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Biomedical subjects

J Church

Publications and source records attributed to J Church.

At least 19 recordsLinked to original sources

Randomized, controlled trial of carbon dioxide insufflation during colonoscopy.

INTRODUCTION: Insufflation of air is a cause of discomfort during and after colonoscopy. Although this can be minimized by good technique, the use of carbon dioxide insufflation may provide further benefits. Carbon dioxide is rapidly absorbed and excreted through the lungs. We hypothesized that carbon dioxide would alleviate post-colonoscopy discomfort. METHODS: After they had provided informed consent, patients presenting for colonoscopy were randomized into two groups: those in whom air was used for colonoscopy and those in whom carbon dioxide was used. Pain during and ten minutes after colonoscopy was measured on a ten-point analog scale. Data are mean and 95 percent confidence limits. RESULTS: There were 124 patients in the air group and 123 in the carbon dioxide group. Age, body mass index, indication, diagnosis, and number of procedures were similar for the two groups. There were no differences between the groups in the amounts of sedation or analgesia used, the percentage of examinations that were complete (air, 98.4 percent; carbon dioxide, 95.2 percent), or patient satisfaction (on a scale of 1 to 10: air, 9.4; carbon dioxide, 9.5). Although there were more females in the carbon dioxide group (69 vs. 51), hysterectomy rates were the same. Pain scores (mean +/- 95 percent confidence interval; scale of 1 to 10) immediately after the examination were 4.3 +/- 0.3 for air and 3.6 +/- 0.3 for carbon dioxide (no significant difference). Pain scores 10 minutes later were 2.1 +/- 0.2 for air and 0.9 +/- 0.2 for carbon dioxide (P < 0.05, Student's t-test). CONCLUSION: Because there was significantly less abdominal pain ten minutes after colonoscopy in the group in whom carbon dioxide was used, carbon dioxide should be considered as an insufflating gas for colonoscopy.

Abdominal Pain↗

Predicting polyposis severity by proctoscopy: how reliable is it?

PURPOSE: Patients with familial adenomatous polyposis need prophylactic colectomy and ileorectal anastomosis or restorative proctocolectomy. Preoperative rectal polyp counts have been used as one factor to determine which operation should be done, triaging patients according to risk of rectal cancer or completion proctectomy after ileorectal anastomosis. This study was designed to examine the reliability of preoperative proctoscopy in predicting familial adenomatous polyposis severity and outcome after ileorectal anastomosis. METHODS: Familial adenomatous polyposis patients were categorized according to preoperative proctoscopy as follows: Group 1, 5 or fewer adenomas; Group 2, 6 to 19 adenomas; Group 3, 20 or more adenomas. Familial adenomatous polyposis severity was defined as mild if there were < 1,000 polyps in the colon at colectomy and severe if there were > 1,000 polyps. RESULTS: A total of 213 patients were reviewed, 80 in Group 1, 59 in Group 2, and 74 in Group 3. There was no difference among the groups in mean age at presentation. Patients with fewer than five rectal adenomas were predominately females. They rarely had symptoms (22.8 percent), had mostly mild polyposis (86.5 percent), and in 74 of 80 cases underwent ileorectal anastomosis. Only six underwent restorative proctocolectomy. Of those having an ileorectal anastomosis, five needed later proctectomy, none for cancer. Patients with 6 to 19 rectal polyps were a similar group to those with 5 or fewer. Most were asymptomatic (67.8 percent), most had mild polyposis (81.6 percent), and 54 of 59 underwent ileorectal anastomosis (5 had restorative proctocolectomy). Only 3 of the 54 having ileorectal anastomosis needed subsequent proctectomy, 2 for rectal cancer. The patients with 20 or more rectal polyps were different. They usually presented with symptoms (86 percent), the majority (56.6 percent) had severe polyposis, and only 50 percent (37/74) underwent ileorectal anastomosis, the other half having restorative proctocolectomy. Of the 37 patients with an ileorectal anastomosis, 13 needed later proctectomy (35.1 percent), 4 for cancer (10.8 percent). CONCLUSION: Fewer than five rectal adenomas at presentation almost always predicts mild disease, and patients do well after ileorectal anastomosis. Twenty or more adenomas usually means severe disease. Patients with 6 to 19 adenomas are often mildly affected, but their phenotype is less benign than that of patients with fewer than five polyps. Although not foolproof, proctoscopy is a useful test in triaging patients with familial adenomatous polyposis according to disease severity.

Adenomatous Polyposis Coli↗

The clinical application of a urine albumin:creatinine ratio point-of-care device.

