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Biomedical subjects

M L Richards

Publications and source records attributed to M L Richards.

At least 19 recordsLinked to original sources

Early conversion for gangrenous cholecystitis: impact on outcome.

BACKGROUND: Early conversion from laparoscopic to open cholecystectomy for patients with gangrenous cholecystitis has been advocated. This study investigated the impact of early conversion on patient outcome. METHODS: Data from all patients with gangrenous cholecystitis undergoing laparoscopic cholecystectomy between 1992 and 2002 whose procedure had been converted to open surgery were prospectively collected and analyzed. Morbidity, length of stay, intensive care unit admission, and operative time served as outcome measures. RESULTS: Of the 97 patients in the study, 33 underwent conversion to open cholecystectomy. The conversion was early for 24% of the patients, after the initial dissection, for 33% and after an extended attempt at completion of the laparoscopic cholecystectomy for 37%. There was no difference in the overall morbidity among the groups, whereas the length of hospital stay appeared to be longer in the early conversion group. The operative time was significantly shorter after early conversion (p < 0.01, chi-square test). CONCLUSION: Laparoscopic cholecystectomy is not feasible for all patients with gangrenous cholecystitis. However, a concerted effort to perform the cholecystectomy with the minimally invasive approach does not have an adverse impact on patient outcome and is likely to benefit patients although it poses a moderate risk of conversion.

Adult↗

Open Rives-Stoppa ventral hernia repair made simple and successful but not for everyone.

BACKGROUND: The Rives-Stoppa (RS) repair of ventral incisional hernias (VIHR) is technically difficult. It involves the retromuscular placement of mesh anterior to the posterior fascia and the primary closure of the anterior fascia. Recurrence rates are 0-8%. We proposed that the operation could be done with equal success by placing the mesh in an intraperitoneal position and primarily closing the fascia anterior to the mesh. METHODS: 81 patients who had undergone an open RS-VIHR with intraperitoneal mesh were evaluated for hernia recurrence and factors associated with recurrence. RESULTS: 55 women and 26 men (mean BMI 38+/-9) underwent RS-VIHR (mean age 49+/-11 years). Of these patients, 44 (54%) had a prior VIHR, 30 (37%) had an incarcerated hernia and 34 (42%) had multiple fascial defects. PTFE was used in 83% and Prolene in 12%. Average LOS was 5.8+/-12 days. All received perioperative intravenous antibiotics and 28% were discharged on oral antibiotics. Follow-up averaged 30+/-24 months. Recurrent VIH developed in 12/81 (15%), with three occurring after removal of infected mesh and one after a laparotomy. Excluding these four, the recurrence rate was 10%. There was no correlation between hernia recurrence and age, BMI, hernia size, number of prior repairs, or LOS (t-test p>0.05). Hernia recurrence did not correlate with gender, prior peritoneal contamination, incarceration, multiple defects, adhesions, mesh type, oral antibiotics, cardiac disease, diabetes, tobacco use, or seroma (X(2) p>0.05). Those with a wound infection and/or abscess formation had a significantly higher recurrent hernia rate (60% vs. 8%, X(2) p<0.001). Patients with pulmonary disease had a significantly higher recurrence rate (50% vs. 12%, X(2) p=0.01). CONCLUSIONS: RS-VIHR with intraperitoneal mesh is a successful and less technically challenging method of repair than prior modifications. Aggressive efforts to identify infection and treat early may prevent abscess formation and subsequent recurrent hernia. Patients with chronic pulmonary disease have an unacceptably high recurrence rate and should not be considered as candidates for elective RS-VIHR.

Adult↗

Laparoscopic cholecystectomy for biliary dyskinesia: correlation of preoperative cholecystokinin cholescintigraphy results with postoperative outcome.

