Anterior cervical fusion using the IntExt combined cage/plate.

PURPOSE: To review our first 30 patients who underwent anterior cervical fusion using IntExt and xenograft. METHODS: Records of 23 men and 7 women aged 18 to 83 (mean, 40) years were reviewed by a single researcher. 23 patients had traumatic fracture-dislocations and 7 had degenerative disease. Pain, range of movement, neurological status, return-to-work status, kyphosis, and lordosis were recorded. Radiography and computed tomography were used to assess integration of the xenograft with the host bone, intervertebral fusion around the cage, and any screw loosening. RESULTS: The mean follow-up duration of the 30 patients was 14 (range, 1-47) months. There was no evidence of screw loosening or breakage. 20 of the 28 patients had no neck pain. Radiographs and/or computed tomographic scans of 23 patients showed bone union or clinical evidence of stability. CONCLUSION: The IntExt is effective in stabilising traumatic fractures. Although the literature does not support single-level plating in degenerative fractures (because of high success rates with autologous bone grafting), the IntExt has advantages of avoiding grafting complications, donor-site morbidity, and resorting to a postoperative collar.

Ursodeoxycholic acid action on the transport function of the small intestine in normal and cystic fibrosis mice.

Ursodeoxycholic acid possesses choleretic and cytoprotective properties and in cystic fibrosis (CF) it is used to treat the hepatobiliary symptoms of the disease. This study investigated the effects of this bile acid on the transport function of the small intestine in normal and CF mice. The effects of ursodeoxycholic acid were monitored as changes in short-circuit current (SCC) in stripped sheets of small intestine from normal (Swiss MF1) and transgenic CF (Cftr(tm2Cam)) mice. In ileal sheets from Swiss MF1 mice, mucosal ursodeoxycholic acid caused a biphasic increase in SCC. The first phase was reduced by lowering the mucosal Na+ concentration, while the second phase was inhibited by (Cl-)-free conditions, serosal furosemide or mucosal diphenylamine-2-carboxylic acid (DPC), suggesting an initial Na+-dependent bile acid absorption followed by a stimulation of electrogenic Cl- secretion. Serosal application of ursodeoxycholic acid to the ileum and mucosal or serosal application to the mid-intestine and jejunum elicited a secretory response only. Secretion was Ca2+-dependent, but did not involve neural mechanisms. Mucosal mast cells, histamine and serotonin (5-HT) were implicated in the secretory response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 mice, but the secretory response to mucosal or serosal application of the bile acid was impaired in CF tissues. In ilea from CF mice the initial absorptive phase of the response to mucosal ursodeoxycholic acid was still observed. It is concluded that ursodeoxycholic acid induces secretion throughout the murine small intestine by a mechanism that involves degranulation of mucosal mast cells. In the ileum Na+-dependent absorption can also be detected. The secretory response is defective in CF intestine, but the absorptive effect is still present.

Taurocholic acid-induced secretion in normal and cystic fibrosis mouse ileum.

Bile acids cause secretion throughout the intestinal tract and this process contributes to maintaining the fluidity of intestinal contents. In cystic fibrosis (CF) defective intestinal secretion can lead to excessive dehydration of the luminal contents and the development of clinical symptoms. This study was designed to investigate bile acid-induced secretion in mouse ileum and to determine whether this process was defective in CF. Taurocholic acid-induced secretion was monitored as a rise in short-circuit current (SCC) in ileal sheets from normal (Swiss MF1) and transgenic CF mice. Taurocholic acid increased the SCC in both intact and stripped ileal sheets from Swiss MF1 mice. This effect was due to a stimulation of electrogenic Cl- secretion as it was inhibited by Cl(-)-free conditions, serosal furosemide (frusemide), mucosal diphenylamine-2-carboxylic acid (DPC) and increased serosal K+ concentration, without being affected by reduced mucosal Na+ concentration. Taurocholic acid-induced secretion was inhibited by tetrodotoxin, indicating the involvement of a neural pathway, but this did not include capsaicin-sensitive afferent neurons or muscarinic cholinoreceptors. Mucosal mast cells also contributed to the response. Responses in tissues from transgenic wild-type mice were similar to those obtained with Swiss MF1 animals, but ilea from CF mice exhibited a lower basal SCC with significantly reduced secretory responses to acetylcholine and taurocholic acid. We concluded that taurocholic acid induces ileal secretion by a mechanism that entails activation of enteric nerves and degranulation of mucosal mast cells. Impaired bile acid-induced secretion in CF may contribute to luminal dehydration.

