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Biomedical subjects

S C Marks

Publications and source records attributed to S C Marks.

At least 55 records · Page 3Linked to original sources
PubMed1998

Effects of zinc and nutritional status on clinical outcomes in head and neck cancer.

The head and neck cancer patient often presents with both protein malnutrition and trace element deficiencies. Zinc has been found to be deficient in many head and neck cancer patients. In this study, pretreatment zinc status and nutritional status (measured by the Prognostic Nutritional Index [PNI]) were correlated with clinical outcomes in 47 patients. The patients were followed-up for a median of 52 mo from the time of enrollment. Our results showed that the tumor size and overall stage correlated significantly to zinc status whereas no such correlation was seen with PNI, alcohol intake, or smoking in our subjects. The results also showed that impaired zinc status was associated with an increased number of treatment morbidities, unplanned hospitalizations, and treatment delays (P < 0.05). Nutritional status was not associated with any studied outcome variable. The disease-free interval was highest for the group which had both zinc-sufficient and nutrition-sufficient status. Although our data do not prove conclusively, they do suggest that impaired zinc status at presentation may contribute to treatment morbidity, and that for an optimal mean disease-free interval, a sufficient zinc and nutritional status is required.

Aged↗
PubMed1998

Nutritional and zinc status of head and neck cancer patients: an interpretive review.

In this review, we provide evidence based on our studies, for zinc deficiency and cell mediated immune disorders, and the effects of protein and zinc status on clinical morbidities in patients with head and neck cancer. We investigated subjects with newly diagnosed squamous cell carcinoma of the oral cavity, oropharynx, larynx, and hypopharynx. Patients with metastatic disease and with severe co-morbidity were excluded. Nutritional assessment included dietary history, body composition, and prognostic nutritional index (PNI) determination. Zinc status was determined by zinc assay in plasma, lymphocytes, and granulocytes. Pretreatment zinc status and nutritional status were correlated with clinical outcomes in 47 patients. Assessment of immune functions included production of TH1 and TH2 cytokines, T cell subpopulations and cutaneous delayed hypersensitivity reaction to common antigens. At baseline approximately 50% of our subjects were zinc-deficient based on cellular zinc criteria and had decreased production of TH1 cytokines but not TH2 cytokines, decreased NK cell lytic activity and decreased proportion of CD4+ CD45RA+ cells in the peripheral blood. The tumor size and overall stage of the disease correlated with baseline zinc status but not with PNI, alcohol intake, or smoking. Zinc deficiency was associated with increased unplanned hospitalizations. The disease-free interval was highest for the group which had both zinc sufficient and nutrition sufficient status. Zinc deficiency and cell mediated immune dysfunctions were frequently present in patients with head and neck cancer when seen initially. Zinc deficiency resulted in an imbalance of TH1 and TH2 functions. Zinc deficiency was associated with increased tumor size, overall stage of the cancer and increased unplanned hospitalizations. These observations have broad implications in the management of patients with head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1998

Acute sinusitis in the rabbit model: histologic analysis.

OBJECTIVES: Characterize the histology of the rhinogenic model of sinusitis and compare this with existing models of sinusitis. STUDY DESIGN: Prospective controlled trial in animals. METHODS: New Zealand white rabbits were implanted with a synthetic sponge, which was then impregnated with Streptococcus pneumoniae bacteria. After a specified time the animals were sacrificed, and whole-mount sectioning of both the infected and noninfected sinuses was performed. The sinuses were carefully examined for evidence of inflammatory changes. RESULTS: This model produced a sinus infection that is characterized by luminal exudates of neutrophils and eosinophils, mucosal infiltration with lymphocytes and plasma cells, and epithelial degeneration. In addition, discrete lymphoid follicles were identified in both the implanted and nonimplanted sides that in the implanted sides appear to hypertrophy and liberate leukocytes into the sinus lumen. Other areas were observed where luminal exudates seem to act on and degrade mucosa that has little or no underlying inflammation. In severely infected sinuses submucosal vacuole formation with overlying granulation tissue was observed. CONCLUSIONS: The rhinogenic model of sinusitis demonstrates features typical of other known models of sinusitis. In addition, there appear to be unique features of this model, specifically the identification of discrete lymphoid aggregates, which suggest that this model has the potential to be valuable for the study of the immune response of the sinuses.

Acute Disease↗
PubMed1998

Effect of CSF-1 on in vivo expression of c-fos in the dental follicle during tooth eruption.

