Evaluation of a General Practitioner with Special Interest model: lessons learned from staff experiences.

BACKGROUND: The integration of general practitioners into specialist outpatient clinics is associated with improved access to care; however, little is understood about the organisation-level factors that affect successful implementation. We aimed to identify factors that were facilitators or barriers to the implementation of a General Practitioner with Special Interest (GPwSI) model of care across a range of specialties. METHODS: Semi-structured, in-depth interviews were conducted with 25 stakeholders at 13 GPwSI clinics in operation within a Queensland public health service. A deductive content analysis was conducted using the Consolidated Framework for Implementation Research (CFIR). RESULTS: Stakeholders generally supported the GPwSI model and saw advantages to patients and specialist medical practitioners in terms of waiting lists, workload, and improving clinician self-efficacy and knowledge. A number of factors were identified as being crucial to the success of the program, such as adequate support and planning for the implementation, appropriate funding and advocacy. CONCLUSIONS: Our evaluation indicates that a GPwSI model can be a beneficial resource for improving care to patients and reducing wait lists, dependent upon adequate planning, training, and support.

Peripheral blood allogeneic microchimerism in lung and cardiac allograft recipients.

We have been investigating two parameters, donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism, to determine whether these parameters will predict a chronic rejection-free state and which recipients may be candidates for steroid withdrawal. We have identified donor antigen-specific hyporeactivity for 33% (16/48) of lung and 23% (11/47) of heart recipients. For both organ groups, the hyporeactive subgroup experienced a lower incidence of chronic rejection. The probability of donor antigen-specific hyporeactivity predicting a chronic rejection-free state is 100% for lung and 91% for heart recipients. We have identified peripheral blood allogeneic microchimerism for 77% (20/26) of lung and 36% (9/25) of heart recipients tested at 12-18 months posttransplant. Donor antigen-specific hyporeactivity correlates with a critical level of donor cells in lung recipients; the probability of high peripheral blood allogeneic microchimerism levels predicting a chronic rejection-free state in lung recipients is 100%. The results in heart recipients are not as clear with a short-, but not long-term, trend of higher chimerism levels correlating with the development of donor antigen-specific hyporeactivity. These results illustrate the usefulness of immmune parameters to predict long-term graft outcome in an organ-specific manner.

Second surgical opinion programs: dead or alive?

BACKGROUND: In the 1970s, second surgical opinion programs were established in an effort to improve medical care and to control health care costs. The cost-effectiveness of these programs has been questioned recently. STUDY DESIGN: A retrospective review was conducted of elective second-opinion surgical consultations for members of Local 32B-J of the International Service Employees Union for the years 1993-1994. Nonconfirmed consultations were reviewed against claims history data for the subsequent 2 years. Data were analyzed for rates of nonconfirmation by diagnosis and surgical specialty and for cost-effectiveness benefit. RESULTS: Of the 5,601 second surgical consultations performed, 490 procedures were not confirmed as medically necessary (9%). Claims history survey for these 490 patients for the 2 years following the consultation revealed that no operation was performed in 62%. The highest nonconfirmation rate (41%) was in plastic and reconstructive surgery, followed by gynecology (22%). The cost-benefit ratio for the program was calculated to be 1.34. CONCLUSIONS: A second surgical opinion program confers both cognitive and psychologic beneficial effects on Joint Trust Fund members and their dependents who are advised to undergo elective operations. Our current second surgical opinion nonconfirmation rate is 9%, with hysterectomy, prostatectomy, and bunionectomy among the procedures most frequently nonconfirmed. The cost-benefit ratio was estimated at 1.34.

Pretransplant exposure to donor HLA-DR antigen in random transfusion units and the development of donor antigen-specific hyporeactivity.

Our previous studies have shown that the in vitro assay of donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients (kidney, lung and heart) at low risk for immunologic complications (i.e., late acute rejection episodes and chronic rejection). Donor antigen-specific hyporeactivity is defined as a significantly decreased post- vs. pretransplant proliferative response to donor antigens while response to third-party controls remains unchanged. We analyzed whether exposure to the same HLA-DR antigen pretransplant via random blood transfusion and posttransplant via the transplanted organ influenced the development of hyporeactivity. Thirty previously nontransfused recipients, each receiving two 150 ml pretransplant random blood transfusions, were assessed for hyporeactivity at 1 year posttransplant. Of the 12 recipients with pretransplant exposure to kidney HLA-DR via transfusions, 6 (50%) developed hyporesponsiveness; in contrast, of the 18 recipients who were not preexposed, only 3 (15%) exhibited this form of immunomodulation. Of interest, 2 of the 3 hyporesponsive recipients who were not preexposed, received units containing HLA-DR antigens previously shown to share crossreactive epitopes with the kidney HLA-DR. In conclusion, these results suggest a increased incidence in the development of hyporeactivity in patients receiving pretransplant transfusions which share an HLA-DR antigen with the transplanted kidney.