Acetylcholine induces cytosolic Ca2+ mobilization in isolated distal colonic crypts from normal and cystic fibrosis mice.

In intestinal biopsies from cystic fibrosis (CF) patients acetylcholine fails to elicit a chloride secretion response, and this observation can be explained by a defect in the Ca2+ signalling pathway in CF secretory cells. We tested the hypothesis that in CF intestine, the generation of an intracellular Ca2+ signal upon cholinergic stimulation is absent. A transgenic CF mouse model was used. Electrical measurements on intact jejunum and unstripped colon were performed in Ussing chambers. Intact distal colonic crypts were isolated, and the intracellular Ca2+ concentration was monitored using the Ca2+-sensitive dye fura-2. Acetylcholine increased the short-circuit current generated by wild-type jejunum and colon, but failed to induce a response in CF tissues. Acetylcholine caused a transient elevation in the intracellular Ca2+ concentration in colonic crypts from both wild-type and CF mice; the amplitude and timing of the response in CF crypts was indistinguishable from that in wild-type crypts. The response to acetylcholine was also observed in the absence of extracellular calcium, indicating intracellular stores as the source from which the cytosolic Ca2+ concentration increased. We conclude that the absence of a cholinergically-induced secretory response in CF intestine is not due to a defect in the generation of a Ca2+ signal in intestinal cells upon cholinergic stimulation.

Effect of loperamide on Na+/D-glucose cotransporter activity in mouse small intestine.

The mu-opioid agonist loperamide is an antidiarrhoeal drug which inhibits intestinal motility and secretion. Its anti-absorptive effects are less well investigated, but may be mediated through calmodulin. We have investigated further the effect of loperamide on the intestinal Na+-dependent D-glucose transporter (SGLT1). Brush-border membrane vesicles were prepared from mouse small intestine, and uptake of [3H]glucose was measured. Na+-dependent glucose uptake displayed the typical overshoot at 34 s; the peak value was 1.6 nmol mg(-1). The overshoot disappeared in the presence of phlorizin or when Na+ was replaced by K+. Extravesicular loperamide dose-dependently inhibited SGLT1 activity with an IC50 value of 450 micromol L(-1). Loperamide displayed a mixed inhibition type: the apparent Vmax decreased from 0.9 to 0.5 nmol mg(-1)/15 s, the apparent Km increased from 0.23 to 1.13 mmol L(-1) glucose. Na+ kinetics were more complex, but loperamide inhibited net glucose uptake by 90% at 100 mmol L(-1) Na+. Glucose uptake was unchanged by agents affecting calmodulin activity. Loperamide inhibited intestinal Na+, K+-ATPase activity, whilst sucrase activity was unaffected. SGLT1 activity was inhibited by loperamide, but this effect was not mediated through calmodulin. As this action is only evident at high concentrations of loperamide a nonspecific mechanism may be involved.

The action of 5-hydroxytryptamine on normal and cystic fibrosis mouse colon: effects on secretion and intracellular calcium.

The ability of mouse colon to generate a secretory response to stimulation by 5-hydroxytryptamine (5-HT) was investigated in intact colonic sheets mounted in Ussing chambers. A preparation of intact isolated crypts was used to determine whether 5-HT action was associated with an elevation of cytosolic calcium levels, measured using the calcium-sensitive fluorescent dye, fura-2. 5-HT increased the short-circuit current, an effect that was inhibited by 55% in the absence of chloride and by 83% in the presence of serosal frusemide, consistent with the stimulation of electrogenic chloride secretion. This was confirmed by the observation that colonic tissue from transgenic cystic fibrosis mice (n = 4) failed to respond to 5-HT, although wild-type tissues generated an increased short-circuit current of 52.4+/-1.1 microAcm(-2) (n = 9). The electrical response to 5-HT was calcium-dependent. 5-HT action was unaffected by tetrodotoxin and was not mimicked by the 5-HT3 agonist 1-phenylbiguanide, indicating that neural mechanisms are not involved. The cyclooxygenase inhibitor indomethacin, however, reduced the 5-HT-induced rise in short-circuit current by 73%, suggesting that prostaglandin production contributes to the response. Stimulation of crypts with acetylcholine elicited an increase in cytosolic calcium levels, but no such response was detected on application of 5-HT (10(-6) to 10(-4) M), suggesting that 5-HT does not directly modulate intracellular calcium in colonic crypt cells. It is concluded that mouse colon responds to 5-HT challenge with a stimulation of electrogenic chloride secretion and that this effect is mediated by indirect mechanisms that might involve immune elements within the colonic wall.