It has been demonstrated that both colony-stimulating factor-one (CSF-1) and the transcription factor, c-fos are required for tooth eruption. Osteopetrotic mutant rats deficient in CSF-1 activity have unerupted teeth which can be induced to erupt by injections of CSF-1, and osteopetrotic mice deficient in c-fos, have unerupted teeth. Both CSF-1 and c-fos are expressed and translated in the dental follicle, the tissue that is required for eruption. Recent in vitro studies indicate that CSF-1 can enhance the expression of the c-fos gene in cultured dental follicle cells, but the effects in vivo are not known. In the present studies. postnatal rats were injected with 10(6) units of CSF-1 at different ages from birth to day 10 and sacrificed 30 min after injection. Isolation of total RNA from the follicle and reverse transcription PCR showed that CSF-1 injection enhanced the expression of c-fos over the non-injected controls. Chronologically, day 3 postnatally appeared to show the greatest increase of c-fos mRNA following CSF-1 injection. These results suggest that one of the functions of CSF-1 in tooth eruption is to enhance the early expression of c-fos. In turn, c-fos might act to promote fusion of monocytes into the osteoclasts needed for alveolar bone resorption and tooth eruption.

Animals↗
PubMed1998

Actin mRNA isoforms are differentially sorted in normal osteoblasts and sorting is altered in osteoblasts from a skeletal mutation in the rat.

Actin isoform sorting has been shown to occur in a variety of cell types in culture. To this list we add osteoblasts, in which we show by in situ hybridization that beta-actin is distributed primarily in cell processes and on one side of the nucleus and gamma-actin has a perinuclear distribution. Osteoblasts from the skeletal mutation toothless (tl), evaluated under identical conditions, fail to sort these actin isoforms differentially and exhibit diffuse labeling as their major manifestation. Northern analyses of actin mRNAs showed no differences between normal and mutant cultures. Shortened osteoblast life span and an inability to direct osteoclast-mediated bone resorption have recently been demonstrated in tl mutants. The present results suggest that a failure of osteoblasts to sort actin mRNAs may be related to one or both of these pathological manifestations in this mutation and represent, to our knowledge, the first correlation of an actin mRNA-sorting abnormality with a mammalian disease.

Actins↗
PubMed1998

A regional approach to the classic metaphyseal lesion in abused infants: the distal femur.

OBJECTIVE: The purpose of this study was to analyze the spectrum of morphologic alterations of the classic metaphyseal lesion involving the distal femur of abused infants and to identify features that aid in radiologic diagnosis and assessment of healing. MATERIALS AND METHODS: Thirty-one infants who died with evidence of inflicted skeletal injury were studied with high-detail skeletal surveys, resected specimen radiography, and histologic analysis. We recorded the number of fractures, the portions of the distal femoral metaphyses involved, and the age of the lesions. RESULTS: Fifteen classic metaphyseal lesions of the distal femur were seen in 11 infants. The lesions were bilateral in four infants and unilateral in seven. Nine healing and three acute classic metaphyseal lesions were found. In the remaining three lesions, the age of the lesions was indeterminate. Fractures always involved the posteromedial aspect of the femur; anterior and lateral extension occurred in more diffuse lesions. Fractures tended to be less conspicuous when they were acute and were more easily recognized with healing, especially with specimen radiography. Histologically, the fracture line consistently undercut the medial subperiosteal bone collar. Extension of hypertrophic chondrocytes from the growth plate into the region of fracture was found in all nine healing lesions. CONCLUSION: The classic metaphyseal lesion of the distal femur has distinctive radiologic and histopathologic characteristics that relate to the anatomy of the region. Because the distal femur is a common site for this strong indicator of infant abuse, the region should be carefully evaluated with well-collimated, high-detail skeletal radiographs in all cases of suspected infant abuse.

Case-Control Studies↗
PubMed1997

Combined pectoralis flap and gastric pull-up for pharyngeal reconstruction.

BACKGROUND: The gastric transposition flap, "gastric pull-up," is one of the standard techniques of reconstruction after total laryngopharyngectomy. Under certain circumstances, this method may provide insufficient tissue for a tension-free closure. In these circumstances, the surgeon could either close under tension, risking the viability of the flap and probable fistula; create a pharyngostome; or recruit additional tissue. In this article, we describe the use of the pectoralis major myocutaneous flap in combination with the gastric pull-up for reconstruction. METHODS: A retrospective review of three patients who underwent the procedure was performed, and a detailed description of the surgical technique is provided. RESULTS: The procedure was performed in three patients, all of whom healed without wound infection or fistula. CONCLUSIONS: The combination of a pectoralis flap with a gastric transposition is an alternative for cases in which a gastric flap alone is insufficient. With this combination virtually any defect of the upper aerodigestive tract can be successfully closed.

