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Biomedical subjects

D Parekh

Publications and source records attributed to D Parekh.

At least 37 records · Page 2Linked to original sources
PubMed1994

Laparoscopic cholecystectomy: laboratory predictors of choledocholithiasis.

Liver function tests (LFTs) are most often employed to select patients for preoperative endoscopic retrograde cholangiography (ERC) and therapeutic sphincterotomy. Although ERC accurately detects CBD stones, the associated financial costs and potential morbidity argue against its indiscriminate use. We analyzed the value of LFTs to predict CBD stones in patients treated by laparoscopic cholecystectomy (LC). CBD stones were identified in 41 of 660 patients (6.2%) treated by LC during the study period (January 1991 to May 1993). CBD stones were identified by preoperative ERC in 19 of 33 patients (57.6%); by operative cholangiography in 18 of 289 patients (6.2%), and by postoperative ERC in 4 patients. In patients with CBD stones, there was a significant difference in alkaline phosphatase, total bilirubin, SGPT, and SGOT (P < 0.001). The positive predictive value (PPV) of a value > normal at admission was 5%-19%; and immediately before operation was 9%-36%. The PPV of a value > 2X normal was 30%-47%. Alkaline phosphatase and total bilirubin were independent predictors of CBD stones. If both were greater than twice normal, there was a 55 per cent incidence of CBD stones. Our analysis suggests that patients with greater than twice normal liver function tests have a sufficient incidence of CBD stones to warrant ERC. Patients without both these criteria should be managed by laparoscopic CBDE, with postoperative endoscopic stone retrieval for the failures of laparoscopic CBDE.

Adult↗
PubMed1993

Effects of aging on gastrin and somatostatin secretion from isolated perfused rat stomach.

We have examined the release of gastrin and somatostatin from the isolated perfused stomach of rats of three different age groups (4 months, 12 months, and 24 months old) in response to bombesin and carbachol. The basal release of gastrin was diminished in 24-month-old rats. Basal somatostatin release showed an age-related decrease. Bombesin (10(-10) and 10(-9) M) and carbachol (10(-8) and 10(-7) M) stimulated gastrin release in each age group. The integrated release of gastrin in response to bombesin (10(-10) and 10(-9) M) or carbachol (10(-8) M) did not differ among the three age groups, although integrated gastrin release in response to carbachol (10(-7) M) decreased in 24-month-old rats. Bombesin-stimulated release of somatostatin decreased in 12- and 24-month-old rats. Carbachol inhibited release of somatostatin in each age group. Compared with 4-month-old rats, the inhibition of somatostatin release by carbachol was less in 24-month-old rats at 10(-8) and 10(-7) M, and less in 12-month-old rats at 10(-7) M. The decreased basal gastrin secretion and well-preserved gastrin response were further confirmed in conscious aged rats tested by means of oral gavage with 10% peptone. Our findings indicate that gastrin response to the stimuli is well preserved with aging, whereas the response of somatostatin diminishes in an age-related manner. Aging has different effects on the release of gastrin and somatostatin from the rat stomach.

Aging↗
PubMed1993

Bombesin stimulates growth of colon cancer in mice and decreases their survival.

Bombesin (BBS) stimulates cellular proliferation of both normal and transformed cells. The mouse colon cancer cells (MC-26) possess specific binding sites for BBS. The purpose of this study, therefore, was to examine the effect of chronic administration of BBS on in vivo growth of MC-26 tumours in Balb/c mice and on survival of tumour-bearing mice. Three groups of mice (n = 10 each) inoculated with MC-26 cells received either saline containing 0.1% bovine serum albumin (BSA), or BBS (5 micrograms kg-1 or 20 micrograms kg-1) dissolved with 0.1% BSA saline by intraperitoneal route three times a day for 15 days. BBS increased weight, DNA and RNA contents of MC-26 tumours. To examine the effect of BBS on survival rates of mice with MC-26 tumours, three groups of mice (n = 20 each) were treated for 31 days, as above. One group of mice inoculated with MC-26 cells received 0.1% BSA saline; the other group of MC-26-inoculated mice and the control group without tumour received BBS (5 micrograms kg-1) dissolved with 0.1% BSA saline. BBS significantly decreased the survival rate of mice bearing MC-26 tumours (median survival; saline group: 42.5 days, BBS group: 32.0 days, P = 0.037). None of the mice in the control group died during the experiment. BBS may stimulate in vivo growth of MC-26 cells through specific receptors.