Diaphyseal medullary stenosis with malignant fibrous histiocytoma: a hereditary bone dysplasia/cancer syndrome maps to 9p21-22.

Diaphyseal medullary stenosis with malignant fibrous histiocytoma (DMS-MFH) is an autosomal dominant bone dysplasia/cancer syndrome of unknown etiology. This rare hereditary cancer syndrome is characterized by bone infarctions, cortical growth abnormalities, pathological fractures, and eventual painful debilitation. Notably, 35% of individuals with DMS develop MFH, a highly malignant bone sarcoma. A genome scan for the DMS-MFH gene locus in three unrelated families with DMS-MFH linked the syndrome to a region of approximately 3 cM on chromosome 9p21-22, with a maximal two-point LOD score of 5.49 (marker D9S171 at recombination fraction [theta].05). Interestingly, this region had previously been shown to be the site of chromosomal abnormalities in several other malignancies and contains a number of genes whose protein products are involved in growth regulation. Identification of this rare familial sarcoma-causing gene would be expected to simultaneously define the cause of the more common nonfamilial, or sporadic, form of MFH-a tumor that constitutes approximately 6% of all bone cancers and is the most frequently occurring adult soft-tissue sarcoma.

Social Security fixes--beware of conjurers!

Among the many proposals for reform, there is one that offers the best chance of truly solving Social Security's financial problems, these authors believe. That proposal would increase savings by requiring workers to invest an additional 2% of their covered wages in individual accounts. At retirement, 75% of the money would go toward buying the current level of Social Security benefits, and 25% would be given to the individual as an "extra" pension. Individuals, not the government, would control investment of these accounts.

Effects of 5-hydroxytryptamine on the transintestinal electrical activity and cardiovascular function of fawn-hooded rats in-vivo.

Fawn-hooded rats, which have abnormal serotonergic function, were used to investigate the receptors involved in 5-hydroxytryptamine (5-HT)-induced intestinal secretion. The effects of 5-HT on secretion by the small intestine and proximal colon, monitored as increased transintestinal electrical activity, and on cardiovascular function, measured as changes in heart rate and blood pressure, were compared in fawn-hooded and Wistar rats. The maximum fall in heart rate induced by 5-HT (mediated by 5-HT3 receptors) was greater in fawn-hooded than in Wistar rats. ED50 values (the doses resulting in 50% of the maximum effect) for the 5-HT2-mediated increases in systolic pressure were lower for both 5-HT and 5-methoxytryptamine in the fawn-hooded group. The prolonged fall in diastolic pressure mediated by 5-HT1-like receptors was significantly attenuated in fawn-hooded rats, with the maximum responses to 5-HT, 5-methoxytryptamine and 6-hydroxyindalpine reduced to 21%, 42% and 28%, respectively, of the values obtained for Wistar rats. In fawn-hooded rats the small intestine was less sensitive to the effects of 5-HT (ED50 = 47 nmol kg(-1); ED50 for Wistar rats = 23 nmol kg(-1)) and the maximum colonic response to 5-methoxytryptamine was greater (7.0 mV compared with 4.3 mV in Wistar rats), but other indices did not differ for the two strains. The responses to 6-hydroxyindalpine were similar in fawn-hooded and Wistar rats. It is concluded that although the cardiovascular response of fawn-hooded rats to 5-HT challenge is very different from that of Wistar rats, this difference is not reflected in marked alterations in 5-HT-induced intestinal secretion. This is consistent with 5-HT stimulating secretion via the activation of several different receptor subtypes so that any changes in the receptor profile in fawn-hooded rats results in little alteration in the overall intestinal response.

5-Hydroxytryptamine-induced secretion by rat jejunum in-vitro involves several 5-hydroxytryptamine receptor subtypes.

