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Biomedical subjects

L C Anderson

Publications and source records attributed to L C Anderson.

At least 19 recordsLinked to original sources

Differential secretion of proteins by rat submandibular acini and granular ducts on graded autonomic nerve stimulations.

1. The influence of graded parasympathetic and sympathetic nerve stimulations on the secretion of protein from rat submandibular gland was studied. Peroxidase was used as a marker for the acini and rat tissue kallikrein (official nomenclature rK1) as the marker for granular ducts. Tonin (rK2) was also measured, and the ratio of rK2:rK1 was calculated as an indication of the cellular route of secretion. 2. Continuous parasympathetic nerve stimulation caused a copious flow of saliva that had a low protein content. The secretion of peroxidase (acini) showed a gradual moderate increase as the frequency increased. However, the concentrations of rK1 and rK2 (granular ducts) showed little change throughout, and the ratio of rK2:rK1 remained relatively constant. 3. Graded sympathetic stimulation was applied against a background of parasympathetic stimulation. Secretion of peroxidase was increased by the addition of 0.1 Hz continuous sympathetic stimulation. The amount increased thereafter up to 2 Hz, but showed no further increase if the stimulation was applied as bursts of 10 or 20 Hz. In comparison, the secretion of proteinase activity showed little change with superimposed continuous sympathetic stimulation, and the rK2:rK1 ratio was similar to that in saliva produced by parasympathetic stimulation alone. Sympathetic stimulation applied in bursts, however, caused a large increase in the secretion of proteinase activity, and with 20 Hz burst stimulation the rK2:rK1 ratio was indistinguishable from that of sympathetic saliva per se. There was an augmented secretion of both peroxidase and kallikrein when 20 Hz burst stimulation was combined with parasympathetic stimulation. The effects of sympathetic stimulation were abolished by alpha- and beta-adrenoceptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Revision total hip replacement using the S-ROM femoral component.

The proximally porous-coated, modular S-ROM femoral component was used in 52 complex total hip revisions done in 48 patients. These patients had severe bone loss, leg length inequality, and instability. Twenty-two patients required structural femoral allografts; 8 had previous resection arthroplasties for sepsis. The mean number of previous hip operations was 3. The stem was press fit, and the metaphyseal sleeve was selectively cemented to the allograft. The preoperative Harris rating was 44 points; at a mean of 3 years, followup was 82 points. Eighty-four percent of the patients were satisfied with their outcomes. No radiographic or histologic evidence of fretting at the modular sleeve-stem junction or along the stem was seen. Significant thigh pain persisted in 2 patients and was directly related to stem diameters > 17 mm. Complications in these complex cases were not infrequent, reflecting the need for allograft augmentation, and included greater trochanter bursitis and nonunion in 20 hips, minor nonpropagating fracture in 13 hips, and 12 dislocations. Mechanical loosening occurred in 5 hips. There were no complications attributable to the S-ROM modular femoral component, and the prosthesis has proven to be versatile and did well in these very difficult cases.

Adult

Morphological effects of diabetes on the granular ducts and acini of the rat submandibular gland.

Effects of experimental diabetes on rat submandibular glands have been documented, but earlier reports suggested that diabetes caused an extensive cellular degeneration and a replacement of the parenchymal cells by fibrous connective tissue. Such observations, however, are difficult to reconcile with the relatively normal physiological responsiveness of the gland (Anderson and Suleiman, 1989). This study, therefore, reexamined the histological, histochemical and ultrastructural effects of streptozotocin-induced diabetes on rat submandibular glands. The tissues were examined at 3 weeks, and 3 and 6 months after the induction of diabetes, and compared with glands from age-matched controls by both light and electron microscopy. Light microscopically, the proportional volumes of the acini and granular ducts remained constant in control rats at about 48% and 38% respectively. In diabetic animals the volume density of the acini increased progressively to 62%, whereas that of the granular ducts decreased to 20%. The diameter and number of granular ducts were reduced in diabetic animals, but acinar cell profile area was only affected 6 months after the induction of diabetes. Ultrastructurally, there was an accumulation of lipid in the acinar cells and, with increasing duration of diabetes, the number of autophagic structures in both the acini and the granular ducts increased. Although there was evidence of some cellular degeneration it was never excessive. Morphometry showed that the volume density of secretory granules within the acinar cells was unaffected, but there was a significant reduction in the volume density of secretory granules within the granular ducts. Thus, in the rat submandibular gland the greatest effect of streptozotocin-induced diabetes was to cause hypotrophic changes in the cells of the granular ducts. The relative contributions of a direct effect of insulin insufficiency and the hypogonadal effects of diabetes, however, are not known.