Animals↗
PubMed1993

The effect of endogenous cholecystokinin released by bombesin and trypsin inhibitor on the regeneration of the pancreas.

OBJECTIVE: This study examined the effects of endogenous cholecystokinin (CCK) released by bombesin and FOY-305 (a synthetic inhibitor of trypsin on pancreatic regeneration in rats). SUMMARY BACKGROUND DATA: Trophic gut hormones (CCK and bombesin) stimulate the growth of the normal rat pancreas. However, the influence of endogenous gut hormones on pancreatic regeneration is unclear. METHODS: Male Fisher rats (n = 6 to 8 per group) were fed a protein-free diet and given ethionine (700 mg/kg intraperitoneally daily) for 8 to 9 days to induce degeneration of the pancreas. Regeneration was stimulated by giving the rats a regular chow diet. The effects of bombesin (10 micrograms/kg three times a day for 7 days) or FOY-305 (200 mg/kg daily for 8 days) on the process of regeneration were examined. RESULTS: At the end of the degeneration phase, there was near-total destruction of pancreatic acinar cells. Both bombesin and FOY-305 stimulated pancreatic regeneration. Growth measurements (weight and total content of DNA and protein) were significantly increased (p < 0.05) in the bombesin- and FOY-305-treated rats compared with controls. Histologic examination revealed widespread repopulation of the pancreas with acinar cells in the bombesin- and FOY-305-treated groups. The stimulating effects of both bombesin and FOY-305 on pancreatic regeneration were blocked completely by the CCK-receptor antagonist L-364,718. Growth measurements were not significantly increased in the groups of control rats or rats given L-364,718 alone. CONCLUSIONS: These results show that bombesin and FOY-305 significantly stimulated pancreatic regeneration. Because the stimulating effects of bombesin and FOY-305 on regeneration were blocked by the specific CCK-receptor antagonist L-364,718, it was concluded that this effect was mediated by endogenous CCK.

Animals↗
PubMed1993

Treatment of pancreatic ascites and external pancreatic fistulas with a long-acting somatostatin analogue (Sandostatin).

Prior to the advent of somatostatin conservative therapy for pancreatic fistulas, treatment included intravenous nutritional therapy with nothing per mouth and therapeutic agents to diminish pancreatic secretions. None of these modalities were uniformly successful. A prospective study to evaluate the efficacy of a long-acting somatostatin analogue (Sandostatin) was carried out. 18 patients-10 with pancreatic ascites and 8 with external pancreatic fistulas-were treated. The ascites resolved in 9 of 10 patients in a mean period of 22 days (+/- 3 days). The external fistulas were all high output fistulas and resolved in 7 of 8 patients. Mean period for closure was 23 days. There were no side effects associated with Sandostatin. Sandostatin has made a major impact on the conservative treatment of pancreatic ascites and is an important adjunct to the management of external pancreatic fistulas. It is emphasised however that surgery may be required for the underlying pancreatic disease. In this regard close surveillance of these patients is necessary.

Adult↗
PubMed1993

The role of total enteral nutrition in pancreatic disease.

Conflicting data have been reported on the use of total enteral nutrition (TEN) in pancreatic disease. TEN was used in 17 patients who were candidates for nutritional support with total parenteral nutrition (TPN). There were 7 patients with internal pancreatic fistulas, 2 with protracted traumatic pancreatitis, 7 with severe alcoholic pancreatitis and 1 with a traumatic pancreatic pseudocyst. The mean inhospital stay was 30 days. Precision LR was administered orally or nasally for a mean of 16 days. Five patients with internal pancreatic fistulas were healed during the initial admission on TEN, 1 required surgery and 1 defaulted from hospital treatment. Nine patients with pancreatitis improved on TEN with resolution of pseudocysts or phlegmons (8 patients); 1 patient required a cystojejunostomy. Three patients who defaulted on TEN and consumed a ward diet had relapse of the pancreatitis, which responded rapidly to re-institution of hyperalimentation. There was no mortality in this group of patients. This preliminary report suggests that TEN may be considered as an alternative to TPN for nutritional support in pancreatic disease.

Adult↗
PubMed1992

Choledochoduodenal fistula from a penetrating duodenal ulcer. A case report.

