Search PubMed⌕ Search

Biomedical subjects

J Pfeifer

Publications and source records attributed to J Pfeifer.

At least 37 records · Page 2Linked to original sources

Bacterial antigen delivery systems: phagocytic processing of bacterial antigens for MHC-I and MHC-II presentation to T cells.

Using an in vitro model system we have studied parameters of both bacteria and antigen presenting cells that influence peptide presentation by murine major histocompatibility complex class II (MHC-II) and class I (MHC-I) molecules. To study MHC-II presentation, the HEL (52-61) epitope, which binds the murine MHC-II molecule I-Ak, was expressed as the cytoplasmic Crl-HEL fusion protein in S. typhimurium. When murine peritoneal macrophages mediated phagocytic processing of S. typhimurium expressing Crl-HEL, HEL (52-61) was processed and presented on I-Ak more efficiently from heat-killed S. typhimurium than from viable bacteria, and from a rough LPS strain compared to its isogenic smooth LPS counterpart, most likely due to enhanced phagocytosis of the rough LPS strain. Macrophages also processed phoP S. typhimurium strains with greater efficiency for peptide presentation by I-Ak than wild type bacteria while Salmonella constitutively expressing phoP were processed for peptide presentation by I-Ak less efficiently than wild type Salmonella. We have also shown that macrophage phagocytosis of E. coli or S. typhimurium results in presentation of bacterial antigens by MHC-I molecules. To investigate the role of post-Golgi MHC-I molecules in this presentation pathway, peritoneal macrophages from TAP1-/- mice, which are deficient in presenting endogenous antigens on MHC-I and lack significant surface MHC-I expression, were co-incubated with bacteria containing the 257-264 epitope from ovalbumin [OVA(257-264)], which binds the murine class I molecule Kb. Peritoneal macrophages from TAP1-/-/ mice could process bacteria expressing the OVA epitope for recognition by epitope-specific T hybridoma cells. This processing and presentation was reduced in efficiency between three to 100 fold compared to C57BL/6 macrophages, depending on the protein harbouring the OVA (257-264) epitope (Crl-OVA or native OVA). This suggests that the protein context of the OVA (257-264) epitope influences the extent of TAP-independent processing for MHC-I presentation. In addition, we show that murine bone marrow-derived dendritic cells can phagocytose and process viable gram negative bacteria for peptide presentation on MHC-I and MHC-II; inhibition studies showed that acidic compartments in dendritic cells are required for this presentation. These results suggest that dendritic cells may be potential antigen presenting cells used in eliciting specific immune responses against bacteria.

Animals↗

Physiological and clinical outcome of anterior sphincteroplasty.

A total of 55 women underwent sphincteroplasty for the treatment of faecal incontinence related to anterior defects. Patients were followed prospectively for a mean of 29 months to evaluate the outcome overall and according to age. All patients were evaluated clinically by means of a questionnaire and graded using an incontinence scoring system ranging from 0 (perfect continence) to 20 (complete incontinence). Some 52 patients (95 per cent) had had a previous vaginal delivery and 30 (55 per cent) had a history of previous anal sphincter repair. Physiological and functional parameters in patients with a successful outcome (n = 39) were compared with those in patients with a poor outcome (n = 16). The results were also compared in patients under (n = 39) and over (n = 16) 60 years of age. Overall, patients with a successful outcome had a significant change in mean and maximal resting and squeeze pressures. These changes correlated well with the increase in the high-pressure zone (HPZ) length from 1.0-2.2 cm (P = 0.0002) and with functional outcome (change in incontinence score from 15.3 to 5.8; P < 0.0001). In patients over 60 years of age, a significant change in mean squeeze pressure (P = 0.03) and HPZ length (P = 0.01) was noted and correlated with functional outcome (change in incontinence score from 14.3 to 6.4; P < 0.0001). A successful outcome after anterior sphincteroplasty is related to improvement in sphincter function even in an older population. These results demonstrate that age itself does not seem to be a predictor of poor outcome. Patients should not be denied a repair exclusively on grounds of age.

Adult↗

Laparoscopic colorectal surgery: analysis of 140 cases.

