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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 127 records · Page 7Linked to original sources

Topical FK-506 prevents experimental corneal allograft rejection.

We evaluated the efficacy of topical cyclodextrin-encapsulated FK-506 in the prevention of experimental corneal allograft rejection. Two weeks after inducing corneal inflammation and neovascularization with 8-0 silk sutures, 23 albino rabbits received a unilateral 8-mm diameter central penetrating corneal allograft from pigmented donors. Rabbits were randomly assigned to no treatment (eight eyes), topical cyclodextrin four times daily for 28 days (seven eyes), or topical FK-506 0.3 mg/ml in a cyclodextrin suspension (eight eyes) four times daily for 28 days. Grafts were examined daily for degree of inflammation, neovascularization, edema, and signs of rejection for up to 100 days. Seven of eight (88%) untreated grafts and five of seven (71%) cyclodextrin-treated grafts rejected at a median of 3 weeks after transplantation, whereas only two (25%) of eight FK-506-treated grafts rejected and did so at a significantly longer interval (p < 0.005). Topical FK-506 prevents or delays corneal allograft rejection after experimental corneal transplantation.

Administration, Topical↗

Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma.

Specimens from 23 patients with enteropathy-associated T cell lymphoma were studied by immunohistochemistry after antigen retrieval. Specimens from 14 of these patients were investigated for the presence of clonal T cell gene rearrangements in both the tumor and the adjacent enteropathic intestine by the polymerase chain reaction. Primers for T cell receptor beta and gamma genes were used in a combination that permits the identification of approximately 90% of T cell receptor rearrangements. Clonal rearrangements of the T cell receptor were found in 13 of the 14 tumors studied. Specimens of enteropathic bowel resected with the tumor, but showing no morphological or immunohistochemical evidence of tumor involvement, showed clonal T cell receptor gene rearrangements in 11 cases. In 10 of these, the amplified DNA was of the same molecular weight in the enteropathic bowel as in the corresponding tumor. In 2 cases, sequencing the polymerase chain reaction product showed identical T cell receptor gene rearrangements in the tumor and in the adjacent intestine. Uniform staining for p53 was seen in 22 of the 23 tumors. In 9 of 19 cases studied, collections of small lymphocytes in the enteropathic bowel expressed p53. In all but one of these specimens, a clonal rearrangement of the T cell receptor genes was identified. We interpret these findings as support for the concept that enteropathy-associated T cell lymphoma arises on a background of gluten-sensitive enteropathy with evolution of neoplastic T cell clones from the reactive T cell population present in the enteropathic bowel.

Adult↗

Detection of specimen contamination in routine histopathology by HLA class II typing using the polymerase chain reaction and sequence specific oligonucleotide probing.

This study evaluates the use of human leukocyte antigen (HLA) class II PCR-SSO typing for the investigation of suspected specimen contamination in four routine surgical histopathology cases. Two cases were of patients undergoing transurethral resection of the prostate gland. The third case was a patient undergoing excision of a subcutaneous small cell carcinoma. The fourth case was a patient undergoing reversal of a Hartman's procedure for adenocarcinoma of the colon. Tissue was extracted from routinely processed formalin-fixed, paraffin-embedded material and HLA class II typed, using a non-radioactive polymerase chain reaction-sequence specific oligonucleotide probe technique (PCR-SSO), using probes specific for the DRB, DQA, and DQB loci. The accuracy of PCR-SSO typing of DNA extracted from paraffin biopsy material was confirmed by concordant results for DRB, DQA, and DQB typing in five separate control individuals from whom frozen and paraffin lymph node biopsies were available. PCR-SSO typing was also successful in the four study cases and revealed that contamination had occurred in two cases, eliminating this possibility in the remaining cases. This study demonstrates that DNA can be reliably amplified and accurately typed from routinely processed material, and reveals a useful new application for PCR-SSO tissue typing.

Adenocarcinoma↗

Pleomorphic fibrohistiocytoma of the breast: a potential pitfall in breast biopsy interpretation.

We describe a benign mammary mesenchymal tumour with atypical stromal giant cells in the contralateral breast of a 66-year-old woman with infiltrating ductal carcinoma. The clinical, morphological and immunohistochemical features of this tumour suggest a pleomorphic variant of fibrous histiocytoma. This benign lesion represents a possible pitfall in breast pathology when interpreting a frozen section or fine needle aspiration biopsy.