Humans↗
PubMed1997

Human anatomy: a foundation for education about death and dying in medicine.

In most medical schools, little curricular time is devoted to the art of medicine, and this is particularly evident with respect to death education. We make a case for including education on death and dying in medical schools, specifically its early introduction in the anatomy course. Studies indicate that whereas dissection of cadavers is an exciting discovery for most students, for many it is traumatic and if not addressed, students may use depersonalization and denial as their approach to suffering. The dissecting experiences in two different medical schools are described. The University of Massachusetts program developed in a traditional curriculum and explores humanistic issues with lectures and group discussions. Parallels are drawn between dissection and patient care, and coping styles are discussed openly. In the problem-based curriculum at Dalhousie Medical School, death and grief are discussed in the first week of medical school, and students are given information about the body donor program and support systems for students. This program is part of a longitudinal curriculum on death and dying. In both schools, students tour the dissecting rooms before the course begins and organize memorial events for body donors at the end of the academic year. These examples illustrate how death education can begin early in the medical curriculum and contribute to the development of practitioners who are sensitive to broader issues of human mortality.

Anatomy↗
PubMed1997

Variability of the obturator vessels.

The obturator artery and vein are usually described as branches or tributaries of the internal iliac vessels although variations with connections to the external iliac or inferior epigastric vessels have been reported. Because these anomalous vessels are at risk in groin or pelvic surgeries that require dissection or suturing along the pelvic rim, we measured the frequency of these variations in 105 pelvic walls (45 in the United States and 60 in China). Our data show that 70-82% of pelvic halves and 83-90% of whole pelves had an artery, vein, or both in the variant position. Arteries were most often found in the normal position only but normal and anomalous veins were most frequently found together. These data show that it is far more common to find a vessel coursing over the pelvic rim at this site than not and have implications for both pelvic surgeons and anatomists.

Adult↗
PubMed1997

Sphincters of canine hepatic sublobular veins respond to endothelin-1 and 3.

The dog has been used repeatedly as a model in liver transplantation research. The microcirculation and its regulatory mechanisms play a crucial role during ischemia and reperfusion. Little is known about the role of venous sphincters in regulating blood flow in the dog liver. Hence, we performed this study to elucidate their potential role in regulating local blood flow. In 14 dogs mean systemic (MSP) and mean portal venous pressure (MPP) were measured. Light and electron microscopy (scanning and transmission) of tissue sections and vascular corrosion casts were used to elucidate the microvascular morphology. Immunocytochemistry was applied to identify smooth muscle cells and the innervation of venous sphincters. Endothelins 1 and 3 were injected to find whether the hepatic venous sphincters are sensitive to these vasoactive agents. Tufts of smooth muscle cells were found in the sublobular veins (SLV; 100 to 250 microm in diameter), that reduced the luminal diameters of veins by 34%. Nerve endings were not observed close to these venous sphincters. The MSP and MPP were 75.3+/-2.4 mmHg and 8.9+/-0.95 mmHg, respectively. Treatment with 1.0 microg/kg of endothelin-1 (ET-1) significantly increased the MSP, the MPP and the percentage of focal venous sphincter contraction by 39% (105+/-4.7 mmHg), 43% (12.8+/-1.7 mmHg) and 57% (53.5+/-4.7), respectively (P <0.01). Treatment with ET-3 caused a significant (P <0.01) decrease in the MSP, the MPP and the percentage of sphincter contraction by 19% (61.0+/-2.2 mmHg), 39% (5.8+/-2.9 mmHg) and 38% (20.9%+/-3.15). Sinusoids did not contain sphincters. Hepatic arterioles and central veins were not affected by ET-treatment. The contraction of SLV sphincters correlated with increases in MPP (r=0.81, P <0.01) and was related to the MSP (r=0.67, P <0.01). These data show that the smooth muscle sphincters in SLV of the dog liver are involved in the local regulation of blood flow and that these sphincters are stimulated by non-neurogenic mechanisms. These sphincters contract in response to ET-1 and relax in response to ET-3. Since ET-1 is released during and/or causes inflammation, e.g., during ischemia and reperfusion, its antagonists might be of benefit during transplantation reperfusion of liver.