INTRODUCTION: Microalbuminuria is an accepted predictive marker for the early detection of renal disease and the identification of patients at high risk of developing complications of diabetes and hypertension. The Bayer Clinitek 50 is a urine chemistry point-of-care analyser for the semi-quantitative measurement of albumin and creatinine and calculation of albumin:creatinine ratio (ACR). METHOD: Urine samples were obtained from 252 consecutive patients attending a city center diabetic clinic, and from 40 patients on admission to the ICU. Albumin and creatinine measurements were carried out using the Clinitek 50 and by the central laboratory. RESULTS: The Clinitek 50 results agreed with the central laboratory results in 89% of the diabetic patient samples and 80% of the ICU patient samples. Excluding samples defined as normal by the Clinitek 50 (ACR<3.4 mg/mmol) would have resulted in an 80% reduction in samples sent to the lab for further quantification. The average length of stay in the group of ICU patients with normal ACR was significantly less than for those patients with an abnormal ACR (p<0.005). CONCLUSIONS: The Clinitek 50 provides useful, immediate clinical information regarding the microalbuminuria status for use in the diabetic clinic setting or as a potential immediate risk management tool in intensive care.

Albuminuria↗

Safety and longterm efficacy of strictureplasty in 314 patients with obstructing small bowel Crohn's disease.

BACKGROUND: Since its introduction in the early 1980s, strictureplasty (SXP) has become a viable option in the surgical management of obstructing small bowel Crohn's disease. Questions still remain regarding its safety and longterm durability in comparison to resection. Precise indications and contraindications to the procedure are also not well defined. STUDY DESIGN: A retrospective review of all patients undergoing SXP for obstructing small bowel Crohn's disease at the Cleveland Clinic between 1984 and 1999 was conducted. A total of 314 patients underwent a laparotomy that included the index SXP The total number of SXPs performed was 1,124, with a median of two (range 1 to 19) per patient. Sixty-six percent of patients underwent a synchronous bowel resection. Recurrence was defined as the need for reoperation. Followup information was determined by personal interviews, phone interviews, or both. RESULTS: The overall morbidity rate was 18%, with septic complications occurring in 5% of patients. Preoperative weight loss (p = 0.004) and older age (p = 0.008) were found to be significant predictors of morbidity. The surgical recurrence rate was 34%, with a median followup period of 7.5 years (range 1 to 16 years). Age was found to be a significant predictor of recurrence (p = 0.02), with younger patients having a shorter time to reoperation. CONCLUSIONS: This large series of patients with longterm followup confirms the safety and efficacy of strictureplasty in patients with obstructing small bowel Crohn's disease. The 18% morbidity and 34% operative recurrence rates compare favorably with reported results of resective surgery. Caution should be used in patients with preoperative weight loss, because they experienced higher complication rates. Although young patients seem to follow an accelerated course, SXP remains indicated as part of an overall strategy to conserve intestinal length.

Adolescent↗

Repair of recurrent rectovaginal fistulas.

BACKGROUND: Recurrent rectovaginal fistulas (RRVFs) pose a challenging problem, which can be treated by different surgical procedures. We performed this study to determine the ultimate success rate of various repair techniques. METHODS: Using a standard data collection form, we retrospectively reviewed charts of patients treated for RRVF. RESULTS: Between 1991 and 2000, 57 procedures were performed in 35 women who presented with RRVF. Median follow-up was 4 months (interquartile range, 1,25). The causes of RRVF included obstetrical injury (n = 15), Crohn's disease (n = 12), fistula occurring after proctocolectomy with ileal pouch-anal anastomosis (for ulcerative colitis, n = 3; indeterminate colitis, n = 1; familial polyposis, n = 1), cryptoglandular disease (n = 2), and fistula occurring immediately after low anterior resection for rectal cancer (n = 1). The methods of repair used included mucosal advancement flap (n = 30), fistulotomy with overlapping sphincter repair (n = 14), rectal sleeve advancement (n = 3), fibrin glue (n = 1), proctectomy with colonic pull-through (n = 2), and ileal pouch revision (n = 6). Twenty-seven of 34 (79%) patients with adequate follow-up eventually healed after a median of 2 operations. Logistic regression was used to analyze outcome according to etiology of fistula, patient age, number of prior repairs, time interval between last repair and current repair, and presence of fecal diversion. Crohn's disease, the presence of a diverting stoma, and decreased time interval since prior repair were associated with a poorer outcome. CONCLUSIONS: Most RRVFs can be successfully repaired, although repeated operations may be necessary. Delaying repair may improve outcome.

Adult↗

In situ calibration and [H+] sensitivity of the fluorescent Na+ indicator SBFI.