Animals

The effects of streptozotocin diabetes on salivary-mediated bacterial aggregation and adherence.

Diabetic rats are known to have an increased susceptibility to dental caries and major alterations in parotid salivary composition. Salivary proteins play an important part in oral health maintenance; thus specific changes in salivary protein composition in diabetic animals might alter the ecological balance in favour of cariogenic bacteria, and toward the initiation and progression of the disease process. The ability of whole, parotid and submandibular salivas from control and streptozotocin-diabetic rats to mediate the aggregation and adherence to hydroxyapatite of mutans streptococci was examined. Salivary-mediated bacterial aggregating activity was significantly reduced in whole and parotid salivas from diabetic rats, but bacterial adherence to hydroxyapatite was unaffected. The aggregating and adherence activities of rat whole saliva were derived mainly from parotid saliva, which contains predominantly low molecular-weight proteins and glycoproteins (< 200 kDa), but rat parotid saliva was capable of interacting with the bacterial receptor for the high molecular-weight aggregating factor in human saliva. SDS-PAGE of parotid saliva revealed that a number of proteins, including the basic and acid proline-rich proteins, were altered in the salivas of diabetic animals. After incubation with either Streptococcus mutans or hydroxyapatite several protein bands were depleted, and thus a variety of proteins and glycoproteins may be responsible for the adherence and aggregating activity of rat parotid saliva.

Analysis of Variance

Relative importance of emergency medical system transport and the prehospital electrocardiogram on reducing hospital time delay to therapy for acute myocardial infarction: a preliminary report from the Cincinnati Heart Project.

Substantial time delays from symptom onset to diagnosis and treatment of patients with acute myocardial infarction have been demonstrated. To determine the relative importance of prehospital mode of patient transport and the relative impact of emergency medical system transport with or without a prehospital cellular electrocardiogram (ECG) on hospital time delays to initiation of thrombolytic therapy, four prospective parallel groups of patients with acute myocardial infarction were evaluated. The median hospital time delay to treatment median (twenty-fifth and seventy-fifth percentiles) was 64 minutes (46 and 87 minutes, respectively, for twenty-fifth and seventy-fifth percentiles) for patients transported by private automobile ("walk-in"); 55 minutes (45 and 68 minutes, respectively) for patients transported by local ambulance; 50 minutes (38 and 81 minutes, respectively) for patients transported by the emergency medical system without a prehospital ECG; and 30 minutes (27 and 35 minutes, respectively) for patients transported by the emergency medical system who had a 12-lead ECG transmitted from the field. Patients transported by the emergency medical system were randomized to receive cellular telephone transmission of a prehospital 12-lead ECG. Specialized emergency medical system transport alone did not facilitate in-hospital initiation of thrombolytic therapy in patients with acute myocardial infarction when compared with those brought by local ambulance or by private automobile. A significant reduction in hospital time delay to treatment was observed only in patients transported by the emergency medical system who had cellular transmission of a prehospital 12-lead ECG from the field.

Electrocardiography

Effects of streptozotocin diabetes on amylase release and cAMP accumulation in rat parotid acinar cells.