Choledochoduodenal fistula is an uncommon complication of duodenal ulcer disease. The role of medical therapy is unclear and surgical management has been recommended for the condition. A patient who was treated with ranitidine 150 mg twice daily for 8 weeks for a giant duodenal ulcer with a choledochoduodenal fistula is reported. Both the ulcer and the fistula completely healed on medical therapy. Medical therapy may now become the treatment of choice for this condition due to the availability of potent acid-reducing agents.

Adult↗
PubMed1992

Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide.

The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality.

Ascites↗
PubMed1992

Gastric acid secretion and gastrin release in the baboon.

Significant species differences have been demonstrated in gastric physiology, a factor that limits extrapolation of animal data to man. Primate physiology is thought to be similar to that of man; however, gastric function has not been adequately documented in the primate. In the present study six baboons (body weight 25.5 +/- 1.8 kg) were trained to sit in a chair and gastric acid secretion and gastrin release was studied in conscious animals. Mean basal acid secretion was 1.3 +/- 0.1 mmol (H+)/hr. Maximum output after pentagastrin (12 micrograms/kg/hr) was 9.5 +/- 0.9 mmol (H+)/hr and 11.0 +/- 0.4 mmol (H+)/hr after histamine (40 micrograms/kg/hr). A statistically significant (by cosinor analysis) circadian rhythm was demonstrated for intragastric pH over 24 hr in fasted baboons (P less than 0.001). Mean basal serum gastrin level was 37.7 +/- 8.3 pg/ml. The integrated gastrin response after administration of a protein rich meal was 2.52 +/- 0.07 ng x min/ml and this increased to 5.17 +/- 0.18 ng x min/ml (P less than 0.05) following simultaneous administration of a meal with atropine (0.2 mg/kg) (P less than 0.05). Our results suggest that there is significant basal and stimulated acid secretion in the baboon; the amount of acid secreted is similar to that reported in man. Gastric pH demonstrated a circadian rhythm. Postprandial gastrin release was significantly enhanced by cotreatment with atropine. As the present findings are similar to those previously reported in man, the baboon may be a useful model for further studies in gastric physiology and experimental peptic ulceration.

Animals↗
PubMed1992

Neurotensin stimulates growth of colonic mucosa in young and aged rats.

Neurotensin, a tridecapeptide widely distributed in the gut, stimulates growth of small bowel mucosa in young and aged rats. In the present study, the effect of long-term neurotensin administration on the growth of colonic mucosa was examined in young (2-month-old) and aged (24-month-old) rats. Subcutaneous injections of saline (control) or neurotensin (300 micrograms/kg) in gelatin were given to the groups of rats every 8 hours for 10 days. During treatment, all rats were maintained on a regular chow diet. Rats were killed on day 11; the entire colon was removed, mucosa was scraped and weighed, and DNA, RNA, and protein contents were determined. Neurotensin induced growth of colonic mucosa in both age groups. In young rats, neurotensin increased weight and DNA, RNA, and protein contents of colonic mucosa. The ratio of DNA content, an index of cellular hyperplasia, was increased significantly in the neurotensin-treated young rats compared with age-matched controls, indicating an overall increase in mucosal cellularity. In the aged rats, growth was characterized by an increase in weight and RNA and protein contents, but not DNA content, thus suggesting cellular hypertrophy. These results suggest that neurotensin has an important regulatory function in the growth of colonic mucosa; however, the mode of action, at the cellular level, appears to be different depending on age.

Aging↗
PubMed1992

Neurotensin stimulates growth of colon cancer.

Neurotensin (NT), a peptide from the distal gut that is released by fat ingestion, stimulates the growth of normal small bowel and colonic mucosa. The purpose of this study was to determine whether chronic administration of NT would affect the growth of a mouse colon cancer (MC-26) and a human colon cancer (LoVo) in vivo. In experiment 1, male Balb/c mice were inoculated with MC-26 cells (5 x 10(4)) and then randomized to four treatment groups receiving either saline (control) or NT (150, 300 or 600 micrograms kg-1) administered subcutaneously (s.c.) every 8 h for 21 days. In experiment 2, 60 mice with MC-26 tumours were randomized to receive saline (control) or NT (300 or 600 micrograms kg-1) for 28 days, and survival was then assessed. In experiment 3, 16 athymic nude mice with LoVo tumour xenografts were randomized to receive either saline (control) or NT (600 micrograms kg-1). We found that administration of NT (300 and 600 micrograms kg-1) significantly stimulated mean tumour area, weight and DNA, RNA and protein content of MC-26 tumours. In addition, the survival rate of mice bearing MC-26 tumours and treated with either dose of NT was significantly decreased compared with the control group given saline injections. Similarly, NT (600 micrograms kg-1) stimulated growth (tumour area, weight and nucleic acid contents) of the human colon cancer, LoVo. We conclude that NT acts as a tropic factor for the colon cancer cell lines MC-26 and LoVo in vivo. NT may play an important role in growth regulation of certain colon cancers.