BACKGROUND: This study was performed to prospectively assess the results of our first 140 consecutive patients who underwent laparoscopic or laparoscopic-assisted colorectal operations. METHODS: The parameters studied included the type and length of procedure, intra- and postoperative complications, conversion to open surgery, and length of ileus and hospitalization. RESULTS: 140 laparoscopic and laparoscopic-assisted procedures were performed between May 1991 and January 1995. The mean patient age was 48 (range 12-88) years; there were 78 males and 62 females. Indications for surgery included inflammatory bowel disease in 47, colorectal carcinoma in 19, diverticular disease in 17, polyps in 16, familial polyposis in 7, colonic inertia in 7, fecal incontinence in 11, sigmoidocele in 3, irradiation proctitis in 3, rectal prolapse in 2, intestinal lymphoma in 2, and miscellaneous conditions in 6. The procedures included 38 total abdominal colectomies (TAC) (ileoanal reservoir 28, ileorectal anastomosis 8 and end ileostomy 2); 70 segmental resections of the colon, small bowel, and rectum; 18 diverting stoma creations; 10 reversal of Hartmann's procedures; and 4 other procedures. In 15 cases, the laparoscopic procedure was converted to a laparotomy (11%); 31 patients (22%) sustained 37 complications, which included: enterotomies(7), hemorrhage(10), intraabdominal abscess(4), prolonged ileus(6), wound infection(4), intestinal obstruction(2), anastomotic leak(1), aspiration(1), cardiac arrhythmia(1), and upper intestinal bleeding(1); there was no mortality. The overall complication rate in TAC cases was significantly higher (42%) when compared to that of all other procedures (segmental resection 17%, others 9%), P < 0.05. The mean length of operating time was 4 (range 2.5-6.5) h for TAC, 2.6 (range 1.5-5.5) h for segmental colonic resections, and 1.7 (range 0.7-4) for all other procedures. The length of ileus was 3.5 (range 2-7) days after TAC, 3 (range 2-7) after the segmental resections and 2 (range 1-4) after the other procedures. The mean length of hospital stay was 6.8 (2-40) days (8.4, 6.5, and 6.3 days for the TAC, segmental resections, and other procedures, respectively). CONCLUSION: The feasibility of laparoscopic colorectal surgery has been well established. TAC is associated with a higher complication rate compared to other laparoscopic colorectal procedures.

Adolescent↗

Defecography and proctography. Results of 744 patients.

PURPOSE: Radiographic imaging of dynamic changes within the pelvic cavity and rectum during evacuation has been recognized as a valuable method of assessment. This study was designed to assess the incidence and clinical significance of defecographic findings in patients with possible evacuation disorders. MATERIALS AND METHODS: All defecographic studies were reviewed by a single colorectal surgeon familiar with patients' histories and physical findings. RESULTS: Between July 1988 and July 1995, 744 patients (566 females and 178 males) with a mean age of 63.5 (range, 12-95) years had defecographic and proctographic examination. Four hundred forty-six (60 percent) patients were diagnosed who complained of constipation, 123 (16.5 percent) of fecal incontinence, 42 (5.6 percent) of rectal prolapse, 82 (11 percent) of rectal pain, and 51 (6.9 percent) had a combination of more than one of these diagnoses. Although 93 (12.5 percent) of these evaluations were considered normal, 61 (8 percent) revealed rectal prolapse, 191 (25.7 percent) rectocele, 82 (11 percent) sigmoidocele, and 94 (12.6 percent) intussusception; in 223 (30 percent) patients, a combination of these findings was noted. Patients with paradoxical puborectalis contraction had an extremely high frequency of constipation compared with other symptoms (P < 0.0001). CONCLUSIONS: Defecography can reveal abnormalities in the majority of patients with evacuatory disorders. There was a high incidence of rectocele, sigmoidocele, and intussusception. Care must be taken not to treat patients strictly based on radiographic findings.

Aged↗

Surgery for constipation: a review.

PURPOSE: Constipation is related to intestinal motility disorders (colonic inertia (CI)), pelvic floor disturbances (pelvic outlet obstruction), or a combination of both problems. This review summarizes the physiologic and pathophysiologic changes in patients with intractable constipation and gives an overview of surgical treatment options. RESULTS: Although subtotal colectomy with ileorectal anastomosis is the best surgery for CI, there are still approximately 10 percent of patients who will complain of pain and constipation. A completion proctectomy and an ileoanal pouch procedure may be a viable option in a highly select group of patients. In patients with megabowel, reported results are mixed. Subtotal colectomy, partial colectomy for megacolon, and the Duhamel procedure for megarectum have all been reported with variable results. In patients with an isolated distended sigmoid colon, sigmoid colectomy has achieved good results. Anorectal myectomy has not been proven to be successful in the long term. However, in patients with adult short segment Hirschsprung's disease, myectomy can be successful. Patients with pelvic outlet obstruction can be successfully treated with biofeedback. In a small group of patients with a rectocele or a third degree sigmoidocele, surgical intervention yields a high success rate. Division or resection of the puborectalis muscle is not recommended. In patients with a mixed pattern of CI and pelvic outlet obstruction, surgical intervention alone is often not successful. These patients achieve better results by conservative treatment of pelvic outlet obstruction, followed by a colectomy. CONCLUSION: Surgical intervention for patients with intractable constipation is rarely necessary. However, thorough preoperative physiologic testing is mandatory for a successful outcome.

