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Biomedical subjects

D L Miller

Publications and source records attributed to D L Miller.

At least 37 records · Page 2Linked to original sources

Embryo transfer and embryonic capsules in the bobcat (Lynx rufus).

Bobcats (Lynx rufus) (n=22) were used to test a surgical embryo transfer protocol for wild felines. Five blastocysts were collected 8-14 days post-initial copulation (PIC). Translucent capsule-like structures were recovered at 12 days PIC and are the first report of such a structure in a felid. Endometrial fibrosis was observed in one cat but, in general, post-surgical fibrosis of the uterus did not seem to impede ova or embryo transport. One embryo underwent cryopreservation and this embryo plus two other transferrable embryos were placed in recipient cats during the course of the study. No pregnancies were maintained; but one non-cryopreserved embryo was detected by ultrasound examination at 2 weeks post-transfer. This study provides valuable groundwork for future studies and warrants optimism for continued research in this area.

Animals↗

Ultrastructure of the spermatozoa from three odontocetes: a killer whale (Orcinus orca), a Pacific white-sided dolphin (Lagenorhynchus obliquidens) and a beluga (Delphinapterus leucas).

Semen was collected from three captive odontocetes: a killer whale (Orcinus orca); a Pacific white-sided dolphin (Lagenorhynchus obliquidens) and a beluga (Delphinapterus leucas). Semen was collected from the killer whale and Pacific white-sided dolphin using behavioural commands, whereas semen from the beluga was collected postmortem. Ultrastructure of the spermatozoa was examined using scanning and transmission electron microscopy. Species differences were more pronounced in the head sections followed by the midpiece and finally, the tail sections. Spermatozoa from the killer whale and beluga were similar but differed from the Pacific white-sided dolphin spermatozoa.

Animals↗

Management of respiratory symptoms associated with gastroesophageal reflux disease.

An association between gastroesophageal reflux and respiratory symptoms has been postulated to exist for some time. Several theories support a pathophysiologic relationship. Effective treatment of gastroesophageal reflux-related respiratory symptoms is not standardized. Modification of lifestyle may be beneficial, but the majority of patients should receive proton pump inhibitor therapy to suppress acid secretion. Treatment failures should be assessed for patient non-compliance, failure to make correct diagnosis, failure to recognize co-existing disease, and failure to treat adequately. If acid suppression is inadequate and acid reflux events persist even with additional acid suppression, patients should be considered for an antireflux operation with expected long-term clinical improvement and decreased medication requirements. Because laparoscopic techniques offer the benefit of antireflux surgery with reduced morbidity, this modality should be considered the current treatment of choice.

Asthma↗

Induction of lacI mutations in Big Blue Rat-2 cells treated with 1-(2-hydroxyethyl)-1-nitrosourea: a model system for the analysis of mutagenic potential of the hydroxyethyl adducts produced by 1,3-bis (2-chloroethyl)-1-nitrosourea.

We have investigated the genotoxic effects of 1-(2-hydroxyethyl)-1-nitrosourea (HENU). We have chosen this agent because of its demonstrated ability to produce N7-(2-hydroxyethyl) guanine (N7-HOEtG) and O(6)-(2-hydroxyethyl) 2'-deoxyguanosine (O(6)-HOEtdG); two of the DNA alkylation products produced by 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU). For these studies, we have used the Big Blue Rat-2 cell line that contains a lambda/lacI shuttle vector. Treatment of these cells with HENU produced a dose dependent increase in the levels of N7-HOEtG and O(6)-HOEtdG as quantified by HPLC with electrochemical detection. Treatment of Big Blue Rat-2 cells with either 0, 1 or 5mM HENU resulted in mutation frequencies of 7.2+/-2.2x10(-5), 45.2+/-2.9x10(-5) and 120.3+/-24.4x10(-5), respectively. Comparison of the mutation frequencies demonstrates that 1 and 5mM HENU treatments have increased the mutation frequency by 6- and 16-fold, respectively. This increase in mutation frequency was statistically significant (P<0.001). Sequence analysis of HENU-induced mutations have revealed primarily G:C-->A:T transitions (52%) and a significant number of A:T-->T:A transversions (16%). We propose that the observed G:C-->A:T transitions are produced by the DNA alkylation product O(6)-HOEtdG. These results suggest that the formation of O(6)-HOEtdG by BCNU treatment contributes to its observed mutagenic properties.