The receptors contributing to 5-hydroxytryptamine (5-HT)-induced anion secretion by rat jejunum have been investigated by testing the effects of selective agonists and antagonists in-vitro using both intact and stripped intestinal sheets. In both intact and stripped jejunum 5-HT and 5-methoxytryptamine, an agonist that lacks affinity for 5-HT3 receptors, induced concentration-dependent increases in the short-circuit current (SCC), although 5-methoxytryptamine induced a smaller maximum response. In intact sheets 1-phenylbiguanide, a selective 5-HT3 agonist, induced a response that was similar in magnitude to that of 5-methoxytryptamine, but in stripped preparations it had little effect. Tetrodotoxin inhibited the response of intact jejunum to 5-HT (by 86%) and 5-methoxytryptamine (by 85%) and abolished the response to 1-phenylbiguanide. In stripped sheets inhibition of the 5-HT response by tetrodotoxin was reduced to 27%. Desensitization to 1-phenylbiguanide reduced the response to 5-HT in intact but not stripped sheets whereas, in contrast, desensitization to 5-methoxytryptamine inhibited the 5-HT response in stripped sheets but was without effect in intact sheets. Mianserin, a 5-HT1, 5-HT2 and 5-HT3 antagonist, and renzapride, a 5-HT1 and 5-HT3 antagonist, both reduced the maximum response to 5-HT, but 5-HTP-DP, a 5-HT1 antagonist, was without effect. The 5-HT3 antagonist granisetron reduced the response to 5-HT in intact, but not in stripped sheets. Tropisetron, a 5-HT3 and 5-HT4 antagonist, inhibited the response to 5-methoxytryptamine in both preparations, but did not alter the response to 5-HT. It is concluded that 5-HT-induced jejunal secretion involves more than one 5-HT receptor subtype, with both neural and non-neural mechanisms contributing to the response.

Several receptor subtypes contribute to 5-hydroxytryptamine-induced secretion by rat ileum in-vitro.

The receptors contributing to 5-hydroxytryptamine (5-HT)-induced secretion by rat ileum were investigated in-vitro using selective agonists and antagonists. 5-HT induced a dose-dependent increase in the short-circuit current (SCC) generated by both intact and stripped sheets of rat ileum. 1-Phenylbiguanide, a selective 5-HT3 agonist, and 5-methoxytryptamine, an agonist that lacks affinity for 5-HT3 receptors, also increased the SCC. In intact sheets 5-HT was more effective than either 1-phenylbiguanide or 5-methoxytryptamine, whereas in stripped sheets 5-HT and 5-methoxytryptamine were equipotent, with 1-phenylbiguanide having little effect. Tetrodotoxin abolished the response of intact sheets to 1-phenylbiguanide but only reduced the responses to 5-HT and 5-methoxytryptamine by 57% and 54%, respectively. This inhibition was reduced to 25% in stripped sheets. The 5-HT3 antagonist granisetron abolished the response to 1-phenylbiguanide, but did not alter the effects of 5-HT. Ketanserin, a 5-HT2 antagonist, had a small effect on the actions of 5-methoxytryptamine in intact, but not stripped, sheets and no effect on the response to 5-HT in either preparation. Tropisetron, a 5-HT3 and 5-HT4 antagonist, inhibited the response to 5-methoxytryptamine, but had less effect on the response to 5-HT. Desensitization to 1-phenylbiguanide inhibited the response to 5-HT in intact, but not stripped sheets, whereas desensitization to 5-methoxytryptamine abolished the 5-HT response in stripped sheets, but induced only 42% inhibition in intact sheets. Previous exposure to a combination of both 1-phenylbiguanide and 5-methoxytryptamine abolished the 5-HT-induced increase in SCC in both preparations. The findings suggest that 5-HT-induced ileal secretion involves more than one 5-HT receptor subtype and that both neural and non-neural mechanisms contribute to the response.

Comparison of the intestinal secretory response to 5-hydroxytryptamine in the rat jejunum and ileum in-vitro.

A secretory response to 5-hydroxytryptamine (5-HT) is observed throughout the intestinal tract; this investigation has compared the nature of this response in the jejunum and ileum of the rat in-vitro. Different basal electrical activity was observed for jejunal and ileal sheets of rat small intestine. In both intact and stripped preparations the basal short-circuit current (SCC) was greater and the tissue resistance lower in the jejunum than in the ileum. 5-HT caused concentration-dependent increases in SCC in intact and stripped preparations of both regions. EC50 values were similar in the jejunum and ileum, stripped sheets from both regions showing greater sensitivity. In the ileum the maximum increase in SCC induced by 5-HT was similar in intact and stripped sheets, but in the jejunum the response was greater in intact preparations. The jejunal response to 5-HT was reduced in the absence of bicarbonate but unaffected by lack of chloride, whereas the ileal response was inhibited by removal of chloride but unaltered in bicarbonate-free conditions. In intact sheets the tetrodotoxin-sensitive neural component was greater in the jejunum. In stripped sheets a neural component could still be detected in the ileum, but not in the jejunum. There are, therefore, fundamental differences in the way in which the jejunum and ileum respond to 5-HT stimulation--the jejunal response is primarily a result of stimulation of bicarbonate secretion whereas chloride secretion predominates in the ileum. The myenteric plexus appears to play a more prominent role in the jejunum; in the ileum other neural elements also contribute to the response.