Adult↗

A constipation scoring system to simplify evaluation and management of constipated patients.

PURPOSE: Constipation is a common complaint; however, clinical presentation varies with each individual. The aim of this study was to assess a standard scoring system for evaluation of constipated patients. MATERIALS AND METHODS: All consecutive patients with idiopathic constipation who were referred for anorectal physiologic testing were assessed. A subjective constipation score was calculated based on a detailed questionnaire that included over 100 constipation-related symptoms. Based on the questionnaire, scores ranged from 0 to 30, with 0 indicating normal and 30 indicating severe constipation. The constipation score was then compared with the objective findings of the physiology tests, which include colonic transit time (CTT), anal manometry (AM), cinedefecography (CD), and electromyography (EMG). Colonic inertia was defined as diffuse marker delay on CTT without evidence of paradoxical contraction on AM, CD, or EMG. Pelvic outlet obstruction was defined as paradoxical puborectalis contraction, rectal prolapse or rectoanal intussusception, rectocele, or sigmoidocele. RESULTS: A total of 232 patients (185 females and 47 males) of a mean age of 64.9 (range, 14-92) years were evaluated. All patients had a score of more than 15; on evaluation of the significance of different symptoms in the constipation score with the Pearson's linear correlation test, 8 of 18 factors were identified as significant (P < 0.05). These factors included frequency of bowel movements, painful evacuation, incomplete evacuation, abdominal pain, length of time per attempt, assistance for evacuation, unsuccessful attempts for evacuation per 24 hours, and duration of constipation. All 232 patients had objective obstruction attributable to one or more of the following causes: paradoxical puborectalis contraction (81), significant rectocele or sigmoidocele (48), rectoanal intussusception (64), and rectal prolapse (9). CONCLUSION: The proposed constipation scoring system correlated well with objective physiologic findings in constipated patients to allow uniformity in assessment of the severity of constipation.

Adolescent↗

Hemostatic methods for the management of spleen and liver injuries.

The spleen and liver are the most frequently injured organs during blunt and penetrating abdominal trauma. Emergency laparotomy is crucial for early control of bleeding and to prevent "secondary" injury as a result of physiologic splanchnic vasoconstriction and free oxygen radicals. Altogether 98 patients with spleen and liver injuries were treated over an 8-year period. Primary orthotopic spleen preservation could be achieved in 46 of 63 patients. In 58 patients with hepatic trauma, hemostatic treatment was chosen based on the severity of the injury. Nonoperative management was used for four splenic and seven hepatic trauma patients. The most commonly used techniques were fibrin sealing, suturing, and débridement for hepatic injury and mesh splenorrhaphy, fibrin glue, and partial resection with a TA stapler for splenic injury. The death of patients with complex injuries was mainly due to preclinical massive blood loss and multiple organ failure.

Hemostatic Techniques↗

Laparoscopic surgery in the management of inflammatory bowel disease.

