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Biomedical subjects

M S Allen

Publications and source records attributed to M S Allen.

At least 127 records · Page 7Linked to original sources

Video-assisted thoracoscopic stapled wedge excision for indeterminate pulmonary nodules.

Between June 1991 and July 1992, 118 patients (57 men and 61 women) underwent video-assisted thoracoscopy for indeterminate pulmonary nodules. Median age was 64 years (range 30 to 85 years). Thoracotomy was performed in 33 patients (28.0%) after thoracoscopy only because the nodule could not be located in 17 patients, was too large to safely resect in 5, appeared malignant in 4, and for technical reasons in 7. Eighty-five patients underwent thoracoscopic wedge excision. Twenty-one (24.7%) of these 85 patients also had thoracotomy--15 to perform formal lung resection for bronchogenic carcinoma, 3 for nondiagnostic abnormalities, 2 to locate a second nodule, and 1 for stapler malfunction. The remaining 64 patients (54.2%) had only video-assisted thoracoscopic wedge excision. A single wedge excision was performed in 56 patients, two in 6, and three in 2. Pathologic examination of these 74 nodules revealed a granuloma in 30, metastatic cancer in 25, hamartoma in 7, lymphoma in 1, and other benign lesions in 11. There were no deaths and only 4 (6.3%) complications in these 64 patients. The 64 patients treated by thoracoscopy only were compared with a similar group of 64 patients who had wedge excision via thoracotomy without prior thoracoscopy. Postoperative analgesic requirements were less in the patients treated by thoracoscopy. Median hospitalization in the thoracoscopy group was 3 days compared with 6 days in the thoracotomy group (p < 0.05). Median total charge for the thoracoscopy-only group was $12,898 as compared with $12,502 for patients undergoing wedge excision via thoracotomy. We conclude that thoracoscopic wedge excision is a safe and effective procedure in selected patients with an indeterminate pulmonary nodule. A significant number of patients (45.8%), however, required a thoracotomy to accomplish a safe operation or to ensure adequate staging and resection for malignancy. Although thoracoscopy reduces postoperative analgesia requirements and shortens hospital stay, total hospital charges were similar to charges for a wedge excision via thoracotomy.

Adult↗

Intrathoracic stomach. Presentation and results of operation.

Between January 1, 1980, and December 31, 1990, 147 patients (93 female and 54 male) were found to have an intrathoracic stomach. Median age was 69 years (range 34 to 89). Signs and symptoms occurred in 140 patients (95.2%) and were primarily obstructive. They included postprandial pain in 87 (59.2%), vomiting in 46 (31.3%), and dysphagia in 44 (29.9%); only 23 patients (15.7%) had symptoms of gastroesophageal reflux. Anemia was present in 31 patients (21.1%) and melena in 3. Elective repair was done in 119 patients and included an uncut Collis-Nissen repair in 81 patients (68.1%), a Belsey Mark IV repair in 19 (16.0%), a Nissen repair in 17 (14.3%), and a Harrington (anatomic) repair in 2 (1.7%). Thirty-two patients had complications (26.9%). There were no operative deaths. Median follow-up was 42 months. Results were excellent in 69 patients (60.0%), good in 38 (33.0%), fair in 6 (5.2%), and poor in 2 (1.7%). Five patients had emergency operations for suspected strangulation; three had gastric necrosis, and one died. Two of the four operative survivors had excellent results. Twenty-three other patients were followed up with medical management for a median of 78 months (range 12 to 268 months). In four patients progressive symptoms developed, and one patient died from aspiration. We conclude that patients with an intrathoracic upside-down stomach who have obstructive symptoms at initial presentation should undergo repair and that elective operation is safe and effective. Gastric strangulation, however, is rare.

Adult↗

Predictive binding of beta-carboline inverse agonists and antagonists via the CoMFA/GOLPE approach.