Animals↗

Coagulation blockade prevents sepsis-induced respiratory and renal failure in baboons.

Sepsis-induced tissue factor (TF) expression activates coagulation in the lung and leads to a procoagulant environment, which results in fibrin deposition and potentiates inflammation. We hypothesized that preventing initiation of coagulation at TF-Factor VIIa (FVIIa) complex would block fibrin deposition and control inflammation in sepsis, thereby limiting acute lung injury (ALI) and other organ damage in baboons. A model of ALI was used in which adult baboons were primed with killed Escherichia coli (1 x 10(9) CFU/kg), and bacteremic sepsis was induced 12 h later by infusion of live E. coli at 1 x 10(10) CFU/kg. Animals in the treatment group were given a competitive inhibitor of TF, site-inactivated FVIIa (FVIIai), intravenously at the time of the infusion of live bacteria and monitored physiologically for another 36 h. FVIIai dramatically protected gas exchange and lung compliance, prevented lung edema and pulmonary hypertension, and preserved renal function relative to vehicle (all p < 0.05). Treatment attenuated sepsis-induced fibrinogen depletion (p < 0.01) and decreased systemic proinflammatory cytokine responses, for example, interleukin 6 (p < 0.01). The protective effects of TF blockade in sepsis-induced ALI were confirmed by using tissue factor pathway inhibitor. The results show that TF-FVIIa complex contributes to organ injury in septic primates in part through selective stimulation of proinflammatory cytokine release and fibrin deposition.

Acute Kidney Injury↗

Familial pulmonary carcinoid tumors.

BACKGROUND: Pulmonary carcinoid tumors are rare and usually occur sporadically. Infrequently, they arise in association with multiple endocrine neoplasia type 1 (MEN1). Familial pulmonary carcinoid tumors not associated with MEN1 have not been described. METHODS: Two sets of first-degree relatives diagnosed with primary pulmonary carcinoid tumors with no clinical features of MEN1 were identified in a pair of siblings and in a mother and daughter. Mutations in the MEN1 gene were sought using polymerase chain reaction analysis on paraffin embedded tissue from two members of one of the families. RESULTS: Histopathologic and immunohistochemical studies confirmed the diagnoses of carcinoid tumors. None of these patients and no family members had features of MEN1. DNA analysis did not detect germline mutations in the MEN1 gene. CONCLUSIONS: The occurrence of familial pulmonary carcinoid tumors in the absence of MEN1 suggests a novel, rare germline mutation specific to the development of pulmonary carcinoids.

Adult↗

Significance of Clostridium tertium bacteremia in neutropenic and nonneutropenic patients: review of 32 cases.

In the nonneutropenic host, bacteremia due to Clostridium tertium is rare and of unclear significance. We describe a patient in whom presentation with Clostridium tertium bacteremia was the harbinger of Crohn's disease. In order to understand the significance of C. tertium bacteremia in neutropenic and nonneutropenic hosts, we review all 32 cases of C. tertium bacteremia that occurred at Duke University Medical Center from 1992 to 1999.

Adolescent↗

Large granular lymphocytic (LGL) leukemia in rats exposed to intermittent 60 Hz magnetic fields.

An animal model for large granular lymphocytic (LGL) leukemia in male Fischer 344 rats was utilized to determine whether magnetic field exposure can be shown to influence the progression of leukemia. We previously reported that exposure to continuous 60 Hz, 1 mT magnetic fields did not significantly alter the clinical progression of LGL leukemia in young male rats following injection of spleen cells from donor leukemic rats. Results presented here extend those studies with the following objectives: (a) to replicate the previous study of continuous 60 Hz magnetic field exposures, but using fewer LGL cells in the inoculum, and (b) to determine if intermittent 60 Hz magnetic fields can alter the clinical progression of leukemia. Rats were randomly assigned to four treatment groups (18/group) as follows: (1) 1 mT (10 G) continuous field, (2) 1 mT intermittent field (off/on at 3 min intervals), (3) ambient controls ( < 0.1 microT), and (4) positive control (5 Gy whole body irradiation from cobalt-60 four days prior to initiation of exposure). All rats were injected intraperitoneally with 2.2 x 10(6) fresh, viable LGL leukemic spleen cells at the beginning of the study. The fields were activated for 20 h per day, 7 days per week, and all exposure conditions were superimposed over the natural ambient magnetic field. The rats were weighed and palpated for splenomegaly weekly. Splenomegaly developed 9-11 weeks after transplantation of the leukemia cells. Hematological evaluations were performed at 6, 8, 10, 12, 14, and 16 weeks of exposure. Peripheral blood hemoglobin concentration, red blood cells, and packed cell volume declined, and total white blood cells and LGL cells increased dramatically in all treatment groups after onset of leukemia. Although the positive control group showed different body weight curves and developed signs of leukemia earlier than other groups, differences were not detected between exposure groups and ambient controls. Furthermore, there were no overall effects of magnetic fields on splenomegaly or survival in exposed animals. In addition, no significant and/or consistent differences were detected in hematological parameters between the magnetic field exposed and the ambient control groups.

