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Biomedical subjects

D B Jones

Publications and source records attributed to D B Jones.

At least 19 recordsLinked to original sources

Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt's lymphoma.

Epstein-Barr virus (EBV)-infected cells may sustain three distinct forms of virus latency. In lymphoblastoid cell lines, six EBV-encoded nuclear antigens (EBNA1, 2, 3A, 3B, 3C, -LP), three latent membrane proteins (LMP1, 2A, 2B), and two nuclear RNAs (EBERs) are expressed. This form of latency, termed latency III, is also encountered in some posttransplant lymphoproliferative disorders. In EBV-positive cases of Hodgkin's disease, the EBERs, EBNA1, and the LMPs are expressed (latency II), whereas in Burkitt's lymphoma (BL) only the EBERs and EBNA1 have been detected (latency I). We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology. Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases. Also, the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases, indicating entry into the lytic cycle. A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines. Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors.

Adolescent

The influence of intraoperative gallbladder perforation on long-term outcome after laparoscopic cholecystectomy.

During laparoscopic cholecystectomy, gallbladder perforation with leakage of bile and/or gallstones into the abdominal cavity occurs frequently. When this occurs, our practice has been to lavage the operative field and retrieve as many gallstones as possible. We were concerned, however, that complications secondary to infection or adhesions might develop. To address this issue, our first 250 consecutive patients undergoing laparoscopic cholecystectomy were surveyed by postal questionnaire. In the 35-48 months (mean, 41 months) since operation, six patients (2.6%) died of nonbiliary causes. Of the 225 patients (90%) who completed the questionnaire, 73 (33%) suffered intraoperative gallbladder perforation. There were no late wound or intraabdominal infectious complications and no patient has required reoperation for intraabdominal sepsis or bowel obstruction. In the entire group, gastrointestinal symptoms were prevalent and included flatulence (40%), loose stools or fecal urgency (35%), belching (23%), and nausea (4%). The prevalence of these complaints was similar in patients with and without gallbladder perforation. Intraoperative gallbladder perforation during laparoscopic cholecystectomy, therefore, does not cause adverse long-term complications when accompanied by operative lavage and stone removal.

Adolescent

Sutured or fibrin-glued laparoscopic choledochojejunostomy.

Minimally invasive techniques for choledochojejunostomy offer theoretical advantages for palliating unresectable periampullary neoplasms. Fibrin glue, a biologic adhesive containing concentrated fibrinogen, may obviate suturing and promote healing without stricture formation. We examined the technical ability to perform laparoscopic choledochojejunostomy (LCJ) and the applicability of thrombin-activated fibrin glue in an animal model of biliary obstruction. Domestic pigs underwent laparoscopic cholecystectomy and ligation of the distal bile duct. Three days later, a side-to-side LCJ was performed by intracorporeal sutured anastomosis (n = 7) or using four stay sutures and homologous fibrin glue (n = 7). Control animals underwent a similar bypass via open laparotomy (n = 7). The postoperative interval to ambulation and oral intake was recorded, and serial serum liver enzymes were measured. The animals were sacrificed at 6 weeks, and tensile strength of the anastomoses was assessed by tensometry. Liver function tests returned to normal values within 7 days following all methods of choledochojejunostomy. In the fibrin glue group, three anastomotic leaks (43%) occurred in the 1st postoperative week. At 6 weeks, all other anastomoses were intact and patent by cholangiogram, but there was moderate stenosis of two open and one fibrin-glue anastomosis. The sutured LCJ, while taking approximately 1 h longer to perform (P < 0.05), resulted in similar efficacy and more rapid recovery (P < 0.05) than open biliary-enteric bypass. Fibrin-glued LCJ was performed rapidly, but had less tensile strength (P < 0.05) and often leaked in the early post-operative interval. We conclude that while there may be a role for laser-activated solders for primary anastomosis, thrombin-activated fibrinogen cannot be advocated as the primary means of creating biliary anastomoses. Using intracorporeal suturing techniques, laparoscopic choledochojejunostomy may be performed safely.

Alanine Transaminase

Impact of pneumoperitoneum on trocar site implantation of colon cancer in hamster model.

BACKGROUND: Numerous anecdotal reports have documented the spread of colon cancer to trocar sites after laparoscopic-assisted colectomy. We hypothesized that the pneumoperitoneum of laparoscopy potentiated tumor adherence to trocar sites. PURPOSE: This study was designed to determine the effect of CO2 pneumoperitoneum on the rate of tumor implantation at trocar sites. METHODS: Viable GW-39 human colon cancer cells were injected into the abdominal cavity of hamsters (2 x 10(6) cells/hamster). A midline laparotomy, insertion of four 5-mm trocars, injection of viable cells into the mesentery of the cecum, and free peritoneal cavity was performed in two groups: one control group (41) who did not receive a pneumoperitoneum and a comparison group (50) who underwent pneumoperitoneum for ten minutes at an insufflation pressure of 10 mmHg. Animals were killed at six weeks, and hematoxylin and eosin-stained sections of trocar wounds, midline wound, small intestine, cecum, liver, and lung were examined by a veterinary pathologist, who was blinded to operation. RESULTS: Pneumoperitoneum increased tumor implantation in the cecal mesentery and the midline incision (P < 0.05) but did not effect recurrence in the liver, lung, or jejunum. Trocar site implantation tripled with the addition of pneumoperitoneum increased implantation of pneumoperitoneum (26 vs. 75 percent) (P < 0.0001). CONCLUSION: Pneumoperitoneum increased implantation of free intra-abdominal cancer cells at wound sites on the abdominal wall or within the abdominal cavity in this animal model. The use of pneumoperitoneum during laparoscopy in patients with colon cancer should only be performed in a protocol setting to evaluate the effect of pneumoperitoneum on the treatment of cancer.