BACKGROUND: A gallbladder ejection fraction (EF) on cholescintigraphy of less than 35% after cholecystokinin (CCK) has been considered to be pathophysiologic and an indication for laparoscopic cholecystectomy (LC). METHODS: All patients undergoing LC for biliary dyskinesia between 1994 and 2001 were prospectively entered into a database. These patients were retrospectively evaluated with regard to demographics, the number of preoperative studies obtained, postoperative symptoms, and the number of postoperative studies obtained. RESULTS: Sixty patients underwent LC for biliary dyskinesia. The mean gallbladder EF was 14%, and 75% of patients were asymptomatic postoperatively. Persistent symptoms prompted further investigation in 6% of patients with a gallbladder EF <14% and in 35% of patients with an EF between 14 and 35% (p = 0.05). CONCLUSION: Laparoscopic cholecystectomy alleviated symptoms in 94% of patients with a gallbladder EF <14% after CCK injection. The diagnostic significance of a preoperative CCK cholescintigram (EF 14-35%) needs further investigation.

Adult↗

Role of endoscopic ultrasonography in screening and treatment of pancreatic endocrine tumours in asymptomatic patients with multiple endocrine neoplasia type 1.

BACKGROUND: Patients with multiple endocrine neoplasia (MEN) type 1 risk premature death from pancreatic endocrine tumours (PETs). Endoscopic ultrasonography (EUS) is the most sensitive imaging modality for small PETs. A screening and therapeutic approach for asymptomatic patients is delineated in which EUS plays a pivotal role. METHODS: This was a retrospective study of 15 patients with MEN-1 but with no symptoms of a PET. All patients underwent serum hormone measurement, including gastrin, and EUS. The findings were used to facilitate operative treatment. RESULTS: Six of 15 patients had a normal basal gastrin level and nine had a raised level. EUS demonstrated PETs in 14 patients and identified multiple lesions in 12. There was no predictive relationship between age or gastrin level and the number or size of PETs discovered. Thirteen patients have undergone enucleation or resection of PETs and two remain under observation. Nine of the 13 patients underwent transduodenal exploration to excise gastrinoma(s). One patient had lymph node metastases found at operation. There was no death. Self-limiting pancreatic fistula in five patients and biliary fistula in one. CONCLUSION: Early and aggressive screening using EUS identifies PETs in asymptomatic patients with MEN-1. Detection of tumours at an early stage, before the development of symptoms, lymph node metastases or liver metastases, may facilitate prompt surgical intervention and improve prognosis.

Adolescent↗

Energy cost of physical activity in cystic fibrosis.

OBJECTIVE: The purpose of this study was to compare the energy cost of standardized physical activity (ECA) between patients with cystic fibrosis (CF) and healthy control subjects. DESIGN: Cross-sectional study using patients with CF and volunteers from the community. SETTING: University laboratory. SUBJECTS: Fifteen patients (age 24.6+/-4.6 y) recruited with consent from their treating physician and 16 healthy control subjects (age 25.3+/-3.2) recruited via local advertisement. INTERVENTIONS: Patients and controls walked on a computerised treadmill at 1.5 km/h for 60 min followed by a 60 min recovery period and, on a second occasion, cycled at 0.5 kp (kilopond), 30 rpm followed by a 60 min recovery. The ECA was measured via indirect calorimetry. Resting energy expenditure (REE), nutritional status, pulmonary function and genotype were determined. RESULTS: The REE in patients was significantly greater than the REE measured in controls (P=0.03) and was not related to the severity of lung disease or genotype. There was a significant difference between groups when comparing the ECA for walking kg radical FFM (P=0.001) and cycling kg radical FFM (P=0.04). The ECA for each activity was adjusted (ECA(adj)) for the contribution of REE (ECA kJ kg radical FFM 120 min(-1)--REE kJ kg radical FFM 120 min(-1)). ECA(adj) revealed a significant difference between groups for the walking protocol (P=0.001) but no difference for the cycling protocol (P=0.45). This finding may be related to the fact that the work rate during walking was more highly regulated than during cycling. CONCLUSIONS: ECA in CF is increased and is likely to be explained by an additional energy-requiring component related to the exercise itself and not an increased REE.