Analysis of Variance↗
PubMed1992

Amiloride inhibits the growth of human colon cancer cells in vitro.

Cytoplasmic alkalinization induced by activation of the Na+/H+ antiport plays an essential role in the initiation of cell proliferation. In the present study we examined the effects of amiloride, a specific and reversible inhibitor of Na+/H+ antiporter, on the growth of human colon cancer cells (HT-29). Amiloride (50-800 microM) inhibited the growth of HT-29 cells in a dose-dependent fashion. Forty-three percent inhibition of growth was found at an amiloride concentration of 400 microM after 4 days of treatment. The inhibitory effect of amiloride on growth of HT-29 cells was reversible since removal of amiloride by a media change after 48 h treatment lead to rapid regrowth to control levels. The reversibility of growth inhibition suggests that amiloride is not a non-specific cytotoxin for HT-29 cells. We examined the possible mechanisms for the inhibitory effects of amiloride. Amiloride (400 microM) completely abolished serum-stimulated ODC activity and inhibited difluoromethylornithine (DMFO)-stimulated putrescine uptake by 56%. We conclude that amiloride inhibits the in vitro growth of human colon cancer cells; since ODC-activity and polyamine transport were both inhibited, the inhibitory effects may be mediated in part by polyamine-dependent processes. Amiloride may be a useful agent in the treatment of colon cancer.

Adenocarcinoma↗
PubMed1992

Sodium butyrate stimulates polyamine biosynthesis in colon cancer cells.

Differentiation inducers act through polyamine-dependent and independent pathways. Sodium butyrate (NaB) inhibits proliferation and induces terminal differentiation in human and murine cancer cell lines. An effect of this agent on polyamine biosynthesis has not been demonstrated previously. In the present study, we examined the effects of NaB on polyamine biosynthesis in mouse colon cancer (MC-26) cells. All studies were performed on exponentially growing cells, and ODC and polyamine transport measurements were performed as described previously. NaB inhibited the growth of MC-26 cells in a dose-dependent manner. Cell shape was significantly altered by treatment with NaB (development of dendritic-like processes and flattening and spreading out of cells on culture dishes). NaB stimulated ODC activity in a dose-dependent manner. The activity was elevated by 8 h after treatment, and at 48 h there was a ten-fold increase in activity (compared with control activity). The increase in ODC activity led to an increase in polyamine biosynthesis; putrescine, spermidine, and spermine levels in MC-26 cells were significantly elevated by 24 h after treatment with NaB. Polyamine uptake was similar in control cells and cells treated with NaB alone. Our finding of significant stimulation of polyamine uptake by NaB after inhibition of endogenous synthesis (by an ODC-dependent pathway) in DFMO-treated cells suggests that cellular requirements are increased for polyamines in NaB-treated cells. We conclude that polyamine-dependent processes are important in the mechanism of action of NaB in colon cancer cells.

Animals↗
PubMed1992

Neurotensin augments intestinal regeneration after small bowel resection in rats.

Massive small bowel resection (SBR) is characterized by increased proliferation of residual gut mucosa and pancreas. Neurotensin (NT), a gut tridecapeptide, stimulates growth of normal gut mucosa and pancreas. This study examined whether NT affected growth of the small intestine and the pancreas after either distal or proximal SBR. Male Fischer 344 rats were divided into four groups. Group 1 underwent ileal transection with reanastomosis (SHAM) and group 2 underwent 70% distal SBR. Group 3 underwent SHAM operation (jejunal transection), and group 4 underwent 70% proximal SBR. After operation, each group was further subdivided to receive either saline (control) or NT (300 micrograms/kg) subcutaneously in gelatin every 8 hours for 7 days. At death, the pancreas and proximal jejunum (from groups 1 and 2) or distal ileum (from groups 3 and 4) were removed, weighed, and analyzed for DNA, RNA, and protein content. Both proximal and distal SBR significantly increased mucosal growth in the remnant intestine; a more pronounced effect was noted with proximal SBR. Administration of NT significantly augmented the adaptive changes in both groups of rats by mechanisms involving increases in both cell size (hypertrophy) and cell number (hyperplasia). Pancreatic growth was stimulated by distal (but not proximal) SBR; NT did not augment this response. The authors conclude that NT augments intestinal growth after SBR by mechanisms involving an increase in overall mucosal cellularity. Administration of NT may be therapeutically useful to enhance mucosal regeneration during the early period of adaptive hyperplasia after SBR.