Sequential measurement of peripheral blood allogeneic microchimerism levels and association with pulmonary function.

We have shown in lung recipients that high levels of peripheral blood allogeneic microchimerism at 12 to 18 months posttransplant correlated with donor antigen-specific hyporeactivity (i.e., decreased proliferative response to donor antigen in MLC while response to 3rd-party cells remains unchanged); both parameters correlated with an obliterative bronchiolitis (OB)-free state. We have expanded these studies to determine any association of sequential microchimerism levels with concomitant clinical events. In this preliminary study of 7 lung recipients, we used limiting-dilution PCR to quantify peripheral blood microchimerism at serial timepoints ranging from 3 to >48 months posttransplant. These levels were compared with a variety of immunologic and clinical parameters: acute rejection, CMV infection, OB, donor antigen-specific hyporeactivity, and pulmonary function. Pulmonary function was measured per the International Society of Heart and Lung Transplantation: "current FEV1/ baseline FEV1" (FEV1: forced expiratory volume in 1 second). Of the clinical parameters, the association between microchimerism and pulmonary function was the most striking. We observed dynamic patterns of peripheral microchimerism, which reflected the general rise and fall of FEV1. In all 7 recipients, chimerism and FEV1 were high very early posttransplant, then dropped at various rates and to various degrees. After its initial decline, microchimerism increased with FEV1 for the 1 hyporesponsive recipient; for the other 6 recipients, both values declined. These results illustrate, for the first time, that the fluctuation of peripheral blood microchimerism levels is associated with the recipient's clinical condition.

Spermatic granuloma. An uncommon complication of the tension-free hernia repair.

A patient with a sperm granuloma following a tension-free hernia repair utilizing Marlex mesh 4 years prior to presentation is described. The mechanism of granuloma formation is believed to be secondary to vas deferens injury due to erosion by the cut edges of the mesh at the medial end of the slit used to recreate the internal inguinal ring. Spermatic granuloma has been rarely described in hernia surgery and requires a previous vas deferens injury. While the more common and clinically significant events of hernia recurrence and wound infection should be considered first, the occurrence of spermatic granuloma as a cause of postoperative pain or a mass should be included in the differential diagnosis.

Allogeneic microchimerism and donor antigen-specific hyporeactivity in lung transplant recipients.

The identification of peripheral donor cells in solid organ transplant recipients has led to speculation as to the tolerogenic role of circulating donor cells. Also being debated is the possible significance of persistent donor alloantigen-presenting cells in inducing and maintaining an alloantigen-specific unresponsive state. Previously, we showed that donor antigen-specific hyporeactivity is a useful marker for identifying kidney, lung, or heart recipients at low risk for immunologic complications; we found donor antigen-specific hyporeactivity in 25% of kidney, 35% of lung, and 22% of heart recipients. All 3 hyporeactive subgroups experienced fewer late (> 3 months) rejection episodes and a lower incidence of chronic rejection. The purpose of the current study was to determine whether peripheral blood microchimerism correlates with the development of donor antigen-specific hyporeactivity and affects clinical outcome. We correlated the detection of microchimerism with in vitro proliferative response to donor antigen in 19 lung recipients who were > or = 12 months posttransplant. Allogeneic peripheral blood microchimerism was studied with a PCR-based limiting detection assay using HLA-DR sequence-specific primers. We detected microchimerism in 47% (9 of 19) of the lung recipients tested. All recipients who were donor antigen-specific hyporesponsive had microchimerism, and all recipients without detectable microchimerism were responsive to donor antigen. However, not all recipients with microchimerism developed donor antigen-specific hyporeactivity. Further, none of the hyporesponsive recipients has been diagnosed with obliterative bronchiolitis (OB). In contrast, 2 of the 4 with microchimerism who were responsive to donor antigen have been diagnosed with OB, as have 5 of the 10 who were negative for both hyporeactivity and microchimerism. Thus, long-term graft outcome may correlate more closely with donor antigen-specific hyporeactivity than with microchimerism.

Organ-specific patterns of donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in lung, kidney, and liver transplant recipients.