Adult↗

Diabetes mellitus with hyperparathyroidism: another indication for parathyroidectomy?

BACKGROUND: Patients with hyperparathyroidism have alterations in carbohydrate metabolism characterized by insulin resistance, hyperinsulinemia, and glucose intolerance. The clinical significance of these findings in the management of patients with diabetes mellitus (DM) after parathyroidectomy for hyperparathyroidism has been controversial. METHODS: A retrospective review identified 87 patients with DM and hyperparathyroidism who underwent parathyroidectomy. The follow-up documentation of 70 patients who underwent diabetic management was then evaluated to assess the benefit of parathyroidectomy on glucose management. RESULTS: Thirteen patients had type 1 DM, and 74 patients had type 2 DM. Primary hyperparathyroidism was present in 93% of patients with type 2 DM; 64% of patients with type 1 DM had secondary hyperparathyroidism. At follow-up, glucose control was stable in 40% of patients, had improved in 37% of patients, and had deteriorated in 23% of patients (P = .003). Improved glucose control was not dependent on age, duration of DM, duration of hyperparathyroidism, length of follow-up, or calcium levels. The patients with decreased requirements had a significantly lower parathyroid hormone level (P = .05). Improved glucose control was most significant in patients whose condition was managed with oral hypoglycemics (P = .05) or insulin (P = .03). CONCLUSIONS: The clinical and laboratory investigations on the influence of hyperparathyroidism on DM support the benefit of parathyroidectomy in patients with DM. Patients with type 1 and type 2 DM show improvement in glucose control after parathyroidectomy. The presence of DM and hyperparathyroidism is an indication for parathyroidectomy because it results in either stabilization or improved glucose control in 77% of patients.

Adult↗

The rapid low-dose (1 microgram) cosyntropin test in the immediate postoperative period: results in elderly subjects after major abdominal surgery.

BACKGROUND: Recently the rapid low-dose (1 microgram) cosyntropin test has been found to be superior to the standard (250 micrograms) rapid cosyntropin test for evaluating the hypothalamic-pituitary-adrenal axis. Because the 1-microgram test has not been studied in postoperative patients, we evaluated the test after major abdominal surgery. METHODS: We performed rapid 1-microgram cosyntropin tests in 20 patients aged 65 years or older immediately and 24 hours after uncomplicated elective abdominal surgery (group A) and in 10 patients who were suspected of having adrenal insufficiency after abdominal surgery (group B). Subsequently, 250 micrograms of cosyntropin was infused over 8 hours on 2 successive days in group B patients. RESULTS: Ninety-five percent of group A patients had normal rapid 1-microgram cosyntropin test results immediately after surgery and 90% had normal test results 24 hours postoperatively. Six group B patients had abnormal rapid 1-microgram cosyntropin test results. Additional testing indicated primary adrenal insufficiency in 2 patients and central adrenal insufficiency in 1 patient; another patient probably had primary adrenal insufficiency and 2 patients appeared to be euadrenal. Four group B patients had normal rapid 1-microgram cosyntropin test results. After additional testing, 3 of these patients appeared to have normal adrenal function; 1 probably had primary adrenal insufficiency. CONCLUSION: The rapid 1-microgram cosyntropin test accurately evaluated adrenal gland function in selected patients after uncomplicated surgery. The test, however, was difficult to interpret in unselected seriously ill postoperative patients. Therefore we recommend that postoperative patients with unexplained hypotension or other features suggestive of adrenal insufficiency who have random plasma cortisol levels less than 20 micrograms/dL be treated with glucocorticoids and the hypothalamic-pituitary-adrenal axis be studied by standard tests after recovery.

Abdominal Neoplasms↗

Analysis of the promoter elements necessary for IL-4 and anti-CD40 antibody induction of murine Fc epsilon RII (CD23): comparison with the germline epsilon promoter.