Despite the popularity of Na+-binding benzofuran isophthalate (SBFI) to measure intracellular free Na+ concentrations ([Na+](i)), the in situ calibration techniques described to date do not favor the straightforward determination of all of the constants required by the standard equation (Grynkiewicz G, Poenie M, and Tsien RY. J Biol Chem 260: 3440-3450, 1985) to convert the ratiometric signal into [Na+]. We describe a simple method in which SBFI ratio values obtained during a "full" in situ calibration are fit by a three-parameter hyperbolic equation; the apparent dissociation constant (K(d)) of SBFI for Na+ can then be resolved by means of a three-parameter hyperbolic decay equation. We also developed and tested a "one-point" technique for calibrating SBFI ratios in which the ratio value obtained in a neuron at the end of an experiment during exposure to gramicidin D and 10 mM Na+ is used as a normalization factor for ratios obtained during the experiment; each normalized ratio is converted to [Na+](i) using a modification of the standard equation and parameters obtained from a full calibration. Finally, we extended the characterization of the pH dependence of SBFI in situ. Although the K(d) of SBFI for Na+ was relatively insensitive to changes in pH in the range 6.8-7.8, acidification resulted in an apparent decrease, and alkalinization in an apparent increase, in [Na+](i) values. The magnitudes of the apparent changes in [Na+](i) varied with absolute [Na+](i), and a method was developed for correcting [Na+](i) values measured with SBFI for changes in intracellular pH.

Animals↗

Community hospitals for the new millennium.

There is a lack of basic information regarding the numbers of and facilities offered by community hospitals. This survey identified 471 community hospitals in the United Kingdom containing 18,579 beds with 20% of general practitioners having admitting rights. The majority of hospitals provide a comprehensive range of rehabilitation services and consultant outpatient clinics. Community hospitals are potentially an important resource in providing intermediate care in the community.

Health Services Accessibility↗

Recombinant CD4-IgG2 in human immunodeficiency virus type 1-infected children: phase 1/2 study. The Pediatric AIDS Clinical Trials Group Protocol 351 Study Team.

The use of recombinant CD4-IgG2 in pediatric human immunodeficiency virus type 1 (HIV-1) infection was evaluated by single and multidose intravenous infusions in 18 children in a phase 1/2 study. The study drug was well tolerated, and dose proportionality was observed in terms of area under time-concentration curve and peak serum concentration. Acute decreases of >0.7 log(10) copies/mL in serum HIV-1 RNA concentration were seen in 4 of the 6 children treated with 4 weekly 10 mg/kg doses. At 14 days after treatment, 3 children had sustained reductions in serum HIV-1 RNA; the other children had rebounded to baseline levels or above. By 28 days after therapy, the peak HIV-1 cellular infectious units was reduced in all 6 children, including the 2 who had experienced an earlier transient increase in values. Thus, recombinant CD4-IgG2 treatment of HIV-1-infected children appears to be well tolerated and capable of reducing HIV-1 burden.

Adolescent↗

Family history of colorectal cancer: how often and how accurately is it recorded?

PURPOSE: A family history of colorectal cancer is an important risk factor for the disease. A positive family history means that endoscopic screening should be recommended and a strongly positive family history raises the possibility of a dominantly inherited syndrome. This study was performed to find how often and how accurately a family history of colorectal cancer was recorded in the charts of patients on a colorectal surgical ward. A second aim was to see whether family history-taking could be improved. METHODS: The charts of 100 inpatients on a colorectal surgical floor were reviewed for the presence of a family history of colorectal cancer. Any chart documentation was compared with a family history obtained by a detailed interview. The chart review was repeated four years later. RESULTS: In the initial review, we found that a family history was recorded in 45 of 100 charts. It was accurate for colorectal cancer in 36 charts. Four years later, the rate of family history recording increased to 61 of 96, whereas the accuracy rate (45/61) did not change. Responses to a simple screening question asking about a family history of colorectal cancer were accurate in 77 percent of patients. CONCLUSIONS: Not all colorectal surgical patients have their family histories recorded, and even when it is recorded, it is not always correct. Despite improvement during a four-year period, there is still room for further improvement in the recording of a family history of colorectal cancer. Physicians should make an effort to ask this question and document the response in the hospital chart.

Adult↗

Intussusception of the vermiform appendix: preoperative colonoscopic diagnosis of two cases and review of the literature.

Intussusception of the appendix is an uncommon condition, and the diagnosis is rarely made preoperatively. Making an accurate diagnosis before laparotomy is important in providing the optimal treatment for the patient. We present the clinical and endoscopic features of two cases of intussusception of the appendix and review the literature. Diagnosis was made preoperatively by colonoscopy in these cases and an elective appendectomy was performed. Appendiceal intussusception should be considered in the differential diagnosis of abdominal pain. Colonoscopy can be a valuable tool in establishing this diagnosis and in selecting the appropriate management.