BACKGROUND: The role of laparoscopic surgery in the treatment of various upper and lower gastrointestinal disorders is still under investigation. However, a variety of laparoscopic procedures may be applied in the treatment of inflammatory bowel disease (IBD). PATIENTS AND METHODS: We present our initial results of laparoscopic and laparoscopic-assisted management of IBD in 72 consecutive patients (37 women and 35 men; mean age 36 years, range 20 to 79). The indications for surgery included: terminal ileitis in 29 patients, mucosal ulcerative colitis in 23 patients, Crohn's colitis in 11 patients, severe perianal Crohn's disease in 4 patients, duodenal Crohn's disease in 3 patients, Crohn's rectovaginal fistula in 1 patient, and rectourethral fistula in 1 patient. The procedures performed included: total abdominal colectomy (TAC) in 30 patients (22 with total proctocolectomy with ileoanal reservoir, 6 with TAC with ileorectal anastomosis, and 2 with TAC with end ileostomy), ileocolic resection in 30 patients, diverting loop ileostomy in 6 patients, closure of an end ileostomy as an ileorectal anastomosis in 3 patients who already underwent a TAC with end ileostomy, and duodenal bypass gastrojejunostomy in 3 patients. RESULTS: There were 16 complications in 13 (18%) patients: 3 enterotomies, 4 episodes of bleeding, 3 pelvic abscesses, 2 intestinal obstructions, 2 prolonged ileus, 1 anastomotic leak, and 1 efferent loop obstruction after gastrojejunostomy. However, only 3 patients required laparotomy for morbidity, and there was no mortality. In 7 (10%) patients, the laparoscopic procedure was converted to a laparotomy due to a large inflammatory mass with fistula in 4 patients, bleeding in 2 patients, and an enterotomy in 1 patient. The mean operating time was 2.9 hours (range 0.7 to 6) and the mean length of hospital stay was 6.5 days (range 3 to 19). When compared with ileocolic resection, total colectomy was associated with higher morbidity (30% versus 10%, P < 0.05) and longer hospitalization (8.7 days [range 4 to 19] versus 5.2 days [range 3 to 7], respectively; P < 0.05). CONCLUSIONS: According to this initial experience, laparoscopic surgery is a versatile and effective modality in the surgical management of inflammatory bowel disease in selected patients. However, laparoscopic total colectomy is associated with higher morbidity when compared with ileocolic resection.

Adult↗

Semi-automated PCR method for quantitating MDR1 expression.

The MDR1 gene is involved in drug resistance in many hematopoietic and solid tumors. The Quantitative PCR System 5000 (QPCR-5000; Perkin-Elmer) is a new instrument system that uses electrochemiluminescence to automatically quantitate polymerase chain reaction (PCR) products. A comparative study between radioactively labeled PCR (32P-PCR) and QPCR was performed to analyze the MDR1 gene expression in the drug-resistant (Doxorubicin) cell lines Dox40, Dox6, the parental cell line 8226/S, CEM Dox1 and three acute myeloid leukemia (AML) patient samples. Using the Dox40 and Dox6 resistant cell lines, we compared the sensitivities of QPCR and 32P-PCR. A strong signal was obtained from QPCR at 20 to 25 cycles (which is in the linear range for quantitation), while a weak signal was obtained using 32P-PCR at the same cycle number. Dilution experiments gave better precision with the QPCR than with the radioactive method. AML samples were studied with the MDR1-specific MAbs MRK16 and 4E3, and the efflux function was analyzed using Rh-123 retention in the absence or presence of verapamil. The three samples showed high (D = 0.79), medium (D = 0.52) and negative (D = 0.08) p-glycoprotein (P-gp) levels and correlated with efflux function. The MDR1/beta 2-M mRNA ratios for 32P-PCR were 0.41, 0.40 and 0.12, respectively, and were 0.127, 0.097 and 0.028, respectively, for QPCR. There were significant differences between the samples with high and medium P-gp levels comparing the two methods. Very low levels of MDR1 in CEM Dox1 cells could be detected only by QPCR. In conclusion, QPCR was found to be more reproducible, accurate and sensitive than 32P-PCR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Nonoperative management of splenic and hepatic trauma in the multiply injured pediatric and adolescent patient.

OBJECTIVE: To determine whether nonoperative management of splenic and hepatic injury in the multiply injured pediatric and adolescent patient is both safe and efficacious. DESIGN: Retrospective case series. SETTING: Level 1 trauma center. PATIENTS: All patients younger than 19 years old who suffered trauma to the spleen or liver between February 1978 and December 1991 (n = 103) were retrospectively identified by a trauma registry. These patients were divided into three groups: the group as a whole, those suffering multiple injuries, and those suffering either head injury or injury remote from the abdomen that required operative repair. MAIN OUTCOME MEASURES: Injury severity and outcome within each group of patients were compared based on whether the splenic or hepatic injury was managed operatively or nonoperatively. RESULTS: Mean Injury Severity Scores among the multiply injured patients were not different depending on whether the splenic or hepatic injury was managed nonoperatively or operatively. Except for a higher incidence of transfusion requirement among patients who were treated operatively, measures of morbidity among the multiply injured patients did not differ based on treatment. The success rates of nonoperative treatment among all patients, those with multiple injuries, and those with either head injury or remote injury that required surgery were 94%, 90%, and 86%, respectively. CONCLUSION: Nonoperative management of splenic and hepatic injury in multiply injured pediatric and adolescent patients, including those with head injury and injury remote from the abdomen that requires surgical intervention, is successful and is not associated with a prohibitive morbidity.