Rat parotid responses to sympathetic nerve stimulation in vivo are impaired 2-4 weeks after the induction of streptozotocin diabetes. In this study, the effects of experimental diabetes of similar duration and severity on noradrenaline-stimulated amylase release and cAMP accumulation were examined in vitro. Amylase levels were significantly lower in acinar cells isolated from diabetic animals than in controls, and cellular amylase increased after treatment of the diabetic animals with either thyroxine (T4) or insulin. Diabetes and T4 had no apparent affect on amylase release measured as a percentage of the total. In contrast, giving insulin resulted in a significant reduction in maximal secretion (20.4 +/- 2.4% compared with 43.6 +/- 7.6%). Similar results were observed when amylase release was stimulated with forskolin. Basal cAMP levels were unaffected by diabetes or T4 (7.8 +/- 2.3 pmol/mg protein), but stimulated cAMP levels were significantly greater in diabetic acinar cells than in controls. Insulin reversed the effects of diabetes on cAMP accumulation, whereas T4 had no effect. Thus, diabetes (2-4 weeks) and insulin in vivo appear to have paradoxical effects on parotid amylase release and cAMP accumulation in vitro. Further, the effects of diabetes appear to be unrelated to thyroid status.

Amylases

Changes in the lectin-binding of capillaries in rat salivary glands after streptozotocin-induced diabetes.

The lectin-horseradish peroxidase conjugate of GSA I-B4 (Griffonia simplicifolia isolectin) has some binding affinity with capillary walls in sections of the major salivary glands from normal rats. After inducing diabetes with streptozotocin a conspicuous increase in the staining intensity with GSA I-B4 was already evident in parotid capillaries at 3 weeks and this increase persisted at 3 and 6 months. In submandibular capillaries, however, an increased uptake of GSA I-B4 was evident only at 6 months after inducing diabetes. The reasons for these different time scales in the two glands are not known but the increased uptake of GSA I-B4, which is due to an increase in carbohydrate-containing sites with available terminal alpha-D-galactose, is considered to reflect a pathological change.

Animals

Lipid analysis of the major salivary glands in streptozotocin-diabetic rats and the effects of insulin treatment.

Two separate sets of experiments were performed on female Wistar rats made diabetic with streptozotocin: (1) a time-course study where groups of three animals were removed at weekly intervals, up to 4 weeks after induction of diabetes, with an age-matched group of control (normal) animals kept for 4 weeks; (2) six further animals were made diabetic and kept for 7 weeks; three of these were given insulin in the final week. At the required time the animals were anaesthetized and the salivary glands removed and preserved by fixation or freezing. The frozen tissues were later homogenized and the protein and lipid content analysed. Histologically, intracellular lipid droplets had accumulated in the majority of the diabetic salivary glands. In the time-course experiment, the visible amount of intracellular lipid reached a maximum after 2 weeks and then decreased, with a concomitant disappearance of interstitial lipid. The increased lipid content was not attributable to any one class. The fatty acid profiles of the glands showed an increase in the percentages of C18:0 (stearic acid) and C18:2w6 (linoleic acid) and a decrease in the percentages of C18:1w9 (oleic acid) and C20:4w6 (arachidonic acid). After 1 week of insulin treatment the lipid content and the fatty acid profiles returned to normal. Thus the effect of insulin on salivary gland lipid metabolism is rapid both in its occurrence and reversibility. The effects seen in the diabetic rats are considered to be due to a lack of insulin and not to the presence of streptozotocin.

Animals

Secretory oedema in diabetic submandibular glands during parasympathetic nerve stimulation: relationship to microvascular abnormalities in streptozotocin-treated rats.