Actins↗
PubMed1997

The effects of colony-stimulating factor-1 on the number and ultrastructure of osteoclasts in toothless (tl) rats and osteopetrotic (op) mice.

The role of colony-stimulating factor-1 (CSF-1 or M-CSF) in osteoclast development is illustrated by observations that administration of exogenous CSF-1 increases osteoclast number and improves the skeletal sclerosis of two osteopetrotic mutations, toothless (tl) in the rat and osteopetrotic (op) in the mouse. We examined the effects of CSF-1 treatment on the number and ultrastructure of osteoclasts in the tibial metaphysis of normal and mutant animals of both stocks to understand the similarities and differences between these two mutations. Osteoclasts from normal animals of both stocks were abundant and possessed the ultrastructural features of active cells. These included apical areas in contact with mineralized surfaces with tightly apposed clear zones, extensive ruffled borders, and a vacuolated cytoplasm with numerous mitochondria. In toothless rats osteoclasts were difficult to locate and those present had poorly defined ruffled borders, fewer cytoplasmic vacuoles, and a basal membrane with both smooth and ruffled areas. Large lipid accumulations were often found near tl osteoclasts. Osteoclasts in op mice were difficult to find, but more numerous than in tl rats. Unlike tl osteoclasts, those of op mice possessed very well developed ruffled borders, small clear zones, and large electron-dense cytoplasmic inclusions. These cells also had unusual basal membranes with both smooth and ruffled regions. CSF-1 treatment increased the number of osteoclasts in both mutant stocks, normalizing the numbers in op mice, but not tl rats. CSF-1 injections caused dramatic changes in the morphology of tl osteoclasts, including increased incidence and size of ruffled borders and cytoplasmic vacuolization. The growth factor had little effect on ruffled borders or clear zones in op mice. Interestingly, mutant osteoclasts of both stocks exhibited a ruffled basal membrane in response to CSF-1 treatment. This increase in membrane ruffling may reflect the ability of CSF-1 to promote rapid formation of osteoclasts from mononuclear precursors in a more permissive microenvironment. Our data indicate that CSF-1 is not required for the development of at least some osteoclasts. The differences in response to CSF-1 treatment which we report lead us to speculate that additional factors may be involved in osteoclastogenesis.

Animals↗
PubMed1997

Ultrastructural evidence of abnormally short and maldistributed actin stress fibers in osteopetrotic (toothless) rat osteoblasts in situ after detergent perfusion.

Osteopetrosis is a heterogenous group of metabolic bone diseases characterized by a generalized increase in skeletal mass, the product of reduced bone resorption and interceptions in the development and/or function of osteoclasts. In one such mutation in the rat, toothless (tl), osteoblasts are absent from older bone surfaces and there is evidence for aberrant osteoblast gene expression and function. Given the emerging appreciation of the role of osteoblasts in the differentiation and activation of osteoclasts, we have examined ultrastructural features of the cytoskeleton of normal and mutant osteoblasts after perfusion fixation with the non-ionic detergent Triton X-100. This procedure reduces the electron density of the cytoplasm, rendering visible the microfilamentous network in osteoblasts. In normal osteoblasts a prominent system of stress fibers (bundles of actin microfilaments) run parallel to the cell membrane adjacent to osteoid surfaces, stretching for 75% of that distance. However, only 50% of mutant (tl) osteoblasts had stress fibers and in these cells stress fibers were either significantly shorter (18% of normal) or distributed intracellularly rather than along the osteoid surface. In mutant osteoblasts without stress fibers, 20% showed ultrastructural signs of cell degeneration. Given the role of stress fibers in cellular attachment ot extracellular matrices, these observations suggest that the reduced number of osteoblasts in tl rats may be related to their inability to organize actin filaments and adhesion plaques for attachment to bone surfaces. We propose that a feature of osteopetrosis in the tl rat is a disruption of the mechanisms that regulate the synthesis, sorting, and/or assembly of actin.

Actins↗
PubMed1997

Mucoceles of the maxillary sinus.

The maxillary sinus is an uncommon site for mucoceles within the paranasal sinuses. In this study nine patients with maxillary sinus mucoceles are presented. Six of these patients were treated by open approaches, and three were treated by endoscopic drainage alone. For uncomplicated maxillary sinus mucoceles, endoscopic drainage appears to be a reasonable approach, whereas for more complicated cases extending outside the sinus, open approaches may be required.