The synthesis and affinities of six new 3-substituted beta-carbolines (6-10, 12) for the benzodiazepine receptor (BzR) are described. These analogs were used both to probe the dimensions of the hydrophobic pocket in the benzodiazepine receptor and to test the predictive ability of a previously reported 3D-QSAR regression model. Of the new analogs synthesized, the gamma-branched derivatives (isobutoxy, 7, IC50 = 93 nM; isopentoxy, 9, IC50 = 104 nM) display significantly higher affinity for the BzR than either the beta-branched (sec-butoxy, 6, IC50 = 471 nM; tert-butyl ketone, 12, IC50 = 358 nM) or delta-branched (isopentoxy, 8, IC50 = 535 nM) analogs. An exception to this rule is the gamma-branched 3-benzyloxy derivative 10 (IC50 > 1000 nM) which appears to have a chain length that is too long to be accommodated by the BzR. The standard error of prediction for these six new beta-carbolines using the original regression model is significantly lower than the standard error estimate of the cross validation runs on the training set, hence the predictions made using this model are much better than expected. In order to obtain more credible predictions, a new procedure called GOLPE (generating optimal linear PLS estimates) was used to eliminate irrelevant electrostatic and steric descriptors from the regression equation. A substantial reduction in the standard error estimate resulted. The predictions from this new regression equation were somewhat less accurate than the ones obtained with the original regression equation; however the standard error of prediction and the standard error estimate are in much closer agreement. Finally, to probe the effect that the quality of the steric and electrostatic potentials has on 3D-QSAR analyses, the semiempirical MNDO parallel PRDDOE geometries and Mulliken charges used in the original analyses were replaced with ab initio 3-21G parallel 6-31G* geometries and electrostatic potential fit charges. A modest decrease in the standard error estimate and increase in cross validated R2 resulted.

Animals↗

Molecular yardsticks. Rigid probes to define the spatial dimensions of the benzodiazepine receptor binding site.

A series of rigid planar azadiindoles (8a, 8b, and 8d), benzannelated pyridodiindoles (11a, 11b, and 11d), and indolopyridoimidazoles (11c, 20, and 24) were synthesized from 4-oxo-1,2,3,4-tetrahydro-beta-carboline 5 via the Fischer indole cyclization with the appropriate arylhydrazines. These analogues were employed as probes ("molecular yardsticks") to define the spatial dimensions of the lipophilic regions of the benzodiazepine receptor (BzR) binding cleft. Benzannelated indoles 11a-d and indolopyridoimidazoles 20 and 24 were important in establishing an area of negative interaction (S1, see Figure 6, part b) in the binding cleft common to the interactions of both inverse agonists and agonists. Data from this chemical and computer-assisted analysis of the pharmacophore (see Figure 6) indicates that inverse agonists and agonists bind to the same binding region, but the pharmacophoric descriptors required for the two activities are different, in keeping with previous studies with these planar ligands. However, the hydrogen bond donating site H1 and the lipophilic region L1 in the receptor binding site are common interactions experienced by both series of ligands. The low affinities of both indolo[3,2-c]carbazole (3a) and indolo[3,2-b]isoquinoline (3b) for the BzR are consonant with the requirements of a hydrogen bond acceptor interaction at donor site H1 and a hydrogen bond donor interaction at acceptor site A2 for potent inverse agonist activity in the beta-carboline series. The hydrochloride salts of 1-aza- 8a (IC50 10.6 nM), 2-aza- 8b (IC50 51.5 nM), and 4-azadiindole 8d (IC50 11.2 nM) were found to be much more soluble in water than the corresponding salt of the parent diindole 2. Moreover, aza analogues 8a and 8b were shown to be partial inverse agonists with proconvulsant potencies comparable to that of the parent diindole 2.

Animals↗

Synthesis of novel 2-phenyl-2H-pyrazolo[4,3-c]isoquinolin-3-ols: topological comparisons with analogues of 2-phenyl-2,5-dihydropyrazolo[4,3-c]quinolin-3(3H)-ones at benzodiazepine receptors.

Based on the topology of pyrazoloquinolinones 10-12, a series of 2-phenyl-2H-pyrazolo[4,3-c]isoquinolines 6a-d, 7a-d, 8, and 9 have been synthesized and evaluated for their ability to inhibit radioligand binding to benzodiazepine receptors (BzR). Modification of the hydrogen bonding donor and acceptor characteristics of the NH and C = O functionalities of the pyrazoloquinolinones 10-12 resulted in ligands with dramatically reduced affinities (IC50 much greater than 2 microM) for BzR. The low affinities of 6a-d, 7a-d, 8, and 9 are consistent with the involvement of the NH function present on diverse classes of inverse agonists (beta-carbolines, diindoles, and pyrazoloquinolinones) with a hydrogen bond acceptor site (A2) on the binding protein. Moreover, it supports the involvement of the carbonyl function of the pyrazoloquinolinones and the pyridine nitrogen atom of beta-carbolines and diindoles with a hydrogen bond donor site (H1). Finally, the results from this work indicate that a simultaneous interaction at both hydrogen bond donor (H1) and acceptor sites (A2) at BzR is required for high affinity binding of inverse agonists.