IL-4 and CD40 ligand stimulate transcription of CD23 (Fc epsilonRII) in B cells and are necessary for the expression of germline epsilon mRNA and production of IgE. Because in vivo studies have shown that the Fc epsilonRII is involved in the regulation of IgE, a study was initiated to compare how IL-4 and engagement of CD40 up-regulate the Fc epsilonRII and epsilon genes. Herein, we describe the preparation of a series of linker-scanning mutants that cover the IL-4 response region in the murine Fc epsilonRII promoter, and their function when transfected into M12.4.5 and M12.4.1 B lymphoma cell lines. Several discrete elements were found to be necessary for IL-4 induction of the Fc epsilonRII gene, some of which have homology with the binding sites of known transcription factors, including NF-IL-4 and NF-kappaB. In contrast, the response element for anti-CD40 (plus IL-4) mapped to a single discrete sequence, a NF-kappaB-like site. Aligning the Fc epsilonRII and germline epsilon promoters in the region that is highly conserved between the human and mouse homologues of both genes reveals a high degree of identity, particularly within discrete clusters. Comparing the function of linker-scanning mutants of the Fc epsilonRII promoter with a similar report for germline epsilon shows that both genes require at least two homologous and similarly located DNA elements in their promoters for a full IL-4 induction. Moreover, the similar response of Fc epsilonRII and epsilon promoter-driven chloramphenicol acetyl transferase plasmids to several cytokines and other agents suggests that the two proximal promoter regions are activated by a similar cassette of factors.

Animals↗

Granulomatous appendicitis: Crohn's disease, atypical Crohn's or not Crohn's at all?

BACKGROUND: Crohn's disease isolated to the appendix has primarily been documented in case reports. We contribute a series with longterm followup and a literature review. STUDY DESIGN: A retrospective review of 1,133 consecutive appendectomy specimens over the 6-year period ending in 1994 identified seven patients with isolated granulomatous appendicitis. Two patients presented before the review period. These nine patients are reviewed and 156 patients identified in the world literature. RESULTS: Granulomatous appendicitis usually presents as an indolent course of appendicitis. No patient developed enterocutaneous fistula after appendectomy in our series. A mean followup of 7.3 years in our patients revealed no evidence of Crohn's disease. CONCLUSIONS: Granulomatous inflammatory disease isolated to the appendix differs from typical Crohn's disease with a decreased occurrence of enterocutaneous fistulas and rare recurrence. Consequently, isolated granulomatous appendicitis without small bowel or cecal involvement may not represent true Crohn's disease. Patients can be treated with minimal morbidity by appendectomy alone. If isolated granulomatous appendicitis does represent Crohn's disease, its longterm course in the majority of patients is extremely benign.

Adolescent↗

High levels of vasoactive intestinal peptide/pituitary adenylate cyclase-activating peptide receptor mRNA expression in primary and tumor lymphoid cells.

Neuropeptides exert a variety of putative immunomodulatory actions. Despite the molecular cloning of multiple forms of receptors for several neuropeptides with putative immunomodulatory effects, including vasoactive intestinal peptide (VIP), the related peptide pituitary adenylate cyclase-activating peptide (PACAP), the opiate peptides, tachykinins, somatostatin and corticotropin-releasing factor, it has not been reported that any of the receptor genes are expressed at significant levels in cells of the immune system. The low level of expression of these receptors and lack of knowledge concerning receptor subtype has impeded progress in understanding how neuropeptides regulate immune function. For example, it is not understood why VIP produces immunomodulatory effects at concentrations far below its receptor-binding affinity. Receptors for VIP and PACAP have recently been cloned. We show here by Northern blot analysis that the VIP/PACAP1 receptor mRNA is present in total RNA prepared from mouse spleen B- and T-lymphocytes. The VIP/PACAP1 receptor mRNA was also present in human peripheral blood lymphocytes, and in a B-lymphocyte and a myelocytic cell line. The mRNA for a second form of the receptor, the VIP/PACAP2 receptor, was not expressed at detectable levels in normal cells, but was detected in several human T-cell lines and a murine mast cell line. The results indicate that VIP/PACAP1 and perhaps VIP/PACAP2 receptors mediate the diverse effects of VIP and PACAP on immune cells.

