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Biomedical subjects

R M Shah

Publications and source records attributed to R M Shah.

At least 37 records · Page 2Linked to original sources

Pulmonary complications of cystic fibrosis in adults.

The demographics of cystic fibrosis (CF) are continuously changing, with adults representing a growing percentage of the patient population, which is expected to reach 50% by the year 2000. Pulmonary complications are primarily responsible for the high morbidity and mortality in this disease. Although the radiographic findings are quite specific, the correct diagnosis may not be suggested in the adult patient because of a lack of familiarity with its pulmonary manifestations in this age group. High-resolution CT (HRCT) has contributed to our understanding of the radiographic findings, especially at the level of the small airways. The role of imaging, including chest radiography and HRCT, is discussed. Issues that remain controversial include imaging in the acute pulmonary exacerbation, and the routine use of imaging as part of clinical scoring and in monitoring responses to new treatment modalities.

Adult↗

Effects of 5-fluorouracil on macromolecular synthesis during secondary palate development in quail.

A study was undertaken to examine the growth of normal and 5-fluorouracil-treated quail secondary palate during embryogenesis. The rates of DNA, RNA, and protein synthesis were measured in the developing quail palate by liquid scintillation counting of radiolabelled thymidine, uridine, or leucine. In addition, shelf volume was determined morphometrically. The results showed that in control palates the shelf volume increased rapidly between days 5 and 7 of incubation. Drug treatment on day 4 did not alter the shelf volume until day 9 of incubation, at which time the treated shelves were smaller than controls. In control palates, the rate of DNA synthesis decreased steadily between days 5 and 9 of incubation. A burst in RNA synthesis on day 7 of incubation was followed by an increase in protein synthesis. Administration of FU seems to exert its effect via disturbing the synthesis of RNA and protein, instead of disruption of DNA synthesis, to ultimately affect the shelf area, and thus palate morphogenesis in quail. Comparison of avian and mammalian data indicated that differences in their palate morphogenesis are also reflected in the different temporal patterns of various macromolecular synthesis.

Animals↗

Carotid exploration for acute postoperative thrombosis.

To determine the incidence of carotid reoperation and to document operative findings and clinical results, the records of patients requiring early reoperation (after less than 24 hours) during a 10-year period were analyzed with respect to operative findings, clinical outcome, and arterial patency. Endarterectomy was performed in 920 patients, with 27 strokes (3%) and 10 deaths (1%). Early re-exploration was required for 27 patients (3%) for either expanding hematoma (6 patients) or suspected thrombosis associated with a new neurologic deficit (21 patients). Two patients bled from the arteriotomy and 4 bled from surrounding tissues. Exploration for new postoperative neurologic events confirmed thrombosis in 19 cases (91%). Two patients with patent arteries and normal operative arteriograms were felt to have distal embolization, and the arteriotomy was not opened. Causes of thrombosis were intimal flap in 6 patients and closure stenosis in 11; the cause was unknown in 2 cases. All arteries were repaired over a shunt with a patch. Follow-up studies were available for 16 arteries, all of which remained patent. Of patients explored for hemorrhage, there was one death (from myocardial infarction), no neurologic events, and no late infections. Of 21 patients who underwent a second operation for neurologic deficits, 2 died, 8 were unchanged, 2 had minor residual deficit, and 9 had completely resolved deficits. Severe contralateral disease was more common among patients with residual deficits (10 of 12) compared with patients without residual deficits (0 of 9; chi-square = 8.23, P < 0.005). Carotid re-exploration is most commonly undertaken for a new neurologic deficit, usually associated with thrombosis at the operative site. Thrombosis is more often due to arterial narrowing than to an intimal defect. Prompt repair will restore patency and result in improvement in 50% of cases. Neurologic recovery is related to the status of the contralateral artery.

Acute Disease↗

Effects of 5-fluorouracil on collagen synthesis in the developing palate of hamster.