1. Submandibular secretion during parasympathetic stimulation (5 Hz) was examined in streptozotocin-diabetic and age-matched control rats. 2. At 3 weeks, but not 3 and 6 months, flow rate was initially greater than in controls, but it declined rapidly after 30 min. 3. The reduction in flow rate was associated with oedema of the gland. 4. At 3 months, graded stimulation revealed a tendency to oedema at frequencies of 10 Hz and above. 5. Morphologically, submandibular capillary density was increased in diabetic rats. 6. Thus, in diabetes the submandibular gland appears less able to withstand continuous parasympathetic stimulation, due in part to an increase in tissue capillary area.

Animals

Secretory responses in granular ducts and acini of submandibular glands in vivo to parasympathetic or sympathetic nerve stimulation in rats.

The roles of sympathetic and parasympathetic nerves in the secretion of saliva from submandibular glands of rats have been tested by electrical stimulation of either nerve for 1 h unilaterally in separate animals. The flows of saliva thereby induced and their protein content were monitored. Structural changes in each gland were assessed by light- and electron microscopy and compared with the unstimulated contralateral control gland, and the extent of the changes was determined morphometrically. Sympathetic nerve stimulation induced a relatively low flow of saliva that was rich in protein and was accompanied by extensive degranulation from both acinar and granular duct cells. In contrast parasympathetic nerve stimulation induced a considerable flow of saliva that had a low protein content and no detectable degranulation occurred from the secretory cells. It is possible, therefore, that some protein in parasympathetic saliva may have arisen from a non-granular pathway.

Animals

Rat sublingual salivary glands: secretory changes on parasympathetic or sympathetic nerve stimulation and a reappraisal of the adrenergic innervation of striated ducts.

Sublingual glands were examined by light and electron microscopy after stimulating the parasympathetic nerve (5 Hz continuously) or the sympathetic nerve (50 Hz in bursts 1 s every 10 s) and compared with contralateral, unstimulated, normal glands from each animal. Parasympathetic stimulation caused secretion of mucin from the tubulo-acini and possibly a small amount of degranulation from the demilunes but no changes were detected in the striated ducts. Sympathetic stimulation, on the other hand, had no effect on the tubulo-acini or demilunes but caused a surprisingly extensive degranulation of the striated ducts plus loss of glycogen from their cells. Reassessment of the adrenergic innervation in the glands was therefore undertaken, by means of catecholamine fluorescence. This identified a regular association between adrenergic nerves and the striated ducts not only in sublingual but also in submandibular glands; features that have not previously been recognized. There was, however, only a sparse adrenergic innervation of the other parenchymal elements in the sublingual glands.

Animals

Effects of diabetes and dietary manipulation on rat parotid gland secretory response to sympathetic nerve stimulation.

1. The effects of streptozotocin-diabetes, bulk-diet, low protein diet (8%) and protein-calorie malnutrition on parotid gland response to sympathetic nerve stimulation were studied in male Wistar rats. 2. Mean body weights were considerably less in diabetic and protein-calorie malnourished rats than in the other groups, but parotid gland weight was reduced only in animals placed on a low-protein diet. 3. Salivary flow rate (microliter/min/g tissue) and total protein output (mg secreted/g tissue) were reduced in diabetic rats. 4. Salivary composition was altered in diabetes and protein-calorie restriction, and the specific changes were unique to each condition. 5. Thus, with the possible exception of gland weight the effects of diabetes on parotid gland structure and function are not related to either hyperphagia or nutritional status.

Animals

A review of the intraosseous course of the nerves of the mandible.

A review of the literature revealed that a common feature of all human mandibles is a large nerve (inferior alveolar nerve, IAN) between the mandibular and mental foramina. This nerve sends branches directly to the teeth or contributes a variable number of branches to a plexus of nerves which does the same. The plexus originates from a separate nerve that enters the mandibular foramen. The nerve plexus has been demonstrated by dissections and not by radiology. The buccal-lingual and superior-inferior positions of the IAN were not consistent among mandibles. The intramandibular IAN frequently ran a concave curve with a posterior segment descending as it progressed anteriorly and an anterior segment that ascended to the mental foramen. A bony canal was not always observed between the mandibular and mental foramina. The canal frequently lacked definite walls, especially near the mental foramen. Bilateral symmetry (location of the canal in each half of the mandible) was common, whereas duplications of the canal were rare. Nutrient canals and other branches of the mandibular nerve have been observed within the mandible. These may have been confused for the IAN or may contribute to the plexus of nerves.