Aged↗

An evaluation of six new intrauterine devices.

A newer generation of IUDs that includes the Copper T-380A/Ag (TCu-380A/Ag) IUDs and the Multiload Copper-375 (MLCu375) IUDs has been developed and marketed. The high efficacy of these IUDs in preventing accidental pregnancies has been equated to that of oral contraceptives and even sterilization. However, the reduction of two other IUD-related pertinent events, namely, expulsion and medical removal due to bleeding and/or pain, has been less impressive. Therefore, efforts are continuing to develop new IUDs. In this paper, the authors review the physical structures of six new IUDs: the CU-SAFE, Cu-Fix, Ombrelle, Fincoid, and Multiload Mark II IUDs, and the intracervical fixing device (ICFD). The clinical performance of the first four devices is also evaluated. Independent, noncomparative studies suggest that all of the four new IUDs may perform as well as, or even better than, the TCu-380A IUD in terms of expulsions and medical removals attributable to bleeding and/or pain. However, we deem these results tentative, and emphasize the need for multi-center, randomized comparative clinical trials with larger sample sizes and long-term follow-up.

Evaluation Studies as Topic↗

Herpetic Eye Disease Study. A controlled trial of oral acyclovir for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of oral acyclovir in treating stromal keratitis caused by herpes simplex virus (HSV) in patients receiving concomitant topical corticosteroids and trifluridine. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter trial in 104 patients with HSV stromal keratitis without accompanying HSV epithelial keratitis. Sample size was chosen so that a 5%, one-tailed test would have an 80% chance of detecting a doubling of the median time to treatment failure. Patients were randomized to receive a 10-week course of either oral acyclovir (400 mg 5 times daily, n = 51) or placebo (n = 53). All patients also received a standard regimen of topical prednisolone phosphate and trifluridine. Ophthalmologic examinations were performed weekly during the 10-week treatment period, every 2 weeks for an additional 6 weeks, and at 6 months after entry into the trial. RESULTS: The median time to treatment failure (defined as worsening or no improvement of stromal keratitis or an adverse event) was 84 days (95% confidence interval, 69-93 days) for the acyclovir group and 62 days (95% confidence interval, 57-90 days) for the placebo group. By 16 weeks, 38 patients (75%) in the acyclovir group and 39 patients (74%) in the placebo group had failed treatment. Also by that time, the keratitis had resolved with trial medications, and there was no subsequent worsening in nine patients (18%) in the acyclovir group and ten (19%) in the placebo group. None of these results were significantly different between the two groups. However, visual acuity improved over 6 months in significantly more patients in the acyclovir group than in the placebo group. CONCLUSION: There was no statistically or clinically significant beneficial effect of oral acyclovir in treating HSV stromal keratitis in patients receiving concomitant topical corticosteroids and trifluridine with regard to time to treatment failure, proportion of patients who failed treatment, proportion of patients whose keratitis resolved, time to resolution, or 6-month best-corrected visual acuity. Visual acuity improved over 6 months in more patients in the acyclovir group than in the placebo group.

Acyclovir↗

Capnocytophaga keratitis. A clinicopathologic study of three patients, including electron microscopic observations.

BACKGROUND: Histopathologic studies of this unusual keratitis caused by Capnocytophaga species have not been reported previously. METHODS: The authors report the light microscopic and ultrastructural findings of three patients with a distinctive necrotizing keratitis caused by an anaerobic gram-negative bacillus. In three patients, ages 19, 81, and 91 years, a necrotizing stromal keratitis developed; two of these patients had a previous penetrating keratoplasty for pseudophakic bullous keratopathy. The first patient did not have ocular surgery previously and was treated initially for presumed Acanthamoeba keratitis. RESULTS: By light microscopy, all three keratectomy specimens were strikingly similar and showed a necrotizing and/or suppurative stromal keratitis displaying myriad slender, fusiform, gram-negative bacilli located anterior to Descemet's membrane and extending into the deep corneal stroma, assuming a "picket fence" appearance. Cultures of the cornea in case 1 grew Capnocytophaga ochracea. For the remaining two patients, a diagnosis presumptively was made based on characteristic histopathologic features. Results of electron microscopic examination showed numerous bacilli that were mostly extracellular; occasional organisms were phagocytosed by macrophages. CONCLUSION: The histopathologic features of Capnocytophaga keratitis are unique; therefore, a presumptive diagnosis can be made based on the morphology and location of the bacilli in the keratectomy specimens. To the authors' knowledge, this is the first study describing the typical histopathologic and electron microscopic findings of Capnocytophaga keratitis.