Adult↗
PubMed1997

Trace elements in head and neck cancer patients: zinc status and immunologic functions.

In this study we have assessed zinc status and zinc-dependent cell-mediated immune functions (interleukin-2 production by mononuclear cells, natural killer cell lytic activity, and interleukin-1 beta production by mononuclear cells) in adult patients with squamous cell carcinoma of the upper aerodigestive tract at diagnosis and before any therapy was instituted. Inasmuch as significant interactions between zinc, copper, and iron exist, we also assayed the plasma copper level, serum iron level, and total iron-binding capacity in our patients. We recruited 30 cancer subjects and 21 control subjects. On the basis of cellular zinc criteria, we diagnosed a mild deficiency of zinc in 53% of cancer subjects. The plasma zinc level was not decreased in our subjects. A univariate analysis was applied by use of one-way analysis of variance comparing study variables among the three study groups (controls and zinc-deficient and zinc-sufficient cancer patients) and Tukey's multiple comparison test, and we showed that interleukin-2 production and natural killer lytic activity were decreased in zinc-deficient cancer patients. Interleukin-1 beta production (ELISA assay) was increased in both zinc-deficient and zinc-sufficient groups. Plasma copper level was not different, but the iron utilization was decreased in both groups of cancer subjects. We conclude that zinc deficiency and zinc-dependent immunologic dysfunctions are present in more than half of the patients with head and neck cancer in the Detroit area.

Adult↗
PubMed1997

Endothelin-1 causes luminal constrictions in rat cochlear veins.

Serum levels of the vasoconstrictor endothelin-1 (ET-1) increase in ischemia and systemic hypertension. We examined the effects of ET-1 on the cochlear microvasculature. Blood vessels were cast with methacrylate in adult male Wistar Kyoto rats, 10 min after intravenous injection of ET-1 (1.0 microg/kg); control animals received saline. Systemic blood pressure was recorded continuously. ET-1 increased the average systolic pressure by 18% and average diastolic pressure by 22% (P < 0.01). Scanning electron microscopy of cast vessels showed multiple circumscribed luminal constrictions on: (1) postcapillary venules; (2) collecting veins; (3) where collecting veins merged with the spiral modiolar vein; (4) on the spiral modiolar vein itself. Circumscribed constrictions in arteries were not observed. In ET-1 injected animals focal contractions of collecting veins reduced luminal width by 13.4% +/- 2.9 (P < 0.01). In control rats, constrictions on venous casts were minimal and constrictions on arteries were not observed. The present study shows that ET-1 is involved in local control of cochlear blood flow in that it focally contracts cochlear veins. It is suggested that this might be due to the high affinity of ET-1 receptors and/or the large number of ET-1 receptors on contractile cells in venous walls.

Animals↗
PubMed1997

Alteration of mineral crystallinity and collagen cross-linking of bones in osteopetrotic toothless (tl/tl) rats and their improvement after treatment with colony stimulating factor-1.

A common feature of various types of mammalian osteopetroses is a marked increase in bone mass accompanied by spontaneous bone fractures. The toothless (tl/tl) rat osteopetrotic mutation is characterized by drastically reduced bone resorption due to a profound deficiency of osteoclasts and their precursors. An altered bone morphology has also been observed. The mutants cannot be cured by bone marrow transplantation, but skeletal defects are greatly reduced after treatment with colony stimulating factor 1 (CSF-1). The objectives of this study were to characterize mineral and collagen matrices in cancellous and compact bone isolated from long bones of 6-week-old normal littermates, tl/tl osteopetrotic mutants and mutants (tl/tl) treated with CSF-1. There were no differences in bone mineral content, but a significant decrease in the crystallinity of mineral evaluated by the method based on electron paramagnetic resonance spectrometry was observed in all bones of tl/tl mutants as compared to that of controls. Within the collagen matrix, slight decreases in the labile cross-links, but significant increases in the content of the stable cross-links, pyridinoline, and deoxypyridinoline, were observed in both cancellous and compact bone of osteopetrotic mutants. In tl/tl mutants treated with human recombinant CSF-1, the normalization of the crystallinity of bone mineral as well as collagen cross-links was found. Our results indicate that remodeling of bone matrix in tl/tl mutants is highly suppressed, but that after treatment with CSF-1, this activity recovers significantly. Taken together, these data provide further support for the hypothesis that CSF-1 is an essential factor for normal osteoclast differentiation and bone remodelling.

Animals↗