Humans

Time delays in the diagnosis and treatment of acute myocardial infarction: a tale of eight cities. Report from the Pre-hospital Study Group and the Cincinnati Heart Project.

To establish the magnitude of prehospital and hospital delays in initiating thrombolytic therapy for acute myocardial infarction, the time from telephone 911 emergency medical system (EMS) activation to treatment and its components were analyzed from eight separate ongoing trials. This included estimates of ambulance response time, prehospital evaluation and treatment time, and time from admission to the hospital to initiation of thrombolytic therapy. The average time from EMS activation to patient arrival at the hospital was prospectively determined to be 46.1 +/- 8.2 minutes in 3715 patients from eight centers. The time from admission to the hospital to initiation of thrombolytic therapy was retrospectively determined to be 83.8 +/- 55.0 minutes in a separate group of 730 patients from six centers. Both the prehospital and hospital time delays were much longer than those perceived by paramedics and emergency department directors. Shorter hospital time delays were observed in patients in whom a prehospital ECG was obtained as part of a protocol-driven prehospital diagnostic strategy and a diagnosis of acute infarction made before arrival at the hospital (36.3 +/- 11.3 minutes in 13 patients). These results show that the magnitude of time required to evaluate, transport, and initiate thrombolytic therapy will preclude initiation of treatment to most patients within the first hour of symptoms. Implementation of a protocol-driven prehospital diagnostic strategy may be associated with a reduction in time to thrombolytic therapy.

Electrocardiography

Morphological effects of sympathetic nerve stimulation on rat parotid glands 3-4 weeks after the induction of streptozotocin diabetes.

Male Wistar rats were fasted overnight and anaesthetized 3-4 weeks after the induction of streptozotocin diabetes. The right parotid ducts were cannulated, and parotid salivary flow was induced by stimulating the sympathetic trunk in bursts (50 Hz, 1:10). Stimulated and unstimulated glands were weighed, fixed for morphometric analysis, and assayed for total protein and amylase. Gland weights did not differ between diabetic and control rats. Nevertheless, total protein (6.17 +/- 5.40 mg) and amylase (1.32 +/- 0.49 mg) output from the gland were reduced in diabetic animals compared with controls (13.73 +/- 2.81 and 3.41 +/- 0.51 mg, respectively). Morphometric analysis of unstimulated glands showed no differences in either acinar cell profile area, or in the number of secretory granule profiles/cell in unstimulated glands. Upon sympathetic stimulation, however, the depletion of granule profiles was significantly less in diabetic than in control rats. Finally, the mean diameter of secretory granules was significantly less in diabetic (0.89 +/- 0.05 microM) than in control (1.04 +/- 0.06 microM) glands.

Amylases

Fate of patients with acute myocardial infarction with patency of the infarct-related vessel achieved with successful thrombolysis versus rescue angioplasty.