A study was undertaken to examine the effect of 5-fluorouracil (5-Fu) on collagen synthesis in the developing secondary palate. Pregnant hamsters were given 81 mg/kg 5-FU intramuscularly or 1 ml saline on day 11 of gestation. Control and treated embryonic palates, dissected from hamsters between days 11 and 13 of gestation, were incubated in a growth medium supplemented with [14C]proline. The rate of collagen synthesis, total protein and collagen isotypes were determined. The data showed that in control hamster palate the collagen synthesis peaked between days 12:00 (12 day: 0 h) and 12:04 of gestation, which is the period of shelf reorientation. In 5-FU-exposed hamster palates, the rate of collagen synthesis was lower than controls until day 12:04 of gestation followed by a rise on day 12:12 of gestation. In 5-FU-treated embryos palatal shelf reorientation took place between days 12:16 and 13:00 of gestation. Electrophoresis showed that only type I collagen was synthesized during palate development in both the control and 5-FU-treated hamster embryos. It was suggested that collagen synthesis may play a critical role in shelf reorientation in hamster since (i) new collagen was synthesized in both the control and 5-FU-treated hamster embryos prior to and during the period of normal reorientation, and (ii) in 5-FU-treated hamster embryos, a recovery in collagen synthesis precedes reorientation. Inhibition of collagen synthesis during abnormal development is only a step in the cascade of events of 5-FU-induced effects on protein synthesis.

Animals↗

Effects of vincristine on developing hamster embryos.

Using dosages and a route of administration which resembled those used clinically in humans, the effects of vincristine on developing hamster embryos were evaluated. The results showed that the drug exerted a highly toxic effect in a dose-dependent manner; however, it exhibited only a sporadic teratogenic (gross malformation) effect. The data on DNA synthesis indicated involvement of internal organs and structures, which needs to be verified. Overall, the teratogenicity of the drug was more pronounced during pre-organogenesis than during the organogenesis period. It was suggested that, in contrast to the data reported in the literature, the different biological response to vincristine in hamster may relate to the use of the dose-route combination, and is potentially relevant to developmental and transplacental carcinogenesis studies.

Abnormalities, Drug-Induced↗

Ethics in dental research. Toward developing a code of ethics.

A profession is considered to be ethical by its very nature. Hence, the ability to structure a set of principles that gives one a way to discuss the issues is crucial. However, numerous variables--such as culture, tradition of law, and stage of technological development of a Nation-State--confound issues in which principles may occasionally clash. There may not always be a right and wrong. Hence, for an international organization, a clear explanation of rules will be critical in the development of a code of ethics.

Ethics, Dental↗

A comparative study on the effects of 5-fluorouracil on glycosaminoglycan synthesis during palate development in quail and hamster.

A comparative study was undertaken to investigate the effects of 5-fluorouracil (FU) on glycosaminoglycans (GAG) synthesis during morphogenesis of the secondary palate in birds (where, unlike mammals, palate morphogenesis begins in a horizontal direction ad initium and lacks mammalian-type shelf reorientation) and mammal. Previous studies have shown that FU induces cleft palate in both birds and mammals. Air sacs of quail eggs were injected with 100 micrograms FU in 0.1 ml saline or 0.1 ml saline only. Hamsters were given intramuscular injection of 81 mg/kg FU in 1 ml saline or 1 ml saline only. Total GAG synthesis was measured by incorporation of 3H-glucosamine. Sulfated and non-sulfated GAGs were identified by Alcian Blue histochemistry combined with the use of GAG-degrading enzymes. The results indicated that a continuous synthesis of GAG at a steady rate was associated with normal palate morphogenesis in both quail and hamster. The amount of GAG synthesized in hamster palate was four-fold higher than in quail palate. In contrast to the developing hamster palate where the predominant GAG was hyaluronate, the major GAGs present during quail palate development were sulfated and were concentrated on the nasal side. FU treatment did not affect the rate of GAG synthesis in the developing palate of quail. In contrast, FU administration altered the rates of GAG synthesis, and affected hyaluronate accumulation, during palate morphogenesis in hamster.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcian Blue↗

A novel approach to the growth analysis of hamster secondary palate by histone 3 mRNA in situ hybridization.