Chloride conductance and sodium-dependent glucose transport in rat and human enterocytes.

BACKGROUND & AIMS: In cystic fibrosis intestine, there is an increase in the rate of Na+-dependent glucose absorption. This may result from enterocyte hyperpolarization after defective Cl- channel function, but only if Cl- secretion and Na+/glucose cotransport occur in the same membrane. This study examined the effects of Cl- gradients on Na+/glucose uptake in brush border membrane vesicles from rat and human small intestine. METHODS: Vesicles were prepared by Mg2+-precipitation, and the active uptake of tritiated glucose was measured using a filtration-stop protocol. RESULTS: An outwardly directed Cl- gradient inhibited active glucose uptake in rat vesicles, whereas an inward Cl- gradient stimulated uptake. These effects were sensitive to blockers of the cystic fibrosis transmembrane regulator but not to inhibitors of other Cl- channels. Active glucose uptake into vesicles prepared from normal human intestine was also inhibited by an outward Cl- gradient, whereas uptake into vesicles prepared from a single sample of human cystic fibrosis intestine was not. CONCLUSIONS: A Cl- conductance resembling the cystic fibrosis transmembrane regulator is colocalized with Na+/glucose cotransport in rat and human small intestine, supporting the possibility that abnormalities in glucose absorption in cystic fibrosis may be a secondary effect of defects in Cl- channel function.

Thoracolumbar disc degeneration in young fast bowlers in cricket: a follow-up study.

OBJECTIVE: To determine the progression of thoracolumbar disc degeneration in young fast bowlers in cricket. DESIGN: Prospective fast bowling technique and MRI follow-up study. BACKGROUND: Previous studies on high-performance young fast bowlers have found that lumbar spine pathology was related to the mixed bowling technique. METHODS: Nineteen young male fast bowlers (mean age 13.6 years) underwent MRI scans to detect the presence of intervertebral disc abnormalities. Subjects were also filmed laterally (200 Hz) and from directly above (100 Hz) whilst bowling two maximum velocity deliveries (session 1). Subjects were tested using an identical methodology 2.7 years later (session 2). RESULTS: At session 1, the incidence of thoracolumbar disc degeneration was 21%; however, at session 2, the incidence significantly (P = 0.008) increased to 58%. Furthermore the increase in the incidence of back pain between session 1 and session 2 was also significant (P = 0.002). The progression of disc degeneration was found to be significantly (P = 0.015) related to the group of fast bowlers who utilized the mixed technique during both session 1 and 2 when compared to those who used this technique during one session only. CONCLUSIONS: Thoracolumbar disc degeneration and back pain increase significantly during the time period examined in this study. Further, bowlers who utilize the mixed bowling technique stand a greater chance of developing degenerative changes of the spine.

Influence of peppermint oil on absorptive and secretory processes in rat small intestine.

BACKGROUND: Peppermint oil is used to relieve the symptoms of irritable bowel syndrome, relaxing intestinal smooth muscle by reducing the availability of calcium, but its effects on intestinal transport are unknown. AIMS: To determine the effect of peppermint oil on intestinal transport processes. METHODS: The influence of peppermint oil on intestinal transport was investigated in rat jejunum using both intestinal sheets mounted in Ussing chambers and brush border membrane vesicles. RESULTS: Mucosal peppermint oil (1 and 5 mg/ml) had no significant effect on basal short circuit current, but inhibited the increase associated with sodium dependent glucose absorption. The increased short circuit current induced by serosal acetylcholine, a reflection of calcium mediated electrogenic chloride secretion, was unaffected by mucosal peppermint oil (5 mg/ml). In contrast, serosal peppermint oil (1 mg/ml) inhibited the response to acetylcholine without reducing the effect of mucosal glucose. In brush border membrane vesicles active glucose uptake was inhibited by extravesicular peppermint oil at concentrations of 0.5 and 1 mg/ml. CONCLUSIONS: Peppermint oil in the intestinal lumen inhibits enterocyte glucose uptake via a direct action at the brush border membrane. Inhibition of secretion by serosal peppermint oil is consistent with a reduced availability of calcium.