Animals↗

Videothoracoscopic wedge excision of the lung.

Recent advances in video technology and endoscopic instrumentation have expanded the use of thoracoscopy from diagnosis to treatment of pulmonary parenchymal disease. We recently performed 14 pulmonary wedge excisions using videothoracoscopic techniques in 10 patients (7 women and 3 men). Median age was 60 years (range, 21 to 82 years). Indications were small peripheral solitary pulmonary nodules in 4 patients, diffuse pulmonary infiltrates in 4, and recurrent pneumothoraces in 2. Thoracoscopic wedge excisions were accomplished using double-lumen endotracheal anesthesia and a percutaneous stapling device. Tissue diagnosis was obtained in all patients; 6 had benign disease, 3 had metastatic cancer, and 1 had diffuse bronchoalveolar cell carcinoma. Median operating time was 90 minutes (range, 40 to 140 minutes). There were no operative deaths. The single complication was a prolonged air leak. Median hospitalization was 5 days (range, 3 to 16 days). All patients returned to full activity within 10 days of discharge. Median follow-up was 6 months (range, 5 to 8 months). We conclude that videothoracoscopic wedge excision is a safe and effective procedure for selected small peripheral indeterminate pulmonary nodules, diffuse interstitial lung diseases, and recurrent spontaneous pneumothoraces. Further evaluation and prospective studies are indicated.

Adult↗

Barrett's esophagus with high-grade dysplasia: an indication for esophagectomy?

Between 1982 and 1991, 19 patients (17 men and 2 women) with Barrett's esophagus, 10 of whom were in a surveillance program, were found to have high-grade dysplasia without evidence of invasive carcinoma. Median age was 66 years (range, 30 to 79 years). Heartburn was the most common presenting symptom. Esophagoscopy at the time of high-grade dysplasia diagnosis demonstrated normal Barrett's mucosa in 10 patients (53%), shallow ulcers in 3, slight mucosal irregularities in 2, small mucosal nodules in 2, stricture in 1, and shallow ulcer with stricture in 1. Eighteen patients underwent esophagectomy. There were no operative deaths. Nine patients (50%) had invasive carcinoma. Postsurgical stage was stage 0 in 9 patients, stage I in 6, stage IIA in 2, and stage IIB in 1. Median follow-up was 34 months (range, 2 to 116 months). Recurrent cancer developed in 2 patients. Overall 5-year survival was 66.7%; 5-year survival for patients with stage 0 disease was 100% and for stage I and II disease, 35.7%. We conclude that high-grade dysplasia in an indication for esophageal resection because of the high rate of associated early invasive carcinoma and that resection can be done safely with the expectation of excellent long-term survival. Because of these findings, we continue to recommend endoscopic surveillance in all patients with Barrett's esophagus.

Adenocarcinoma↗

Colorectal lung metastases: results of surgical excision.

Between 1960 and 1988, 139 consecutive patients underwent pulmonary resection for metastatic colorectal carcinoma. Median interval between colon resection and lung resection was 34 months. Ninety-eight patients (70.5%) had a solitary metastasis. Wedge excision was performed in 68 patients, lobectomy in 53, lobectomy plus wedge excision in 9, bilobectomy in 4, and pneumonectomy in 5. Operative mortality was 1.4%. Localized extrapulmonary colorectal cancer was also resected in 20 patients. Median follow-up was 7 years (range 1 to 20.4 years). Overall 5- and 20-year survival was 30.5% and 16.2%, respectively. Five-year survival for patients with solitary metastasis was 36.9%, as compared with 19.3% for those with two metastases (p less than 0.05) and 7.7% for those with more than two (p less than 0.01). Patients with normal carcino-embryonic antigen had a 5-year survival of 46.8% versus 16.0% for patients with increased levels (p less than 0.01). Five-year survival for patients with resected extrapulmonary disease was 30.0% versus 30.7% for those without extrapulmonary cancer (p = not significant). Repeat thoracotomy for recurrent metastases was done in 19 patients. Five-year survival after the second lung resection was 30.2%. We conclude that resection of colorectal lung metastases is safe and effective, that resectable extrapulmonary disease does not necessarily contraindicate pulmonary resection, and that repeat thoracotomy is warranted in selected patients with recurrent colorectal lung metastases.

