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Biomedical subjects

J M Howard

Publications and source records attributed to J M Howard.

At least 19 recordsLinked to original sources
PubMed2001

Optical design using computer graphics.

For decades the computer has been the primary tool used for optical design. Typical tasks include performing numerical calculations for ray tracing and analysis and rendering graphics for system drawings. As machines become faster with each new generation, the time needed for a particular design task has greatly reduced, allowing multiple assignments to be performed with little noticeable delay. This lets the designer modify a system and then immediately see the results rendered in graphics with a single motion. Such visual design methods are discussed here, where graphics of systems and plots relating to their performance are produced in real time, permitting the optical designer to design by pictures. Three examples are given: an educational tutorial for designing a simple microscope objective, an unobstructed reflective telescope composed of three spherical mirrors, and a modified Offner relay with an accessible pupil.

Journal Article↗
PubMed2001

Invasiveness and MMP expression in pancreatic carcinoma.

BACKGROUND: Previous investigations have suggested that expression of matrix metalloproteinases (MMPs) may be related to increased invasiveness of various tumors. This study evaluated a possible relation between pancreatic tumor cell invasiveness and MMPs. METHODS: A Matrigel invasion assay was performed with pancreatic tumor cell line SUIT-2 and its sublines S2-007, S2-013, S2-020, and S2-028. The degree of invasiveness of stimulated and unstimulated cell lines was correlated with MMP gene expression measured by RT-PCR and MMP protein product measured by gelatin zymography. Cell lines were stimulated by 12-O-tetradecanoylphorbol-13-acetate (TPA), concanavalin (Con-A), and polymerized collagen type I gel (Vitrogen). RESULTS: For SUIT-2, S2-007, S2-013, S2-020, and S2-028, 3.2, 1.0, 4.1, 6.4, and 0.4%, respectively, of the cells invaded the Matrigel membrane. TPA, Con-A, and Vitrogen resulted in the up-regulation of MMP-2 in S2-020. TPA and Vitrogen resulted in up-regulation of MMP-9 in each of the cell lines, while Con-A could up-regulate MMP-9 expression only in SUIT-2. There was no constitutive expression of either MMP-2 or MMP-9 in SUIT-2 or its sublines. There was a positive relationship between Matrigel invasiveness and up-regulation of MMP-2 and MMP-9 expression. CONCLUSION: These data suggest that, while MMP-2 and MMP-9 are not constitutively expressed in pancreatic carcinoma cell lines, they may be up-regulated by TPA, Con-A, and Vitrogen. Since MMP-2 and MMP-9 expression correlated with degree of tumor cell invasiveness, the ability to up-regulate MMP-2 and MMP-9 expression may play a role in facilitating pancreatic tumor cell invasion.

Biocompatible Materials↗
PubMed2001

Mechanisms of taxotere-related drug resistance in pancreatic carcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAC) is generally refractory to most chemotherapeutic agents, including docetaxel (Taxotere; TXT). Specific mechanisms for TXT-related drug resistance in PAC have not been defined. The hypothesis of this study was that PAC resistance to TXT is primarily related to P-glycoprotein (P-gp), the expression product of multiple drug resistance (MDR)-1, as opposed to lung resistance protein (LRP) or multidrug resistance protein (MRP). MATERIALS AND METHODS: The sensitivity of the PAC cell line SUIT-2 and its sublines to TXT, doxorubicin (DOX) and 5-fluorouracil (5-FU) was evaluated with a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. MDR1 (P-gp), MRP, LRP, and beta-tubulin isotype gene expressions were detected at the messenger RNA level by reverse transcription-polymerase chain reaction (RT-PCR). Verapamil and indomethacin (IMC) were used to test the functionality of P-gp and MRP, respectively. RESULTS: The SUIT-2 subline S-020 and the TXT-selected SUIT-2 cell line S2/TXT were significantly resistant to TXT. Both showed cross-resistance to DOX but no resistance to 5-FU. RT-PCR demonstrated strong expression of P-gp in S-020 and S2/TXT and weaker or no expression in other cells lines. MRP and LRP expression was found in most of these cell lines but had no relationship to the TXT resistance. TXT resistance in S2-020 and S2/TXT could be reversed by verapamil but not by IMC. Levels of beta-tubulin isotype II and III were increased in S2/TXT compared with S-020 and SUIT-2. CONCLUSIONS: Intrinsic and acquired TXT resistance is primarily mediated by P-gp, but not by MRP or LRP, and is markedly reversed by the P-gp modulator verapamil. Hence future related studies should focus on the use of agents that block the transporter action of P-gp.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

Isotretinoin-induced inflammatory bowel disease in an adolescent.