Adolescent↗

NMRPipe: a multidimensional spectral processing system based on UNIX pipes.

The NMRPipe system is a UNIX software environment of processing, graphics, and analysis tools designed to meet current routine and research-oriented multidimensional processing requirements, and to anticipate and accommodate future demands and developments. The system is based on UNIX pipes, which allow programs running simultaneously to exchange streams of data under user control. In an NMRPipe processing scheme, a stream of spectral data flows through a pipeline of processing programs, each of which performs one component of the overall scheme, such as Fourier transformation or linear prediction. Complete multidimensional processing schemes are constructed as simple UNIX shell scripts. The processing modules themselves maintain and exploit accurate records of data sizes, detection modes, and calibration information in all dimensions, so that schemes can be constructed without the need to explicitly define or anticipate data sizes or storage details of real and imaginary channels during processing. The asynchronous pipeline scheme provides other substantial advantages, including high flexibility, favorable processing speeds, choice of both all-in-memory and disk-bound processing, easy adaptation to different data formats, simpler software development and maintenance, and the ability to distribute processing tasks on multi-CPU computers and computer networks.

Magnetic Resonance Spectroscopy↗

Ergotamine-induced complex rectovaginal fistula. Report of a case.

PURPOSE: This report stresses the importance of local complications caused by ergotamine abuse for the treatment of migraine headaches. METHODS: We present an unusual case of a complex rectovaginal fistula (RVF) caused by long-term ergotamine suppository abuse. RESULTS: A 39-year-old female was referred after she had undergone a transverse colostomy for temporary fecal diversion. Evaluation, including proctoscopy, gastrograffin enema, vaginogram, and pelvic computerized tomography revealed a RVF 6 cm proximal to the dentate line with distal rectal stricture. Surgical intervention included take down of the transverse colostomy with reanastomosis, proctectomy with excision of the fistula, creation of a colonic "J-pouch" with a coloanal anastomosis, and construction of a temporary loop ileostomy. The patient had an uneventful recovery, and her ileostomy was closed three months later. Pathologic examination of the surgical specimen failed to reveal any specific etiology of the RVF. However, her ten-year use of up to five ergotamine suppositories per day for migraine treatment is associated with a local ischemic effect. Pathophysiology of this rare cause of RVF and the surgical procedure are discussed. CONCLUSION: If evidence of any side effects of ergotamine suppositories is seen, early discontinuation of the drug should be considered to avoid complications such as RVF and/or strictures.

Administration, Rectal↗

Laparoscopic removal of a large laparotomy pad forgotten in situ.

Objects forgotten during surgery are still an important complication with ethical and forensic implications. This case report describes a splenectomized patient with type II Hodgkin's disease. A large laparotomy pad (68 x 48 cm) forgotten in situ during a staging operation 6 months previously was removed laparoscopically. In asplenic patients with a permanent immune deficiency it is especially advantageous to perform surgery via the "closed" route whenever possible.

Adult↗

Laparoscopic partial splenic resection.

Twenty domestic pigs with an average weight of 30 kg were subjected to laparoscopic partial splenic resection with the aim of determining the feasibility, reliability, and safety of this procedure. Unlike the human spleen, the pig spleen is perpendicular to the body's long axis, and it is long and slender. The parenchyma was severed through the middle third, where the organ is thickest. An 18-mm trocar with a 60-mm Endopath linear cutter was used for the resection. The tissue was removed with a 33-mm trocar. The operation was successfully concluded in all animals. No capsule tears occurred as a result of applying the stapler. Optimal hemostasis was achieved on the resected edges in all animals. Although these findings cannot be extended to human surgery without reservations, we suggest that diagnostic partial resection and minor cyst resections are ideal initial indications for this minimally invasive approach.

Animals↗

Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells.

Pili and pilin antigenic variation play important roles in adhesion of Neisseria meningitidis (MC) to human epithelial and endothelial cells. We recently identified one pilin variant that confers high adhesiveness of MC to human epithelial cells in culture. However, other factor(s) also play a role in MC adhesiveness, since some nonadhesive variants of MC strain 8013 are piliated and produce the same pilin variant as adhesive derivatives. PilC1 and PilC2, high molecular weight outer membrane proteins in Neisseria gonorrhoeae, are proposed to play roles in pilus assembly. Strain 8013 also contains pilC1 and pilC2; their products function in a similar if not identical manner in pilus biogenesis. PilC1 has an additional function in that it also modulates adhesiveness of strain 8013.

Bacterial Adhesion↗