Adult↗

Dirofilaria immitis: a rare, increasing cause of pulmonary nodules.

Dirofilariasis is an unusual but increasing cause of solitary pulmonary nodules. In this study, we reviewed the entire experience with dirofilariasis at our institution. Five such patients were identified. In all patients, the Dirofilaria immitis infection manifested as a solitary pulmonary nodule, and all patients underwent thoracotomy for diagnosis. None required systemic treatment. D. immitis is found in dog, cat, wolf, coyote, and fox populations throughout the United States, but the highest concentrations have been noted in the eastern, southeastern, and southern coastal states. The distribution of human cases of D. immitis infection has a similar pattern. Pulmonary dirofilariasis should be included in the differential diagnosis of peripheral noncalcified pulmonary nodules, especially in endemic areas.

Aged↗

Punishment of schedule-controlled behavior with beta-carboline injections: antagonism and comparisons with other compounds.

Squirrel monkeys were trained to press a key under a multiple schedule of food presentation. In the presence of either green or red stimulus lights, the 30th response produced a food pellet (fixed-ratio schedule). In the presence of the red stimulus lights (punishment component), the first response of each fixed-ratio produced either an i.v. injection of histamine [30.0-100.0 micrograms/kg/injection (inj)] or saline, accompanied by a 200-msec presentation of amber stimulus lights. Sessions in which histamine was injected alternated with sessions in which saline was injected. Another group of subjects was studied under identical schedule conditions except that electric shock was scheduled with the 200-msec stimulus light. During alternate sessions, electric shock at a high or low intensity with the stimulus, or the stimulus alone was scheduled. When performances stabilized, histamine or high intensity electric shock selectively suppressed responding in the punishment component; saline, low intensity electric shock or the stimulus light alone had no effects. Subsequently, different doses of histamine, I-nicotine, cocaine or beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) were substituted for histamine during single sessions. Histamine (17.8-100 micrograms/kg/inj), I-nicotine (32 micrograms/kg/inj) and beta-CCE (10-56 micrograms/kg/inj), but not cocaine (10.0-100.0 micrograms/kg/inj), produced a dose-related selective suppression of responding similar to that obtained with electric shock, suggesting that the drugs were functioning as punishers. Punishment by beta-CCE was antagonized with the benzodiazepine antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Bronchoalveolar carcinoma: factors affecting survival.

One hundred thirty-four consecutive patients (65 men and 69 women) underwent pulmonary resection for bronchoalveolar carcinoma. Mean age was 65 years. Lobectomy was done in 100 patients, pneumonectomy in 10, segmentectomy in 5, and wedge excision in 19. Only 10 patients had lymph node metastases (7.5%). The neoplasm was solitary in 111 patients (82.8%); 97 were in stage I, 4 were in stage II, 9 were in stage IIIa, and 1 was in stage IIIb. There were two operative deaths (1.5%). Thirty-nine complications occurred in 31 patients. Median follow-up was 5.1 years. Recurrent bronchoalveolar carcinoma developed in 45 patients. Five- and 10-year survival for patients in stage I was 75.2% and 62.0%, respectively. Survival for patients with T1 N0 M0 neoplasms was identical to expected survival and was 90.5% at 5 years, as compared with 55.4% for patients with T2 N0 M0 disease, only 35.9% for patients with multiple bilateral disease, and 0.0% for patients with bilateral disease (p less than 0.0001). Other significant factors adversely affecting survival included the presence of signs and symptoms, diffuse malignant invasion, mucin-producing tumors, and the histological absence of scar. We conclude that bronchoalveolar carcinoma has a unique natural history that is more influenced by local neoplastic processes than by lymph node metastases. Early aggressive pulmonary resection is safe and offers the potential for cure. The presence of bilateral cancer, however, is ominous.

Adenocarcinoma↗

Bronchogenic carcinoma with chest wall invasion.