Animals↗

Surgical treatment of hepatic and pulmonary metastases from colon cancer.

BACKGROUND: Surgical resection of isolated hepatic or pulmonary metastases secondary to colorectal cancer has been shown to yield acceptable long-term survival. However, results are inconclusive for surgical resection of both hepatic and pulmonary metastases. METHODS: We reviewed the records of all patients who underwent surgical resection of both hepatic and pulmonary metastases from colorectal cancer between 1980 and 1998. RESULTS: A total of 58 patients underwent resection of both hepatic and pulmonary metastases secondary to colorectal cancer. All patients had local control of their primary cancer before metastasectomy. There were no operative deaths. Morbidity occurred in 12% of patients. Follow-up was complete in all patients, with a median duration of 62 months (range, 6 to 201 months). The 5- and 10-year survivals were 30% and 16%, respectively. A premetastasectomy carcinoembryonic antigen level greater than 5 ng/mL increased the risk of early death (p = 0.029). Neither the number of pulmonary lesions nor the time interval between the primary surgery and the metastasectomy had a significant impact on survival (p = 0.67). At 5 years, 55% of patients were free of disease. Four patients had lymph node involvement at the time of pulmonary resection and all 4 patients died within 22 months of their pulmonary metastasectomy. CONCLUSIONS: Resection of both hepatic and pulmonary metastases secondary to colorectal cancer in highly selected patients is safe and results in long-term survival. Thoracic lymph node involvement and elevated carcinoembryonic antigen levels before pulmonary metastasectomy are associated with reduced survival.

Adult↗

Ivor Lewis esophagogastrectomy for esophageal cancer.

BACKGROUND: To examine the efficacy of the Ivor Lewis esophagogastrectomy for esophageal carcinoma prior to the widespread use of preoperative chemotherapy and irradiation, we reviewed our experience. METHODS: We reexamined the cases of 220 consecutive patients who underwent an Ivor Lewis esophagogastrectomy for esophageal cancer from January 1992 through December 1995. RESULTS: There were 196 men (89.1%) and 24 women. Median age was 65 years (range, 29 to 85 years). The results of pathological study showed adenocarcinoma in 188 patients (85.5%), squamous cell carcinoma in 31 (14.1%), and leiomyosarcoma in 1 patient (0.5%). Postsurgical staging was as follows: stage 0 in 10 patients, stage I in 19, stage IIa in 38, stage IIb in 28, stage III in 111, and stage IV in 14. The operative mortality rate was 1.4% (3 patients), and complications occurred in 83 patients (37.7%). Follow-up was 98.6% complete. Median survival for operative survivors was 1.9 years (range, 32 days to 8.7 years). The overall 5-year survival rate was 25.2%; it was 80% for patients in stage 0, 94.4% for those in stage I, 36.0% for those in stage IIa, 14.3% for patients in stage IIb, 10% for those in stage III and 0% for patients in stage IV. CONCLUSIONS: Ivor Lewis esophagogastrectomy for esophageal cancer is a safe operation. Long-term survival is stage dependent. The low survival associated with advanced cancers should stimulate the search for effective neoadjuvant therapy.

Adenocarcinoma↗

Empyema and bronchopleural fistula after pneumonectomy: factors affecting incidence.

