alpha was comparatively hydrophilic, eluting at 22% MeCN in contrast to the more hydrophobic 125I-labeled hEGF, which eluted at 27% MeCN. These observed biochemical differences between hEGF and TGF-alpha provide a rationale for resolution of these and perhaps other related putative transforming growth factors from bulk urine of tumor-bearing patients.