Bronchogenic carcinoma with chest wall involvement continues to present a major clinical challenge. We have treated 52 patients since 1973, excluding those with superior sulcus tumors. There were 37 male and 15 female patients with an average age of 62.9 years. Chest pain was an initial symptom in 37%. All patients had negative mediastinoscopy results. Squamous cell carcinoma was present in 53% and adenocarcinoma in 35%. The median number of ribs resected was two (range, one to six), and only 2 patients required chest wall reconstruction. Pathologic staging was T3 N0 M0 in 83% and T3 N1 M0 in 17%. Operative mortality was 3.8%. Absolute 5-year survival was 26.3%. Patients who had N1 disease had a 5-year survival of only 11%. Radiation therapy was employed in 46% for positive nodes or close margins. Bronchogenic carcinoma with chest wall invasion remains potentially curable if N2 nodes are not involved. The role of radiation therapy has not been clearly defined. Morbidity and mortality should be minimal.

Adenocarcinoma↗

Carbohydrate nutrition.

An understanding of carbohydrate nutrition is essential to optimize production of dairy cattle. Two rations, both of which appear to be balanced, may have dramatically different results when fed to high-producing dairy cattle. Carbohydrates directly affect microbial protein production and therefore protein nutrition of dairy cattle. Energy intake can be maximized by considering the amount and type of carbohydrate in the ration: 1. The fiber level of the ration should be evaluated. NDF levels should be between 25 and 30% for high-producing cows in early lactation. Within this range, less fiber is required with adequate forage particle length and high frequency of grain feeding, and when buffers are fed and slowly fermented NSC sources are included in the ratio. For mid- and late-lactation cows, fiber levels are higher, ranging between 30 and 36% NDF depending upon the energy required to support milk production and restoration of body condition. 2. Provide adequate effective fiber. There should be some forage particles 1.5 in long in the ration. Limit most high-fiber byproducts to 25% of fiber requirements. 3. Feed highly digestible fiber sources. Differences in fiber digestibility of 30% will result in over 4 Mcal of NEL per day with 15 lb NDF intake. In addition, highly digestible fiber has less gut fill effect, possibly increasing dry matter intake. 4. Consider site of starch digestion. Slowly degraded starch sources such as sorghum may require steam flaking to increase ruminal fermentation. Other situations may require the addition of a slowly degraded starch source. 5. Increase frequency of concentrate feeding. Feed grain at least four times per day or include in a total mixed ration. 6. Include buffers. Under some situations (corn silage, early lactation) buffers allow more grain to be fed. 7. Add fat. Fat supplementation to milking cows has become a common practice in high-producing herds. Fat has about three times the energy of cracked corn and is often used to replace a portion of the grain to increase the energy density of the ration. It is important to realize that fat can cost up to two to three times more per megacalorie of energy than grain. Before fat is added to the ration, less expensive ways to increase energy density (listed previously) should be thoroughly explored.

Animal Nutritional Physiological Phenomena↗

Comparison of somatotropin and growth hormone-releasing factor on milk yield, serum hormones, and energy status.

Holstein cows received 12 mg/d of growth hormone-releasing factor (continuous i.v. infusion, n = 5), 14 mg/d of bST (single daily i.m. injection, n = 8), or no treatment (controls, n = 8) for 60 d. Compared with controls (31.6 kg/d), bST and growth hormone-releasing factor increased milk yield to 34.2 and 37.0 kg/d, respectively. The increase in milk yield induced by the growth hormone-releasing factor was greater than that for bST. Milk yield was not different among groups following cessation of treatment. Milk energy output was 24.2 Mcal/d in controls, and growth hormone-releasing factor increased milk energy output to 28.5 Mcal/d. Milk energy output of cows receiving bST was 26.1 Mcal/d. Growth hormone-releasing factor increased DMI (23.2 kg/d) over that of controls (21.1 kg/d), whereas bST (21.5 kg/d) did not. Relative to controls, bST increased averaged daily serum somatotropin from 1.3 to 7.6 ng/ml and insulin-like growth factor-I from 67.5 to 116.0 ng/ml. Relative to bST, growth hormone-releasing factor increased serum somatotropin to 16.3 ng/ml and insulin-like growth factor-I to 202.6 ng/ml. Relative to control (115.8 meq/dl) and bST (158.1 meq/dl), growth hormone-releasing factor increased plasma NEFA (230.3 meq/dl). During treatment, calculated energy balance was negative for cows receiving growth hormone-releasing factor but positive for bST and control cows. Milk composition, body condition score, BW, and apparent digestibility of DM were not different among treatments. We conclude that i.v. infusion of 12 mg/d mg of growth hormone-releasing factor has greater galactopoietic activity than i.m. injections of 14 mg/d of bST.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