Animals↗
PubMed1991

Differential effects of sodium butyrate and hexamethylene bisacetamide on growth and secretion of cultured human endocrine tumor cells.

Advanced gastrointestinal endocrine tumors respond poorly to conventional chemotherapy. In this study we examined the effects of two agents that promote cellular differentiation, sodium butyrate and hexamethylene bisacetamide, on the in vitro growth and secretory responses of a human pancreatic carcinoid (BON) and human gastrinoma (PT-2 and PT-SM) cell lines that have been established in our laboratory. We found that both sodium butyrate and hexamethylene bisacetamide strongly inhibited growth of BON, PT-2, and PT-SM cells. With continuous exposure of BON cells to sodium butyrate (2 mmol/L), the doubling time was prolonged, from 60 hours in controls to 156 hours, and saturation density was reduced to 28% that of controls. Hexamethylene bisacetamide (4 mmol/L) reduced saturation density to 37% that of controls in BON cells and prolonged the doubling time, from 60 hours to 103 hours. Antiproliferative effects of similar magnitudes were observed in the gastrinoma cell lines. In contrast, differential effects were produced on amine biosynthesis in BON cells; sodium butyrate stimulated levels of 5-hydroxytryptamine in the cells, whereas hexamethylene bisacetamide caused a profound dose-dependent inhibition of amine biosynthesis. The significant antiproliferative activity of sodium butyrate and hexamethylene bisacetamide and the inhibitory effects of hexamethylene bisacetamide on amine biosynthesis warrant evaluation of these agents or analogues for treatment of metastatic carcinoid and gastrinoma.

5-Hydroxytryptophan↗
PubMed1991

Pancreatic regeneration after partial pancreatectomy.

The ability of the pancreas to regenerate and the effects of trophic hormones on regeneration of the pancreas after partial pancreatectomy are not completely understood. We investigated the effects of the trypsin inhibitor FOY-305 (an agent that stimulates endogenous cholecystokinin) on pancreatic regeneration after partial pancreatectomy in rats. FOY-305 or water was administered for either 13 days or 27 days by gavage feeding, after sham operation or partial pancreatectomy (n = 6 to 8 animals per group). FOY-305 stimulated hypertrophy of the pancreatic remnant at 13 days; prolonged treatment for 27 days produced both hypertrophy and hyperplasia. The magnitude of pancreatic growth after FOY-305 administration was significantly greater at 27 days in the pancreatic remnant than growth of the equivalent pancreatic segment (duodenal and parabiliary) in sham-operated rats treated with FOY-305. Our results suggest that endogenous cholecystokinin released by FOY-305 stimulates regeneration after partial pancreatectomy. The pancreatic remnant is more sensitive to trophic stimulation in comparison to the normal pancreas. FOY-305 may be a useful agent in the treatment of pancreatic insufficiency after extensive subtotal pancreatectomy or chronic pancreatitis.

Animals↗
PubMed1991

Somatostatin and analogues in the treatment of cancer. A review.

Somatostatin is a naturally occurring cyclic tetradecapeptide that inhibits release of growth hormone and all gastrointestinal hormones. The beneficial effect of somatostatin in the treatment of certain hypersecretory disorders of hormone excess in well recognized; however its clinical usefulness has been limited in the past by its extremely short plasma half-life. The development of long-acting somatostatin analogues has provided clinically useful agents for treatment of hormone-producing tumors. In addition to well-known inhibiting effects on hormone release and actions, recent studies using experimental tumor models have demonstrated an antiproliferative effect of somatostatin and its analogues on growth of a variety of neoplasms. The exact role of somatostatin analogues in cancer therapy has yet to be established; however studies suggest that these agents could provide a useful and relatively nontoxic adjuvant therapy in the treatment of certain tumors. In this review, the oncologic application of somatostatin and possible mechanism of action are examined and current clinical and experimental studies are summarized.

Breast Neoplasms↗