Although their relative importance and interaction are unclear, donor antigen(Ag)*-specific hyporeactivity and allogeneic microchimerism have been associated with improved long-term graft outcome and a lower incidence of chronic rejection in solid organ transplant recipients. We have postulated that a critical level of donor antigen, for a critical time period, is necessary to develop and maintain donor antigen-specific hyporeactivity; both the level and the time may differ by organ transplanted. In our current study, we tested donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism in liver and kidney recipients and compared these values with our previous findings in lung recipients. We tested 25 liver recipients at 12 to 29 months posttransplant: 10 (40%) had developed donor antigen-specific hyporeactivity; 5 (20%), peripheral blood allogeneic microchimerism. For all but 1 of the chimeric and hyporeactive recipients, the level of donor cells was very low (< 1:20,000). Five hyporeactive recipients and all 15 donor antigen-responsive recipients did not have detectable levels of peripheral blood microchimerism. No chronic rejection has developed in any of these recipients to date--however, a lower incidence of acute rejection was observed for those recipients with donor antigen-specific hyporeactivity (30% versus 60% without) or with peripheral blood allogeneic microchimerism (20% versus 55% without) (P = ns). These results differ from our previous findings in 19 lung recipients: at 12 to 18 months posttransplant, 35% of them had developed donor antigen-specific hyporeactivity; 47%, peripheral blood allogeneic microchimerism. All donor antigen-specific hyporeactivity recipients as well as some donor antigen-responsive recipients had peripheral blood allogeneic microchimerism. We expanded our current study to include 26 recipients and a quantitative estimate of the level of allogeneic microchimerism. We observed that the hyporesponsive recipients tended to have higher levels of donor cells in their peripheral blood (> 1:6,000) than did the responsive recipients. We previously reported that 22% of kidney recipients had developed donor antigen-specific hyporeactivity at 12 to 18 months posttransplant. In our current study of 33 kidney recipients, we observed peripheral blood allogeneic microchimerism in 7 (21%) at 12 to 18 months posttransplant. The level of donor cells was very low (approximately 1:75,000), with no correlation between donor antigen-specific hyporeactivity and peripheral blood allogeneic microchimerism at the time point tested. These studies emphasize the organ-specific nature of the development of donor antigen-specific hyporeactivity and the persistence of peripheral blood allogeneic microchimerism. Donor antigen-specific hyporeactivity correlates with very low levels of donor cells in liver recipients, while a higher critical level of donor cells is important in lung recipients. Additional sequential early posttransplant studies are necessary to further define the possible interrelationship between donor antigen and the development and maintenance of donor antigen-specific hyporeactivity.

Correlation of donor antigen-specific hyporeactivity with allogeneic microchimerism in kidney and lung recipients.

Our previous studies indicate donor antigen-specific hyporeactivity is a useful marker for identifying solid organ transplant recipients at low risk for immunological complications; the hyporeactive subgroup experiences a lower incidence of chronic rejection. One purpose of the current study was to determine whether hyporeactivity could be identified in pediatric kidney recipients and whether it correlated with improved graft outcome. Of 18 pediatric kidney recipients tested, 6 (33%) had developed donor antigen-specific hyporeactivity. All 18 experienced good graft outcome. Second, we determined whether donor antigen-specific hyporeactivity correlates with peripheral blood microchimerism and outcome in adult kidney recipients. Our previous studies of lung recipients demonstrated development of obliterative bronchiolitis in recipients with microchimerism who remain responsive, but not in recipients who had become hyporesponsive to donor antigen. Preliminary results in our current study of 23 adult kidney recipients indicate microchimerism for 6 (26%): 4 hyporesponsive and 2 responsive to donor antigen. Microchimerism was not detected for 17 recipients: 6 hyporesponsive and 11 responsive to donor antigen. One hyporesponsive/chimeric patient and 4 recipients negative for both parameters have been diagnosed with biopsy-proven chronic rejection. In summary, both hyporeactivity and chimerism are found at a higher frequency in lung than kidney recipients. Unlike lung recipients, not all hyporesponsive kidney recipients had peripheral blood chimerism. Additional numbers are needed to determine if microchimerism correlates with donor antigen-specific hyporeactivity or graft outcome.

Asymptomatic metachronous metastatic renal cell adenocarcinoma to the gallbladder. Report of a case and guidelines for evaluation of intraluminal polypoid gallbladder masses.

A case of asymptomatic metachronous metastatic unilateral renal cell adenocarcinoma to the gallbladder detected five years after resection of the primary renal neoplasm is reported here. The lesion was diagnosed by contrast enhancement of a gallbladder mass on abdominal computerized tomography scan and by color Doppler sonographic study of the gallbladder, both of which demonstrated the vascular supply to the intraluminal gallbladder mass. The biological behavior of renal cell adenocarcinoma is reviewed. Guidelines for the evaluation of intraluminal gallbladder masses are suggested.

Pneumothorax associated with laparoscopic cholecystectomy.

Pneumothorax is an uncommon but potentially serious complication that can occur during laparoscopic procedures. A patient under-going laparoscopic cholecystectomy developed an 80% pneumothorax during the course of the procedure and required chest tube insertion. She then underwent an uneventful recovery. The etiology of this complication as well as methods for avoiding this problem have been reviewed. Because of the potential serious nature of this complication, it is imperative that the surgeon be aware of the possibility and implement appropriate immediate therapy.

Metabolism of beta-muricholic acid in the hamster and prairie dog.