A study was undertaken to determine the cell proliferation kinetics during the development of hamster vertical palatal shelf ad initium. Hamster embryo heads, obtained at different times between days 10 and 12 of gestation (which is the period of vertical shelf development) were processed and sectioned to localize histone 3 mRNA, a cell cycle specific gene, by in situ hybridization. Sense and antisense 35S-labelled histone 3 riboprobes were used as hybridization probes. Percent labelled cells were determined. The results showed that a high rate of random proliferation of both epithelial and mesenchymal cells was a major component of early vertical palatal growth. Subsequently, during the latter half of vertical shelf development, the proliferation rates of the epithelial and mesenchymal cells were different in a region specific manner. It was suggested that the spatio-temporal changes in the distribution of cycling mesenchymal and epithelial cells during vertical palate development may indicate their heterogeneity for subsequent segregation into appropriate phenotypes.

Animals↗

Early results with cryopreserved saphenous vein allografts for infrainguinal bypass.

PURPOSE: Cryopreserved saphenous vein allografts (CSVA) are available for use in arterial reconstructions; however, patency rates in the infrainguinal position are not well described. METHODS: We reviewed our experience with 38 patients who underwent 43 infrainguinal bypasses with CSVA as the conduit. The group includes 21 women and 17 men with a mean age of 69 +/- 11 years. Mean follow-up is 8.2 +/- 5.5 months. Logistic regression was used to analyze five variables in an attempt to identify predictors of success or failure: distal anastomosis to the popliteal artery versus a crural artery, one-vessel versus two- or three-vessel runoff, postoperative anticoagulation versus none, primary reconstructions versus reoperations, and one segment versus two segments of CSVA required. RESULTS: The cumulative patency rate at 12 months by life-table analysis is 66%. Logistic regression revealed that primary reconstructions were more likely to succeed than reoperations (p = 0.03) and operations completed with one segment of CSVA were more likely to succeed than those requiring more than one segment of vein (p = 0.03). CONCLUSIONS: We conclude that (1) the short-term patency of infrainguinal bypasses with CSVA suggests that they may be acceptable alternatives to prosthetic grafts in the below-knee position, and (2) primary reconstructions performed with one segment of CSVA are more likely to succeed.

Aged↗

Localization of peripheral pulmonary nodules for thoracoscopic excision: value of CT-guided wire placement.

OBJECTIVE: One of the indications for the rapidly expanding use of thoracoscopic surgery as an alternative to thoracotomy is the excision of peripheral lung nodules. Nodules judged too small or too far from the pleural surface to be seen or palpated during thoracoscopy must be localized beforehand. The purpose of this study was to evaluate the feasibility and effectiveness of percutaneous placement of spring hookwires to localize such nodules before video-assisted thoracoscopy. SUBJECTS AND METHODS: Under CT guidance, 17 nodules in 14 patients were preoperatively localized with the Kopans breast lesion localization system. Three patients who had solitary nodules had thoracoscopic resections for diagnosis because a previous transthoracic needle or transbronchial biopsy had been unsuccessful. Four patients who had lesions less than 8 mm in diameter had thoracoscopic biopsies because transthoracic fine-needle aspiration biopsy was not likely to be diagnostic. Seven patients, who had a total of 10 nodules, had therapeutic wedge resections of either limited metastases or a second bronchogenic carcinoma. Mean nodule diameter was 10 mm (range, 3-20 mm). The mean distance from nodule to costal pleura was 9 mm (range, 0-25 mm). At the end of the procedure, wire placement was confirmed by CT scanning. After thoracoscopy, the surgeons were questioned about the stability and utility of each hookwire localization. RESULTS: In all 17 procedures, a hookwire was placed successfully. In one case, the wire dislodged before thoracoscopy (after a 6-hr preoperative delay and severe bending of the wire during induction of anesthesia). In 16 of the 17 resections, the surgeon thought that thoracoscopic identification of the lesion would not have been possible without hookwire localization. Only one localization, across a major fissure, required placement of a second wire to localize a nodule. Wire-related complications included two instances of serious pain, five cases of clinically insignificant pneumothorax, and one large pneumothorax requiring drainage before a second nodule in the same lung was localized. CT scanning showed presumed local pulmonary hemorrhage in six cases without hemoptysis or hemothorax. CONCLUSION: CT-guided hookwire localization is easily and safely performed and permits thoracoscopic resection of lung nodules, which might otherwise be impossible.