Animals↗

Differential expression of VIP/PACAP receptor genes in breast, intestinal, and pancreatic cell lines.

Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP) are structurally-related neuropeptides that function as trophic factors in addition to their more classical roles as neurotransmitters. Binding and molecular cloning studies have shown that their actions are mediated by receptors encoded by at least three different genes. VIP binding has been demonstrated on many tumor types, and radiolabeled VIP has recently been used as a novel method to localize intestinal tumors in humans and their sites of metastasis. To determine the receptor subtype and level of gene expression, we screened breast, intestinal, and pancreatic, cell lines by Northern blot analysis. Breast lines expressed VIP/PACAP1 receptor mRNA levels comparable to intestinal lines, in agreement with the studies showing particularly high VIP binding in these tumors and their derived cell lines. Pancreatic cell lines expressed mRNA for several receptor types. This extends the potential utility of VIP and PACAP in the localization of tumors, and because VIP and PACAP may regulate the growth rate of some tumors by autocrine or other mechanisms, the identification of receptor subtypes on these lines sets the stage for studies in which the activity of these individual receptors in growth and other processes can be investigated.

Animals↗

Cystic neuroblastoma of infancy.

Cystic neuroblastoma is exceedingly rare; only 29 cases have been reported in the medical literature. The authors treated two children with cystic neuroblastoma. The first was a 2-week-old boy with an adrenal lesion; the second was a 15-month-old girl with solitary thoracic cystic neuroblastoma. Cystic neuroblastoma is located, almost exclusively, in the adrenal gland. In contrast to solid neuroblastoma, cystic neuroblastoma has a benign course. Cystic neuroblastoma is diagnosed earlier than solid neuroblastoma, and the former rarely presents with metastatic lesions. All previous reported cases of cystic neuroblastoma were diagnosed before 21 months of age. The presence of calcification was rare, and only 9.5% had documented elevation of the vanillylmandelic acid or homovanillic acid level. Surgical resection of all gross tumor was accomplished in 86% of children with cystic neuroblastoma, and in this group none of the patients had reported recurrent disease. Both present cases also had surgical resection of the entire gross tumor, and likewise have had no evidence of recurrent disease. This report brings the total number of reported pediatric cases of cystic neuroblastoma to 31; to the authors' knowledge, this is the first report of a child with solitary cystic neuroblastoma in an intrathoracic location.

Adrenal Gland Neoplasms↗

Regulation of the murine Fc epsilon RII (CD23) gene. Functional characterization of an IL-4 enhancer element.

The murine B cell IgE receptor (Fc epsilon RII, CD23) has been implicated in various functions including IgE regulation, Ag presentation, and B cell differentiation/activation. We have undertaken a series of studies to identify promoter sequences that are important for the constitutive and IL-4-induced expression of the murine Fc epsilon RII in M12.4.5 B lymphoma cells. By use of RNase protection analysis it was established that murine splenic B cells and M12.4.5 cells predominantly express the Fc epsilon RIIa form and that this receptor subtype accounts for the vast majority of IL-4-induced Fc epsilon RII mRNA in B cells. A 101-bp segment of the murine Fc epsilon RII proximal promoter coupled to a heterologous SV40 promoter was found to impart IL-4 inducibility in reporter assays. Removal of either 10 bp from the 5' end or 17 bp from the 3' end of this 101-bp fragment substantially reduced the IL-4 response. Both of these terminal deletions removed sequences that share homology with established IL-4 response elements of MHC class II and Ig (gamma 1 and epsilon) heavy chain genes. In addition, near the center of this 101-bp fragment lies a sequence that is highly homologous with NF-kappa B/LPS response elements previously identified upstream of the A alpha gene. DNA fragments containing this sequence together with one of the putative IL-4 response elements were able to impart a small LPS/IL-4 response in M12.4.5 cells. These results suggest that IL-4 and LPS induction of murine B cell Fc epsilon RII expression is mediated by a complex of transcription factors.