OBJECTIVE: To report a case of inflammatory bowel disease (IBD) associated with use of isotretinoin. CASE SUMMARY: 17-year-old boy presented with new-onset rectal bleeding after completion of a five-month course of isotretinoin. A diagnosis of ulcerative colitis was made. His condition worsened despite therapy with 5-aminosalicylic acid, steroid retention enema, iron supplement, and prednisone. Five months after the onset of rectal bleeding, he had lost 11.4 kgand developed bilateral pitting edema of the hips and profound anemia. A subtotal colectomy and ileostomy was performed. DISCUSSION: Rectal bleeding has been reported to occur during or up to several years after treatment with isotretinoin. The mechanism by which isotretinoin may induce IBD is unknown. Proposed mechanisms include inhibition of epithelial cell growth resulting in ulceration and inflammation of the gut mucosa, inhibition of glycoprotein synthesis affecting the integrity of the mucosal wall, and stimulation of kiler T cells, leading to epithelial cell injury and a resultant inflammatory response. CONCLUSION: This case of probable isotretinoin-induced IBD suggests that patients with suspected IBD should be asked about current or past use of isotretinoin to improve documentation of this serious adverse event.

Acne Vulgaris↗
PubMed2000

Flow limitation in infants assessed by negative expiratory pressure.

Forced expiratory flows by the rapid compression technique are often used to assess airway function in infants; however, it remains unclear as to whether flow limitation (FL) is achieved. Studies in adults have used negative expiratory pressure (NEP) at the airway opening as a noninvasive technique to assess whether FL is achieved. An increase in flow with NEP indicates that FL has not been achieved, whereas no increase in flow with NEP indicates FL has been achieved. In the adult studies, the change in flow was assessed by visual inspection of the flow-volume curve. We evaluated whether NEP could be used to assess FL during forced expiration in infants. In addition, we quantified the change in flow secondary to NEP. We applied -5 cm H(2)O NEP to four infants during forced expiratory maneuvers. The step increase in flow with NEP was always less than 5% at high jacket compression pressures and consistent with FL. For one subject, FL was also confirmed from isovolume pressure flow-curves measured with an esophageal catheter. We conclude that NEP can be used in infants to assess FL during forced expiratory maneuvers by the rapid compression technique.

Adult↗
PubMed1999

Development and progress in resective surgery for pancreatic cancer.

Pancreatoduodenectomy was developed from experience gained with transduodenal ampullectomy, preceded by a relatively bloodless cholecystoenterostomy. Although Codivilla (1898) and Kausch (1909) each achieved a single survivor following pancreatoduodenectomy, further development of the operation had to await discovery of vitamin K and a description of human blood types, the latter leading to the development of blood banks. After vitamin K and blood banks became available, Allen O. Whipple and his resident C.R. Mullins developed the two-stage pancreatoduodenectomy (1934-1935) and Whipple the one-stage procedure (1940). Although the mortality rate from pancreatoduodenectomy remained approximately 33% for more than 25 after Whipple's reports, concentration of resection in "centers of specialization" has now reduced mortality rates below 5%. Thus operative survival has been achieved, but long-term survival has not kept pace. Long-term data remain inadequate because they are usually expressed as Kaplan-Meier estimates and because of the nonuniformity of reporting (e.g., exclusion of postoperative deaths and palliative resections, intraoperative adjuvant therapies, and variations of operative techniques). Widely based Kaplan-Meier estimates of 5-year survival range from 12% to 15% after resection and more than 20% in selected categories. Total pancreatectomy has not improved short- or long-term survival rates. Extended lymphadenectomy and resection of peripancreatic soft tissues, as currently developed in several surgical clinics in Japan, suggest a higher incidence of complications but perhaps more long-term survivors. Interpretation of their data is currently subject to the same limitations noted above. As our surgical forebears needed vitamin K and blood banks to achieve postresection survival, we and our students need effective adjuvant therapy of micrometastases and better modalities for early diagnosis to improve long-term survival.