Adult↗

Donor iliac angioplasty and crossover femorofemoral bypass.

We reviewed our experience with 99 patients who had 111 femorofemoral bypass grafts placed over a 10-year period. Mean follow-up was 36 +/- 28 months (range: 1 to 120 months). Bypass alone was performed in 89 cases (group 1). Preoperative donor iliac angioplasty was utilized in 22 cases (group 2). Overall graft failure was 21 of 89 in group 1 and 2 of 22 in group 2 (difference was not significant by chi 2: p greater than 0.05). Clinical success as calculated by life-table analysis was 95%, 83%, 75%, and 67% at 1, 3, 5, and 7 years, respectively, for group 1. Clinical success was 100% and 91% at 1 and 3 years, respectively, and 91% at 42 months for group 2. The success rates were not different for the two groups when analyzed by the log-rank test at 42 months (p greater than 0.30). We conclude that donor iliac angioplasty and femorofemoral bypass is an excellent option for patients with severe occlusive disease of one iliac artery and contralateral disease amenable to angioplasty.

Anastomosis, Surgical↗

Pathogenesis of bromodeoxyuridine-induced cleft palate in hamster.

In the present study, the morphological, histochemical, biochemical, and cellular aspects of the pathogenesis of bromodeoxyuridine (BrdU)-induced cleft palate in hamster fetuses were analyzed. Morphological observations indicated that BrdU interferes with the growth of the vertical shelves and thus induces cleft palate. At an ultrastructural level, BrdU-induced changes were first seen in the mesenchymal cells. Eighteen hours after drug administration, the initial alterations were characterized by swelling of the nuclear membrane and the appearance of lysosomes in the mesenchymal cells of the roof of the oronasal cavity. During the next 6 hr, as the palatal primordia developed, lysosomes were also seen in the overlying epithelial cells. The appearance of lysosomal activity, which was verified by acid phosphatase histochemistry, was temporally abnormal and was interpreted as a sublethal response to BrdU treatment. Later the cellular alterations subsided; 48 hr after BrdU treatment, they were absent in both the epithelial and mesenchymal cells of the vertically developing palatal shelves. Subsequently, unlike controls (in which the palatal shelves undergo reorientation and fusion), the BrdU-treated shelves remained vertical until term. Biochemical determination of DNA synthesis indicated that although there was an inhibition of DNA synthesis at the time of appearance of palatal primordia, a catch-up growth during the ensuing 12 hr may have restored the number of cells available for the formation of a vertical palatal shelf. It was suggested that BrdU affected cytodifferentiation in the palatal tissues during the critical phase of early vertical development to induce a cleft palate.

Acid Phosphatase↗

Genesis of hadacidin-induced cleft palate in hamster: morphogenesis, electron microscopy, and determination of DNA synthesis, cAMP, and enzyme acid phosphatase.