BACKGROUND: Factors affecting the incidence of empyema and bronchopleural fistula (BPF) after pneumonectomy were analyzed. METHODS: All patients who underwent pneumonectomy at the Mayo Clinic in Rochester, Minnesota, from January 1985 to September 1998 were reviewed. There were 713 patients (514 males and 199 females). Ages ranged from 12 to 86 years (median 64 years). Indication for resection was primary malignancy in 607 patients (85.1%), metastatic disease in 32 (4.5%), and benign disease in 74 (10.4%). One hundred fifteen patients (16.1%) underwent completion pneumonectomy. Factors affecting the incidence of postoperative empyema and BPF were analyzed using univariate and multivariate analysis. RESULTS: Empyema was documented in 53 patients (7.5%; 95% confidence interval [CI], 5.7% to 9.7%) and a BPF in 32 (4.5%; 95% CI, 3.1% to 6.3%). Univariate analysis demonstrated that the development of empyema was adversely affected by benign disease (p = 0.0001), lower preoperative forced expiratory volume in 1 second (FEV1; p < 0.01) and diffusion capacity of lung to carbon monoxide (DLCO; p = 0.0001), lower preoperative serum hemoglobin (p = 0.05), right pneumonectomy (p = 0.0109), bronchial stump reinforcement (p = 0.007), completion pneumonectomy (p < 0.01), timing of chest tube removal (p = 0.01), and the amount of blood transfusions (p < 0.01). Similarly, the development of BPF was significantly associated with benign disease (p = 0.03), lower preoperative FEV1 (p = 0.03) and DLCO (p = 0.01), right pneumonectomy (p < 0.0001), bronchial stump reinforcement (p = 0.03), timing of chest tube removal (p = 0.004), increased intravenous fluid in the first 12 hours (p = 0.04), and blood transfusions (p = 0.04). Bronchial stump closure with staples had a protective effect against BPF compared with suture closure (p = 0.009). No risk factors were identified as being jointly significant in multivariate analysis. CONCLUSIONS: Multiple perioperative factors were associated with an increased incidence of empyema and BPF after pneumonectomy. Prophylactic reinforcement of the bronchial stump with viable tissue may be indicated in those patients suspected at higher risk for either empyema or BPF.

Adolescent↗

Laparoscopic repair of large paraesophageal hiatal hernia.

BACKGROUND: The objective of this study was to analyze our initial results after laparoscopic repair of large paraesophageal hiatal hernias. METHODS: Between October 1997 and May 2000, 37 patients (23 women, 14 men) underwent laparoscopic repair of a large type II (pure paraesophageal) or type III (combined sliding and paraesophageal) hiatal hernia with more than 50% of the stomach herniated into the chest. Median age was 72 years (range 52 to 92 years). Data related to patient demographics, esophageal function, operative techniques, postoperative symptomatology, and complications were analyzed. RESULTS: Laparoscopic hernia repair and Nissen fundoplication was possible in 35 of 37 patients (95.0%). Median hospitalization was 4 days (range 2 to 20 days). Intraoperative complications occurred in 6 patients (16.2%) and included pneumothorax in 3 patients, splenic injury in 2, and crural tear in 1. Early postoperative complications occurred in 5 patients (13.5%) and included esophageal leak in 2, severe bloating in 2, and a small bowel obstruction in 1. Two patients died within 30 days (5.4%), 1 from delayed splenic bleeding and 1 from adult respiratory distress syndrome secondary to a recurrent strangulated hiatal hernia. Follow-up was complete in 31 patients (94.0%) and ranged from 3 to 34 months (median 15 months). Twenty-seven patients (87.1%) were improved. Four patients (12.9%) required early postoperative dilatation. Recurrent paraesophageal hiatal hernia occurred in 4 patients (12.9%). Functional results were classified as excellent in 17 patients (54.9%), good in 9 (29.0%), fair in 1 (3.2%), and poor in 4 (12.9%). CONCLUSIONS: Laparoscopic repair of large paraesophageal hiatal hernias is a challenging operation associated with significant morbidity and mortality. More experience, longer follow-up, and further refinement of the operative technique is indicated before it can be recommended as the standard approach.

Aged↗

Lysis and sonoporation of epidermoid and phagocytic monolayer cells by diagnostic ultrasound activation of contrast agent gas bodies.