The metabolism of beta-muricholic acid was investigated in the prairie dog and the hamster. Intravenous infusion into bile fistula hamsters showed that beta-muricholic acid was extracted by the liver and secreted into the bile (> 85% in 1 h). Hepatic extraction of this compound and cholic acid in the prairie dog was not as rapid as in the hamster. In the bile of the prairie dog, most (93%) of the administered beta-muricholic acid was present as the taurine conjugate. In the hamster, 28% of infused beta-muricholic acid was secreted in unconjugated form, 43% as the taurine conjugate, and 22% as the glycine conjugate. In both species, the administered compound underwent little biotransformation. After intraduodenal injection of [6 alpha-3H]-labeled beta-muricholic acid into bile fistula hamsters, the bile acid was rapidly secreted into the bile; more than 80% of the administered radioactivity was recovered in 3 h. In the prairie dog, biliary recovery after intraduodenal administration of either beta-muricholic acid (43% in 3 h) or cholic acid (22% in 3 h) was slower than in the hamster. After intragastric administration, more than 80% of beta-muricholic acid was recovered unchanged in feces of both animal species.

Open cholecystectomy.

The experience with "open" biliary tract surgery is documented in this report in an effort to provide a basis for comparison with the more recent experience with laparoscopic cholecystectomy. During the years 1932 through 1984, 14,232 patients were surgically treated for nonmalignant biliary tract disease at The New York Hospital-Cornell Medical Center. Among these patients, the mortality rate was 1.7% (237 postoperative deaths). Cholecystectomy was performed in 10,749 patients, and the mortality rate was 0.6% (60 postoperative deaths). Of this group of patients, chronic cholecystitis was present in 8,910 patients, and the mortality rate was 0.4% (38 postoperative deaths). Acute cholecystitis was present in 1,839 patients, and the mortality rate was 1.2% (22 postoperative deaths). Choledochotomy as a component of the primary biliary tract operation was performed in 2,226 patients (15.6%), and there were 89 postoperative deaths (4%). In the last 6 years of this study (1978 through 1984), 1,693 patients underwent cholecystectomy alone, and the mortality rate was 0.2% (3 postoperative deaths).

Characterization of a novel gene (NKG7) on human chromosome 19 that is expressed in natural killer cells and T cells.

NKG7 is a cDNA clone generated from a human NK-cell clone. The DNA and predicted aa sequence of NKG7 is not homologous with any previously reported genes or peptides. NKG7 mRNA is expressed in activated T cells and in A-LAK cells isolated from the peripheral blood of normal individuals, and in normal human kidney, liver, lung and pancreas. Furthermore, NKG7 mRNA is expressed at high levels in TCR gamma delta-expressing CTL clones, and in some TCR alpha beta-expressing CTL clones (both CD4+ and CD8+), but is not expressed in other TCR alpha beta-expressing CTL clones and in cell lines representing B cells, monocytes, and myeloid cells. NKG7 mRNA is not expressed in normal human brain, heart, or skeletal muscle. Southern hybridization of NKG7 suggests that NKG7 is a single-copy gene localized to chromosome 19. A hydropathicity profile of the predicted 148 aa polypeptide indicates that NKG7 is a type-I integral membrane protein with a 38-aa extracellular domain and a 61-aa cytoplasmic domain. These results indicate that the NKG7 gene encodes a novel cell surface protein expressed in several cell types, including NK cells and T cells.

A multigene family on human chromosome 12 encodes natural killer-cell lectins.

We previously isolated a series of cDNA clones designated NKG2-A, B, C, and D from a human natural killer (NK) cell library. These transcripts encode a family of type II integral membrane proteins having an extracellular Ca(2+)-dependent lectin domain. The predicted peptides share structural similarities and amino acid sequence similarity with known receptor molecules. In this report, the genomic organization and mRNA expression of each of the genes were studied by using transcript-specific probes. Southern blot experiments reveal that the probes cross-hybridize with a maximum of five genes at high stringency. By probing a Southern blot prepared from a series of hamster/human hybrid somatic cell lines, we demonstrated that all of the hybridizing fragments occur on human chromosome 12. No gene rearrangement and little restriction fragment length polymorphism (RFLP) was observed with these probes. mRNA expression of the NKG2 genes occurred in NK cells and some T cells but not in other hematopoietic cell types or in other tissues tested. Each of the transcripts occurred in all three of the NK cell lines tested: however, the genes were differentially regulated in T cells. NKG2-D was expressed in nine of fourteen T-cell clones or lines in the panel, whereas NKG2-A/B was expressed in three and NKG2-C was expressed in only one. Expression of each of the transcripts was upregulated following T-cell growth factor (TCGF)-induced activation of a cloned NK cell. The limited distribution of these proteins and their sequence similarity with known receptor molecules suggest that they may function as receptors on human NK cells.