A morphological, electron microscopic, and biochemical study was undertaken to analyze the genesis of hadacidin-induced cleft palate in hamster fetuses. Gross and light microscopic observations indicated that hadacidin affected the growth of vertical palatal shelves to induce cleft palate. Electron microscopic observations showed that initial hadacidin-induced changes were seen in the mesenchymal cells. Within 12 hr of drug administration, the perinuclear space was swollen and a lysosomal response injury was evident in the mesenchymal cells. Subsequently, 24 hr after hadacidin treatment, lysosomes appeared in the epithelial cells; changes were also seen in the basal lamina which included separation of the lamina densa from the basal cells, duplication of lamina densa, and complete loss of basal lamina. Between 36 and 42 hr post-treatment, the cellular and basal lamina changes subsided, and the epithelium of vertical shelves underwent stratification. Biochemical determination of enzyme acid phosphatase indicated that the levels of enzyme activity in both the control and treated palatal tissues corresponded to the appearance of lysosomes. Measurement of cAMP levels suggested that the peak activity of cAMP corresponded to that of enzyme acid phosphatase and cell injury. The cAMP activity in hadacidin-injured cells, however, was significantly lower in comparison to that of the dying cells of control palates. Hadacidin treatment also affected DNA synthesis in the developing primordia of the palate. It was suggested that hadacidin injures the precursor cells of the palate prior to the appearance of the primordia, and subsequently affects their proliferative behavior, stunting the vertical growth of the palatal shelves and inducing a cleft palate.

Acid Phosphatase↗

Dioxin contamination and growth and development in great blue heron embryos.

A great blue heron colony located near a pulp mill in British Columbia failed to fledge young in 1987, with a concurrent sharp increase in polychlorinated dibenzo-p-dioxin (PCDD) and polychlorinated dibenzofuran (PCDF) levels in their eggs. In 1988 we tested the hypothesis that the PCDD and PCDF contamination caused reproductive failure by increasing mortality of the heron embryos in ovo. Pairs of great blue heron eggs were collected from three British Columbia colonies with low, intermediate, and high levels of dioxin contamination: Nicomekl, Vancouver, and Crofton, respectively. One egg of each pair was incubated under laboratory conditions at the University of British Columbia (UBC) while the other egg was analyzed for PCDDs and PCDFs. All incubated eggs were fertile. All eggs from the Nicomekl colony hatched, while 13 of 14 eggs from Vancouver and 12 of 13 eggs from Crofton hatched. Subcutaneous edema was observed in 4 of 12 chicks from Crofton and 2 of 13 chicks from Vancouver. No edema was seen in the chicks from Nicomekl. There was a small, but significant, negative regression of plasma calcium concentration, yolk-free body weight, tibia length, wet, dry, and ash weight, beak length, and kidney and stomach weight of the hatched chicks on the tetrachlorodibenzo-p-dioxin (TCDD) level of the paired eggs. Fewer down follicles were present on the heads of TCDD-contaminated chicks. Hence while dioxins did not cause mortality of the heron embryos in ovo, the depression of growth and the presence of edema are suggestive that dioxins at the levels found in the environment have an adverse effect on the development of great blue heron embryos.

Animals↗

Pulmonary function tests in bronchopleural fistula.

A 53-year-old white man underwent a left pneumonectomy for alveolar cell carcinoma. His postoperative course was complicated by pneumonia. At a follow-up clinic visit, the patient complained of a "roaring sound" during respiration. A follow-up PFT did not show the expected loss of volume (nitrogen washout) from a preoperative PFT, suggesting a bronchopleural fistula. A chest x-ray film and xenon lung scan confirmed the diagnosis. The fistula was surgically repaired.

Bronchial Fistula↗

Differentiation of cyclophosphamide-treated hamster secondary palate: ultrastructural and biochemical observations.