Animals

HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy.

CD is a gluten-sensitive enteropathy, strongly associated with expression of the DQA1*0501, DQB1*0201 genotype. CD patients have an increased risk of malignancy, particularly EATCL. However, it is controversial as to whether adults with EATCL represent a subgroup of patients with CD or should be regarded as a distinct entity. To investigate the genetic relationship between CD and EATCL, HLA class II DRB1, DQA1, and DQB1 typing of peripheral blood, frozen or paraffin-embedded biopsy tissue obtained from Caucasian patients with CD (n = 91) or EATCL (n = 47) was performed by PCR-SSOP typing. Genotype frequencies were compared with those observed in 151 unrelated control individuals. A total of 83 (91%) of 91 CD patients were of DQA1*0501, DQB1*0201 genotype (pc < 10(-6), RR = 522.2), compared with 40 (93%) of 43 EATCL patients (pc < 10(-6), RR = 44.2) with amplifiable DNA versus 35 (23%) of 151 controls. DRB1*03 frequencies were also elevated in both patient groups (79 of 91 in CD [87%; pc < 10(-6), RR = 24.5] and 38 of 40 in EATCL [95%; pc < 10(-6), RR = 70.7]) compared with controls (32 of 151, 21%). These results confirm previous studies of HLA associations in CD and also suggest that EATCL arises in individuals with the DQA1*0501, DQB1*0201 CD-predisposing genotype. However, the frequency of DRB1*03,04 heterozygotes was significantly increased in the EATCL group (16 of 40, 40%) compared with both control individuals (3 of 151, 2%; pc < 10(-6), RR = 32.9) and uncomplicated CD patients (6 of 91, 7%; pc = 0.04, RR = 9.4).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Corneal lipidosis in patients with the acquired immunodeficiency syndrome.

PURPOSE: Certain drugs bind to anionic phospholipids of lysosomal membranes and produce progressive intracellular accumulation of lamellar inclusions. We studied two patients treated for opportunistic infections associated with the acquired immunodeficiency syndrome (AIDS), who developed bilateral ocular surface changes suggestive of drug-induced corneal lipidosis. METHODS: Two patients with AIDS had translucent vacuoles within the corneal epithelium and mild conjunctival hyperemia. Because the differential diagnosis included microsporidial keratoconjunctivitis, biopsies of the ocular surface were performed for histopathologic analysis. RESULTS: Transmission electron microscopy of corneal epithelial debridement and conjunctival biopsy specimens showed intracellular, electron-dense lipoidal bodies and multilaminated lysosomal inclusions suggestive of a drug-induced lipidosis. Both patients also had tubuloreticular inclusions in conjunctival capillary endothelial cells. The ocular surface changes resolved within one to three months after dosage reduction or discontinuation of systemic ganciclovir and acyclovir. CONCLUSIONS: Drug-induced phospholipidosis is a cause of punctate corneal epitheliopathy during AIDS, but the responsible agent remains to be identified.

AIDS-Related Opportunistic Infections

Results of a change to routine fluorocholangiography during laparoscopic cholecystectomy.

BACKGROUND: Early in our experience with laparoscopic cholecystectomy (LC), intraoperative cholangiography (IOC) was performed selectively with static imaging techniques. We subsequently changed to routine digital fluorocholangiography (FIOC) and evaluated the results of this strategy. METHODS: In a consecutive series of 356 LCs, 11 patients (3%) were converted to open cholecystectomy. In the remaining 345 patients FIOC was attempted in 336 patients (97%) and was successfully completed in 328 patients (95%). Results of IOC and outcomes were compared prospectively in patients without indications for IOC (group I, n = 185) with those with criteria for selective IOC (group 2, n = 160) and retrospectively with patients without indications for IOC undergoing static IOC (group 3, n = 56). RESULTS: Time to perform FIOC was less than for static IOC (14 +/- 1 versus 24 +/- 1 minutes, p < 0.001). Aberrant ductal anatomy was appreciated by using FIOC in 11% but affected operative management in only 3% of patients. Choledocholithiasis was detected in 23 patients (7%) undergoing FIOC; only two of these patients with stones were in Group 1. Duct stones discovered by IOC were cleared laparoscopically in 89% of those attempted (73% of all patients). Neither morbidity nor duct injury caused by FIOC was noted. CONCLUSIONS: FIOC is much more rapid to perform than static IOC. Digital fluoroscopy is accurate and safe and permits rapid evaluation and management of bile duct stones. Selective use of FIOC efficiently assesses the common duct in the era of LC.

Cholangiography

Immunohistochemical characterization of intact stromal layers in long-term cultures of human bone marrow.

We have performed an immunohistochemical study of intact adherent layers of human long-term bone marrow cultures (hLTBMC) in order to characterize the cell types present. Our panel of antibodies was selected to demonstrate various mesenchymal and haemopoietically derived cell types and to assess the presence of molecules of potential importance as adhesive ligands between haemopoietic cells and stroma. Subpopulations of fibroblasts and macrophages were identified which differed in immunophenotype. We were able to demonstrate modulation of fibroblast and extra-cellular matrix immunophenotypes between 2 and 12 weeks in culture. Stromal cells and matrix expressed a wide variety of antigens of potential importance in haemopoietic cell adhesion, but no ICAM-1, 2 or 3 could be demonstrated to correspond to the strong LFA-1 expression seen in haemopoietic precursor cells. No localization of antigen expression by stromal elements was found to account for the formation of haemopoietic foci at particular sites. However, granulocyte-predominant foci preferentially occupied the interstices and margins of structures which appeared to be vascular arrays.

Bone Marrow Cells

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