Animals↗

Complete genomic sequence of the murine low affinity Fc receptor for IgE. Demonstration of alternative transcripts and conserved sequence elements.

The complete sequence of the murine low affinity Fc receptor for IgE (Fc epsilon RII), including the 5' and 3' flanking sequences, is reported. The murine Fc epsilon RII gene spans 12.9 kb and includes 12 exons surrounding 11 introns. The composite exon sequence is virtually identical to previously reported murine Fc epsilon RII cDNA sequences. Much of the proximal promoter regions of the mouse and human homologues of Fc epsilon RII show remarkable homology to each other, including three promoter elements previously identified for MHC class II genes. The reported exon/intron structure of the human FC epsilon RII is similar to the murine homologue, except that the latter has an additional exon coding for a fourth amino acid repetitive sequence (vs three in the human gene). RNase protection studies have identified an additional transcript within intron 2 of murine Fc epsilon RIIa, similar to the human Fc epsilon RIIb form but with a different predicted sequence of the first six amino acids. This transcript is present in the mRNA of purified splenic B cells, but not in the mRNA of the Fc epsilon RII+ B lymphoma cell line M12.4.5. The murine Fc epsilon RII gene contains a large intron (4.2 kb) separating the lectin and nonlectin coding regions, and several repetitive sequences are found clustered within this intron. These results emphasize the importance of the demarcation between these domains and allude to their evolutionary and functional significance.

Amino Acid Sequence↗

mRNA variants encoding multiple forms of the high-affinity IgE receptor alpha subunit in transformed and nontransformed mast cells.

Multiple mRNA species encoding several predicted forms of the high-affinity IgE receptor alpha subunit (Fc epsilon RI-alpha) have been previously characterized from rat basophilic leukemia cells. Using the polymerase chain reaction procedure, we have extended these findings to show that one Fc epsilon RI-alpha mRNA variant, characterized by a 163-bp deletion within the coding sequence, exists in normal rat connective tissue mast cells as well as in both transformed and non transformed murine mast cell lines. In addition, a partial murine Fc epsilon RI-alpha genomic clone, spanning the internal-deletion sequence, has been identified, and from analysis of this sequence a mechanism of alternative pre-mRNA splicing is proposed. Finally, mRNA variants have been translated in a cell-free system and the protein products partially characterized.

Amino Acid Sequence↗

Biology and chemistry of low affinity IgE receptor (Fc epsilon RII/CD23).

Recent studies have established that the low affinity Fc receptor for IgE (Fc epsilon RII/CD23) is a structurally and functionally unique immunoglobulin receptor. DNA sequence analysis predicts that, in contrast to other FcR, Fc epsilon RII is not a member of the immunoglobulin gene superfamily and, indeed, is inserted into the membrane in opposite orientation from most other membrane proteins. While the Fc epsilon RII of macrophages, eosinophils, and platelets mediate IgE-dependent cytotoxicity and promote phagocytosis of IgE-antigen complexes, the function of Fc epsilon RII on B lymphocytes remains unclear. Much effort has been directed toward establishment of its role in IgE regulation, but the plurality of B cell Fc epsilon RII expression, i.e. greater than 90% of the mu + /delta + B lymphocytes, is incongruous with simply a role in regulating only IgE responses. Hence, the discovery that Fc epsilon RII is identical to the B-cell activation antigen, CD23, together with its novel structural features, suggests an additional more important role for this interesting protein and would explain the disparity between a commonly expressed receptor with apparently limited functions.

Antigens, CD↗