History, 19th Century↗
PubMed1999

Pseudomyxoma peritonei: Sudden cardiac death complicating post operative intraperitoneal treatment with 5-fluorouracil.

BACKGROUND: Pseudomyxoma peritonei, a tumor which spreads chiefly along peritoneal surfaces, has recently been treated by resection followed by intraperitoneal infusion of 5-fluorouracil (5-FU). Reports on the cardiotoxicity of this drug, given intravenously, indicate an incidence of 1.4-2.9%. Although several deaths have been reported following 5-FU therapy by continuous intravenous infusion, none has apparently been reported following bolus intravenous injection. METHOD: Radical resection of an extensive pseudomyxoma peritonei was performed. Following convalescence, intraperitoneal infusion of 5-FU was initiated in a daily dose of 20 mg/kg body weight (1,440 mg), planned for administration in multiple 5-day cycles. RESULTS: After three uneventful daily infusions of 5-FU, the patient suddenly died, apparently of a sudden cardiac event. Autopsy provided no explanation for his death. The coronary arteries were free of disease and no residual tumor was found. A review of the literature reveals no report of a cardiac death from 5-FU following its intraperitoneal administration. CONCLUSIONS: The fatality suggests the potential toxicity of 5- FU when administered intraperitoneally, a factor to be considered in decisions to use this drug intraperitoneally.

Adult↗
PubMed1998

A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment (ASTRONAUT) Study Group.

BACKGROUND: Suppressing acid secretion is thought o reduce the risk of ulcers associated with regular use of nonsteroidal antiinflammatory drugs (NSAIDs), but the best means of accomplishing this is uncertain. METHODS: We studied 541 patients who required continuous treatment with NSAIDs and who had ulcers or more than 10 erosions in either the stomach or duodenum. Patients were randomly assigned to double-blind treatment with omeprazole, 20 mg or 40 mg orally per day, or ranitidine, 150 mg orally twice a day, for four or eight weeks, depending on when treatment was successful (defined as the resolution of ulcer and the presence of fewer than five erosions in the stomach, and fewer than five erosions in the duodenum, and not more than mild dyspepsia). We randomly assigned 432 patients in whom treatment was successful to maintenance treatment with either 20 mg of omeprazole per day or 150 mg of ranitidine twice a day for six months. RESULTS: At eight weeks, treatment was successful in 80 percent (140 of 174) of the patients in the group given 20 mg of omeprazole per day, 79 percent (148 of 187) of those given 40 mg of omeprazole per day, and 63 percent (110 of 174) of those given ranitidine (P<0.001 for the comparison with 20 mg of omeprazole and P=0.001 for the comparison with 40 mg of omeprazole). The rates of healing of all types of lesions were higher with omeprazole than with ranitidine. During maintenance therapy, the estimated proportion of patients in remission at the end of six months was 72 percent in the omeprazole group and 59 percent in the ranitidine group. The rates of adverse events were similar between groups during both phases. Both medications were well tolerated. CONCLUSIONS: In patients with regular use of NSAIDs, omeprazole healed and prevented ulcers more effectively than did ranitidine.

Adult↗
PubMed1998

Johann Georg Wirsüng (1589-1643) and the pancreatic duct: the prosector of Padua, Italy.

Although his primacy was subsequently challenged by a student, it is now known that Johann Georg Wirsüng, the prosector of Padua, Italy, discovered the human pancreatic duct in 1642 during the dissection of an executed murderer. Instead of publishing his discovery, he engraved a drawing of the duct on a copper plate, from which he made seven or more imprints. The copies were sent to leading anatomists of Europe with the question, "Should I call it an artery or a vein? I never found blood in it ...." Three and a half centuries later, the copper plate remains well preserved and the authors, to the surprise of European surgeons and librarians, but with their aid, have traced six copies of the "ductus Wirsüngianus" imprints still in existence. This is the story of Wirsüng the man, his subsequent assassination, and finally the recognition that his finding had opened a new field of science.

Anatomy↗
PubMed1998

Dietary intake of cobalamin in elderly people who have abnormal serum cobalamin, methylmalonic acid and homocysteine levels.