Abdominal Pain↗

Gene therapy for pediatric AIDS.

Gene therapy is an experimental treatment modality under investigation for applications to HIV-1 infection. We have developed retroviral vectors carrying anti-HIV-1 genes, demonstrated that these genes cause significant suppression of HIV-1 replication in cultures of primary hematopoietic cells, and performed a clinical trial in pediatric AIDS patients. Four HIV-1-infected children and adolescents underwent bone marrow harvest from which CD34+ cells were isolated and transduced by a retroviral vector carrying an RRE decoy gene. The cells were re-infused into the subjects, without complications, showing that gene transfer in pediatric AIDS patients in safe and feasible. However, gene-containing leukocytes in the peripheral blood were seen only at a low level and only in the first months following cell infusion. To attain some degree of efficacy, it will be necessary to achieve a higher level of gene transfer and to obtain sustained gene expression. We are currently developing new gene transfer methods and vectors designed to improve the results in future trials. If it becomes possible to reach the ideal goal of producing high percentages of T lymphocytes and monocytic cells that are resistant to HIV-1 infection, gene therapy could serve as a complement to antiretroviral drug therapy and help to sustain immunologic function.

Acquired Immunodeficiency Syndrome↗

Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis.

Exisulind (sulindac sulfone; FGN-1), a metabolite of sulindac without known effects on prostaglandin synthesis, can promote apoptosis and inhibit tumorigenesis in preclinical systems. We performed a Phase I trial of this compound in patients with familial adenomatous polyposis (FAP) to examine the tolerability and safety of this drug in the cancer chemoprevention setting. Six patients each were treated with exisulind at doses of 200, 300, and 400 mg p.o. twice a day. Reversible hepatic dysfunction was noted in four of six patients treated at the 400-mg p.o., twice-a-day dose level, but in only one to two of six patients treated at each of the lower dose levels. The serum half-life of exisulind was 6-9 h; little drug accumulation was noted over time. A nonsignificant trend toward increased apoptosis in polyps was noted at the maximum tolerated dose, but no decrease in polyp numbers or significant effects on cellular proliferation was noted. After treatment, polyps tended to display a "halo" appearance grossly and mucinous differentiation histologically. The maximum safe dose of exisulind is 300 mg p.o. twice a day in patients with subtotal colectomies. Reversible hepatic dysfunction limits further dose escalation. A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted.

Adenomatous Polyposis Coli↗

A clinical trial of retroviral-mediated transfer of a rev-responsive element decoy gene into CD34(+) cells from the bone marrow of human immunodeficiency virus-1-infected children.

Genetic modification of hematopoietic stem cells with genes that inhibit replication of human immunodeficiency virus-1 (HIV-1) could lead to development of T lymphocytes and monocytic cells resistant to HIV-1 infection after transplantation. We performed a clinical trial to evaluate the safety and feasibility of this procedure, using bone marrow from four HIV-1-infected pediatric subjects (ages 8 to 17 years). We obtained bone marrow, isolated CD34(+) cells, performed in vitro transduction with a retroviral vector carrying a rev-responsive element (RRE) decoy gene, and reinfused the cells into these subjects with no evidence of adverse effects. The levels of gene-containing leukocytes in peripheral blood samples in the 1 year after gene transfer/cell infusion have been extremely low. These observations support the potential of performing gene therapy for HIV-1 using hematopoietic cells, but emphasize the need for improved gene transfer techniques.

Acquired Immunodeficiency Syndrome↗

The rise and fall of the Aldabran giant tortoise population.

At the end of the 19th century, after prolonged and extensive harvesting, indigenous giant tortoises had been eliminated from all islands in the Indian Ocean, except Aldabra atoll, where only a few survived. With greatly reduced levels of exploitation during the 20th century, the population recovered to a revised estimated total of 129,000 in 1973-1974, when the first sample census was conducted. A repeat census in 1997 revealed a highly significant reduction in numbers over the past 24 years to an estimated total of 100,000. The great majority of tortoises are still found at relatively high density in south-eastern Grande Terre, where the number of animals has declined by more than one-third. In contrast, low-density subpopulations on Malabar and Picard have almost doubled in size, but they represent less than 5% of the total population. Corroborative evidence for the crash in the Grande Terre subpopulation comes from two independent observations: a significant increase in tortoise mortality; and a significant decline in tortoise counts on long-term population monitoring transects. These population changes are attributed to natural population regulatory mechanisms, exacerbated by low rainfall years in the period 1980-1997, including two consecutive years of below average rainfall in 1995-1996 and 1996-1997.

Animals↗