Patients with failure of infarct-related artery recanalization after thrombolytic therapy have a poor clinical outcome. These patients have been considered for rescue angioplasty 90 min after thrombolytic therapy at the time of emergency catheterization in the course of five Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) trials. The outcome of 776 patients with patent infarct-related vessels after emergency catheterization was analyzed--607 with thrombolysis-mediated patency of the infarct-related vessel and 169 with patency achieved by angioplasty. Baseline characteristics of the thrombolysis and angioplasty patency groups were similar except for a higher acute left ventricular ejection fraction (51.3% versus 48.2%) in the thrombolysis group (p = 0.003). Seven to 10 day left ventricular ejection fraction was higher (52.3% versus 48.1%), infarct zone functional recovery was greater (0.44 versus 0.21 standard deviation/chord, or 18% versus 7%, p = 0.001) and reocclusion was less (11% versus 21%) in the thrombolysis compared with the angioplasty group. Despite these differences, angioplasty patency was associated with the same low in-hospital mortality rate (5.9% versus 4.6%) and long-term mortality rate (3% versus 2%) as thrombolysis patency. Reocclusion adversely affected the mortality rate and ventricular functional recovery. Technical failure of rescue angioplasty was associated with a much higher mortality rate than was technical success (39.1% versus 5.9%). Thrombolysis patency was preferable to angioplasty patency after thrombolytic therapy in acute myocardial infarction, but both were associated with the same low in-hospital and long-term mortality rates, suggesting that rescue angioplasty is beneficial in some patients with failure of infarct-related artery recanalization after thrombolytic therapy.

Angioplasty, Balloon, Coronary

Favorable early and long-term prognosis following coronary bypass surgery therapy for myocardial infarction: results of a multicenter trial. TAMI Study Group.

Coronary bypass surgery was performed before hospital discharge on 82 (21%) of 386 consecutive patients enrolled in the Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) multicenter trial of intravenous tissue plasminogen activator and coronary angioplasty for acute myocardial infarction. Time from infarct symptom onset to coronary bypass surgery was 7.3 +/- 1.9 hours for 24 patients operated upon on an emergency basis and 9.3 +/- 5.2 days for 58 patients having late in-hospital surgery. There were no operative deaths and five in-hospital deaths in the surgical group, all of which occurred in patients with preoperative cardiogenic shock. Although patients in the surgical group were older (59.7 +/- 10.4 years versus 54.9 +/- 10.2 years; p = 0.03), had more extensive coronary artery disease (42% three-vessel disease versus 11%; p = 0.001), and had a higher incidence of anterior wall myocardial infarction (48% versus 39%; p = 0.02), in-hospital mortality for the surgical group (6%) was similar to that in 301 patients not undergoing surgery (7%) in this trial. For patients discharged from the hospital, mortality at 1 year was 2.5% in the surgical group and 1.8% in patients not having coronary bypass surgery before hospital discharge. At a 1 year follow-up, there were no significant differences in the frequency of cardiac or noncardiac-related hospitalizations or in event-free survival between surgical and nonsurgical groups. The majority of patients in both groups considered themselves to be in excellent or good condition. Coronary bypass surgery can be performed with low morbidity and mortality rates in close temporal association to acute myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon

Alpha-aminoisobutyric acid transport in isolated rat submandibular salivary acinar cells.

Na+-dependent alpha-aminoisobutyric acid (AIB) transport by isolated submandibular cell aggregates (pmol min-1 mg protein-1) was greater in the presence than in the absence of insulin, Vmax (5220 compared with 2900). Km (1.78 and 1.40 mM, respectively) was unaffected by insulin. Na+-dependent methyl-aminobutyric acid (MeAIB) transport was also greater in the presence of insulin (V max, 3120 compared with 2010 pmol min-1 mg protein-1; Km, 1.03 and 0.93 mM). In the presence of 10 mM MeAIB, Na+-dependent AIB transport was reduced to 76 pmol min-1 mg protein in both control and insulin-treated cells. The remaining Na+-dependent uptake of AIB was inhibited by 10 mM serine. Na+-independent AIB transport was unaffected by insulin, and in the presence of 5 mM 2-aminobicyclo-[2,2,1]-heptane-carboxylic acid (BCH) AIB uptake was reduced to 10% of that observed under Na+-replete conditions. In the absence of insulin, the rate of Na+-dependent AIB uptake rapidly decayed; however, following the addition of hormone the rate of transport was maintained. Thus in the rat submandibular gland AIB uptake is mediated by at least three transport systems (A, L and ASC), and maintenance of normal system A activity requires insulin.

Aminoisobutyric Acids