Adult↗

Herpetic Eye Disease Study. A controlled trial of topical corticosteroids for herpes simplex stromal keratitis.

PURPOSE: To evaluate the efficacy of topical corticosteroids in treating herpes simplex stromal keratitis. METHODS: The authors performed a randomized, double-masked, placebo-controlled, multicenter clinical trial of 106 patients with active herpes simplex stromal keratitis who had not received any corticosteroids for at least 10 days before study enrollment. Patients were assigned to the placebo group (n = 49) or the steroid group (topical prednisolone phosphate; n = 57); both regimens were tapered over 10 weeks. Both groups received topical trifluridine. Visual acuity assessment and slit-lamp biomicroscopy were performed weekly for 10 weeks, every other week for an additional 6 weeks or until removal from the trial, and at 6 months after randomization. RESULTS: The time to treatment failure (defined by specific criteria as persistent or progressive stromal keratouveitis or an adverse event) was significantly longer in the steroid group compared with the placebo group. Compared with placebo, corticosteroid therapy reduced the risk of persistent or progressive stromal keratouveitis by 68%. The time from randomization to resolution of stromal keratitis and uveitis was significantly shorter in the steroid group compared with the placebo group even though both groups included patients who were removed from the study and treated with topical corticosteroids according to best medical judgment. Nineteen (33%) of the steroid-treated patients and 11 (22%) of the placebo-treated patients completed the 10 weeks of protocol therapy and had stable, noninflamed corneas after 16 weeks. At 6 months after randomization, no clinically or statistically significant differences in visual outcome or recurrent herpetic eye disease were identified between the steroid and placebo groups. CONCLUSIONS: The topical corticosteroid regimen used in this study was significantly better than placebo in reducing persistence or progression of stromal inflammation and in shortening the duration of herpes simplex stromal keratitis. Postponing steroids during careful observation for a few weeks delayed resolution of stromal keratitis but had no detrimental effect as assessed by visual outcome at 6 months.

Administration, Topical↗

Infectious crystalline keratopathy due to Streptococcus pneumoniae. Possible association with serotype.

BACKGROUND: Infectious crystalline keratopathy is a distinctive clinical entity characterized by bacterial replication within the corena without inflammation. The authors report on a patient with infectious crystalline keratopathy due to Streptococcus pneumoniae serotype 11F. They used this isolate to study the contribution of the pneumococcal polysaccharide capsule to the pathogenesis of the infectious crystalline keratopathy. METHODS: Aliquots containing 10(6) colony-forming units of pneumococci serotype 11F, serogroup 9 or 15, were inoculated into New Zealand white rabbit corneas. The corneas were examined at 24, 48, and 72 hours. Representative corneas were excised at 24 hours and processed for histopathologic analysis. RESULTS: Pauci-inflammatory crystalline lesions developed in all corneas inoculated with the serotype 11F ocular isolate by 24 hours. Suppurative keratitis developed in control corneas inoculated with serogroup 9 or 15 pneumococci. The nonocular 11F isolates produced lesions with some features compatible with infectious crystalline keratopathy. CONCLUSION: Different pneumococcal serotypes vary in their ability to produce infectious crystalline keratopathy. Because serotype differences reflect differences in the antigenic polysaccharides of the bacterial capsule, this study suggests that properties of the pneumococcal capsule may influence the initial development of infectious crystalline keratopathy.

Aged↗

Incidence, risk factors, and prevention of poststerilization regret in women: an updated international review from an epidemiological perspective.

Tubal sterilization is the world's most commonly used contraceptive method. Even a small proportion of women incurring poststerilization regret would translate into a large number of sufferers. In this review, we examine recent reports on the incidence of, and the risk factors for, posttubal sterilization regret in women and requests for sterilization reversal in both developed countries and less-developed countries. We also consider the implications of our findings in the practical prevention of poststerilization regret and requests for sterilization reversal, and discuss methodological issues.