Epidermoid A431 (human carcinoma) and phagocytic RAW-264.7 cells were grown as monolayers on 5-microm thick Mylar sheets by standard culture methods. The sheets formed one window of disk-shaped ultrasound (US) exposure chambers. A diagnostic US machine in spectral Doppler mode was used for exposure with a 3.5-MHz scanhead aimed upward at the chamber in a 37 degrees C water bath. Sonoporation and cell lysis were evaluated for assessment of cell membrane damage. For both epidermoid and RAW cells on the upper window with 1% Optison contrast agent, cell lysis was detectable in addition to sonoporation. The phagocytic cells tended to retain the gas bodies when incubated with contrast agent, and membrane damage occurred even for exposure on the bottom window. The effects were also seen for RAW cells incubated with 5% contrast agent for 15 min and then rinsed before exposure. Above a threshold range for lysis and sonoporation of 0.09 to 0.23 MPa, the counts of affected cells increased for both cell lines to about 20% at 0.83 MPa. These results indicate relatively low thresholds for membrane damage induced by diagnostic US activation of contrast agent gas bodies, with a potential for targeting of these effects to phagocytic cells.

Albumins↗

Ultrastructure of the spermatozoa from a Florida manatee (Trichechus manatus latirostris).

Semen was opportunistically collected from a free-ranging, 10-year-old, 275 cm (total length) Florida manatee (Trichechus manatus latirostris) during rehabilitation treatments. Ultrastructure of the spermatozoa was examined by scanning and transmission electron microscopy and differed slightly from that described for other mammals. Comparisons to the manatee's closest phylogenetic relatives, the elephant and hyrax, were made. The manatee spermatozoa had a similar acrosome but a distinct annulus and lacked the dense bodies observed in the neck of the elephant spermatozoa. Additionally, manatee spermatozoa lacked the lateral vacuoles observed in the nuclear chromatin from of the hyrax spermatozoa. These data add to our understanding of manatees and allow for comparative studies with other species that may be useful in phylogenetic and reproductive studies.

Animals↗

Management of postpneumonectomy empyema and bronchopleural fistula.

Empyema after pneumonectomy is often associated with a bronchopleural fistula (BDF) and has a significant mortality. Management options include systemic antibiotics and observation, adequate pleural drainage, appropriate parenteral antibiotics, removal of necrotic tissue, and obliteration of residual pleural space. We prefer to treat the empyema with the procedure originally described by Clagett and Geraci in 1963. They demonstrated that postpneumonectomy empyema could be successfully treated by open pleural drainage, frequent wet-to-dry dressing changes, and when the thorax was clean, secondary chest wall closure with obliteration of the pleural cavity with an antibiotic solution. Failure was most often caused by a persistent or recurrent fistula. Because of this, when a BPF is present, the original Clagett technique was modified to include transposition of a well-vascularized muscle to cover the stump at the time of open drainage to prevent further ischemia and necrosis. Our preference is intrathoracic transposition of extrathoracic skeletal muscle. The goals of therapy for postpneumonectomy empyema remain a healthy patient with a a healed chest wall and no evidence of drainage or infection. Excellent results can be obtained in more than 80% of patients by using the Clagett procedure and intrathoracic muscle transposition when a BPF is present.

Bronchial Fistula↗

Chylothorax.

Chylothorax or chylous pleural effusion occurs when chyle accumulates in the pleural space usually secondary to disruption of thoracic lymphatics. Chyle is a milky, white, opalescent fluid that is formed when long-chain triglycerides in the diet are transformed into chylomicrons and very-low-density lipoproteins, which are then secreted into intestinal lacteals. These lymphatic channels coalesce to form the thoracic duct, which transports chyle and ultimately drains it into the left subclavian vein. Any injury to the duct (or its major tributaries) as it courses through the thoracic cavity can lead to a chylous effusion. Diagnosis depends on direct analysis of the fluid by assaying the triglyceride content and, at times, lipid electrophoretic pattern (chylomicrons). Management depends on the underlying cause and the individual clinical circumstances. Nonoperative options include observation, treatment of the underlying disease, dietary modification employing strict medium-chain triglyceride diet or total parenteral nutrition, therapeutic thoracentesis, tube thoracostomy with chemical pleurodesis, and embolization of the thoracic duct. Surgical management may include pleurectomy, talc poudrage, pleuroperitoneal shunting, and repair or ligation of the thoracic duct via thoracoscopy or thoracotomy.

Journal Article↗