A study was undertaken to analyze the ultrastructural aspects and the enzyme acid phosphatase cytochemistry and biochemistry of the pathogenesis of cyclophosphamide (CP)-induced cleft palate in hamster fetuses. The initial CP-induced alterations were the appearance of lysosomes in the mesenchymal cells of the vertically developing palatal primordia within 8 hr of drug administration. The mesenchymal lysosomal activity, which increased during the next 16 hr, was abnormal and interpreted as a sub-lethal response to CP treatment. Subsequently, the lysosomal activity in the mesenchyme diminished gradually and, 48 hr after CP treatment, was absent. At this time, lysosomes were seen in the epithelial cells of the vertical palate. Fifty-six hours after CP treatment, unlike controls where palatal shelves were already fused, lysosomal activity subsided in the epithelial cells. Changes, however, continued to be seen at the epithelial-mesenchymal interface. These changes were characterized by discontinuity in the basal lamina, and by epithelial-mesenchymal contacts. They persisted for 8 hr but were absent thereafter. Sixty-four hours after CP administration, the vertical shelves became horizontal and remained so until term. Following analysis of data, both from the literature and from the present study, it was suggested that CP first affected mesenchymal cell proliferation, and then its cytodifferentiation, during the critical phase of early vertical development; consequently the reorientation of the shelves to a horizontal plane was delayed, inducing cleft palate.

Acid Phosphatase↗

Toward the origin of the secondary palate. A possible homologue in the embryo of fish, Onchorhynchus kisutch, with description of changes in the basement membrane area.

The oral cavity of embryos and larvae of the teleost Onchorhynchus kisutch was examined. Tissues were obtained at different ages prior to and after hatching and processed for transmission and scanning electron microscopy. A bilaterally symmetrical bulge developed from the superolateral aspect of the oral cavity and projected toward its floor, along the sides of the tongue. The bulge extended from behind the primary palate to a position midway below the eye, anterior to the gill arches, and it is suggested to be the homologue of the secondary palate of higher vertebrates. Ultrastructurally, the epithelium differentiated as the stratified squamous type and it contained mucous cells. However, the features of programmed cell death seen during palatogenesis in mammals were absent in fish. The fish palate mesenchyme, unlike that of higher vertebrates, was chondrified. Also in contrast to higher vertebrates, alterations were seen in the fish palatal basement membrane. A transient appearance of adepidermal granules in the lamina lucida region was followed by organization of collagen fibrils, first into an orthogonal pattern and then into a herring-bone arrangement, in the lamina reticularis region. There was no further advancement in the morphogenesis of fish palate. It is suggested that the differences in the morphogenesis and structure of the secondary palates of various vertebrates may reflect environmentally enforced adaptation, resulting in different programming of cells.

Animals↗

Growth of the secondary palate in the hamster following hydrocortisone treatment: shelf area, cell number, and DNA synthesis.

The contribution made by mesenchymal cells during the later stages of palatal development was examined in control and hydrocortisone-treated hamster embryos. Cross-sectional area of the palatal shelf was measured, and the numbers of both epithelial and mesenchymal cells were counted. DNA synthesis was measured by 3H-thymidine incorporation and was used as an index of growth by cell proliferation. The observations in controls indicated that, unlike development during the initial 24 hr, the later period of vertical palate development, followed by reorientation of shelves and their closure, was characterized by a steady level of mesenchymal cell number and palatal shelf area. An absence of corresponding growth in the epithelial cell number suggests that the cells may accommodate the growth either by increasing their size and/or by stretching along the basal lamina. Hydrocortisone treatment did not alter the growth pattern of cell numbers or shelf area. However, it prevented the fusion between the opposing shelves, perhaps by affecting the cytodifferentiation of the palatal tissues. Although a continuous increase in the number of mesenchymal cells during the latter half of vertical shelf development, i.e., between days 11:00 and 12:00 of gestation, is not required for reorientation and fusion of the shelves, it is not clear from the data from the present study whether a critical number of cells and/or cell density is essential for reorientation and fusion of the palate. It was suggested that, for normal palatal development, information on cell cycle and positioning of mesenchymal cells within the shelf during the vertical development may be crucial for further understanding of subsequent events of palatogenesis.

Animals↗