Adult↗

Extramedullary haemopoiesis in fetal and adult human spleen: a quantitative immunohistological study.

Haemopoietic cells were assessed in spleens from normal adults, adults with splenic extramedullary haemopoiesis due to chronic myeloproliferative disorders and fetuses of 17-21 weeks' gestation. A variety of antigens expressed by developing granulocytes and erythrocytes were demonstrated immunohistochemically. The relative proportions of early and late precursor cells of these two lineages were quantified. There was no significant haemopoiesis in normal adult spleen, while there was abundant (predominantly granulocytic) haemopoiesis in patients with chronic myeloproliferative disorders. Fetal spleens contained numerous late erythroid precursors but few early erythroid or granulocytic cells. The relative numbers of early and late haemopoietic cells in adult chronic myeloproliferative disorders and fetal spleens showed statistically significant differences. Our findings indicate that haemopoiesis in the spleens of adult patients with these disorders differs fundamentally from that occurring in fetal life. They support the view that the human spleen does not have a significant role in fetal haemopoiesis, but that it filters circulating nucleated erythroid precursors and is permissive of their terminal differentiation only. Our results also favour the view that adult splenic haemopoiesis originates by displacement of precursor cells from the bone marrow rather than by activation of stem cells which have lain dormant in the spleen since fetal life.

Adult↗

Microwave antigen retrieval in immunocytochemistry: a study of 80 antibodies.

AIMS: To evaluate the effect of microwave irradiation on the staining quality of a range of commonly used primary antibodies in archival, formalin fixed, paraffin wax embedded material, with emphasis on antibodies that have previously worked successfully only on frozen tissue. METHODS: Immunocytochemistry (streptavidin-biotin complex technique) was performed on histological sections of a range of normal and pathological tissues, after varying treatment with microwave irradiation. The staining quality of each antibody was compared with that achieved without prior treatment of the sections or after enzyme predigestion. RESULTS: Microwave irradiation permitted successful immunostaining with 20 antibodies that stained only frozen tissues before. The staining characteristics of 21 antibodies that were already known to stain formalin fixed, paraffin wax embedded material were improved. Another 39 antibodies did not show enhanced staining with microwave irradiation. The method preserves tissue morphology and produces more consistent staining than that achieved by enzyme predigestion with many antibodies. Microwave irradiation may also allow some primary antibodies to be used at higher working dilutions. The citrate buffer used in this study avoids the necessity of exposure to heavy metal salts. CONCLUSIONS: Microwave antigen retrieval represents an important technical advance within immunocytochemistry that will greatly increase the range of antibodies which can be used to study formalin fixed, paraffin wax embedded tissues.

Antibodies, Monoclonal↗

Transepithelial phosphate transport in rabbit proximal tubular cells adapted to phosphate deprivation.

Both renal and nonrenal cells in culture adapt to deprivation of Pi by increasing Na-dependent Pi uptake. We studied whether this change in uptake is reflected in an increased renal transepithelial Pi transport. We grew primary cultures of rabbit renal cortical cells in plastic flasks and subcultured them onto Millicell-HA filters. This produced cell monolayers, which structurally and functionally resembled proximal tubule. These cells performed Na-dependent net transepithelial transport of 32Pi in the apical-to-basolateral direction that was inhibited by phosphonoformic acid in the apical fluid or by ouabain in the basolateral fluid or by preincubation with parathyroid hormone. Overnight incubation at low Pi concentrations led to a progressive increase in 5-min Na-dependent Pi uptake into cell monolayers. Na-dependent Pi uptake was threefold higher following overnight incubation at 25 microM Pi, compared with 3 mM Pi, and the increase was one-half maximal with incubation at an extracellular Pi concentration ([Pi]) of 300 microM. This was associated with a decrease in Na-dependent transepithelial Pi flux to the basolateral fluid by the same cells, which fell dramatically following incubation at < or = 300 microM Pi. There was no change in Na-dependent uptake or transepithelial transport of L-glutamine. This adaptation to Pi deprivation in vitro appears to serve to restore depleted cell stores of Pi rather than to regulate transepithelial Pi transport.

Adaptation, Physiological↗