OBJECTIVE: To determine if poor dietary intake can explain the cobalamin-related abnormalities often seen in the elderly. DESIGN: Prospective laboratory survey with a follow-up dietary assessment. SETTING: Social centers for the elderly and an outpatient clinic. SUBJECTS: Ninety-five free-living subjects >60y old with abnormal or suspicious findings in cobalamin-related tests and 78 subjects >60y old with normal results. INTERVENTIONS: Serum cobalamin, methylmalonic acid and homocysteine determinations to assess cobalamin status and a one year food-frequency questionnaire to assess cobalamin intake. RESULTS: Only three of the 173 subjects (1.7%), one of whom had normal cobalamin status, ingested <2 microg cobalamin/d, the Recommended Daily Allowance. Sixty-nine subjects (39.9%) ingested <6 microg/d, but they did not have more abnormal serum cobalamin or metabolite values than those ingesting >6 microg. Ordering all subjects by quintiles according to cobalamin intake revealed no significant trends or differences in any of the serum values either. Moreover, arranging subjects by results of tests of cobalamin status showed that the subjects with abnormal cobalamin status did not differ in cobalamin intake from those with normal cobalamin status, although they did differ in use of supplements. Finally, cobalamin intake, with or without supplements, did not correlate with serum cobalamin or metabolite levels. The absence of any association between cobalamin status and intake contrasts sharply with the significant correlation between folate intake and folate status (P = 0.0001). CONCLUSIONS: The high frequency of mildly abnormal cobalamin status in the elderly cannot be attributed to poor intake of cobalamin. Nondietary explanations, such as malabsorption and other phenomena, must always be sought to explain mild cobalamin deficiency in the elderly.

Aged↗
PubMed1998

Carcinoid tumors of the pancreas. Status report based on two cases and review of the world's literature.

CONCLUSION: The diagnosis of a pancreatic carcinoid should be based on the measurement of serotonin in serum or its demonstration in the tumor and/or by the measurement of its derivative (5-HIAA) in urine. Carcinoid of the pancreas is a rare but definite entity; usually having metastasized by the time of diagnosis. The term "serotonin-producing tumor of the pancreas" has been suggested as an alternative designation for "pancreatic carcinoid." BACKGROUND: The literature on carcinoid tumors of the pancreas is confusing because much of it preceded the development of the more specific immunological, chemical and staining techniques currently available. METHODS: 43 case reports were collected from the world's literature, based on a demonstrable pancreatic neuroendocrine tumor plus a positive finding of at least one of the following without another dominant hormone being demonstrated: elevation of 5-Hydroxytryptamine (5-HT) (serotonin) in the serum or detected in tumor tissue, and/or elevation of 5-Hydroxyindole acetic acid (5-HIAA) in the urine. In addition to these two hormone-specific assays, information was collected on the silver-staining properties of the tumor; properties which have traditionally been associated with carcinoid tumors. Positive silver staining in tumor cells (argyrophilic and/or argentaffin reaction) is strongly indicative of the carcinoid tumor but the findings are less specific than the hormone assays and immunohistologic stains. RESULTS: In this review of 43 cases, including two current ones, the pancreatic carcinoid tumor has the following important features: 1. It is a rare tumor that is usually diagnosed late when the tumor is large and has metastasized. Thirty-eight (88.4%) have been malignant. They are, therefore, associated with a high incidence of the "carcinoid syndrome." 2. To date, prognosis in therapy is poor, based on delayed diagnosis, a resultant low incidence of resectability, and an uncertain duration of survival after resection. 3. Pancreatic carcinoid tumors remain difficult to differentiate from other endocrine tumors. The measurement of urinary 5-HIAA excretion or the demonstration of elevated serotonin level in the tumor or in serum is essential to its distinction. Silver staining of the tumor, although of historic importance, has been superceded by the hormone-specific studies. 4. To distinguish it from other endocrine tumors of the pancreas, the terms "pancreatic serotoninoma" or "serotonin-producing tumor of the pancreas" have been suggested as possible alternatives. Its growth characteristics may be related more to its cell of origin than to its extent of hormone secretion. Not all of the tumors result in recognizable hyperserotoninemia.

Adult↗
PubMed1997

Chylous ascites. A late complication of massive peripancreatic necrosis.

A 43-yr-old female underwent a normal endoscopic retrograde cholangiopancreatography (ERCP) because of ill-defined abdominal discomfort. A life-threatening pancreatitis with massive peripancreatic necrosis ensued, necessitating multiple necrosectomies. A colonic fistula required a temporary colostomy. Thirty-three months after onset of pancreatitis, although seemingly stable, she developed a massive chylous ascites, the fluid of which had a lipid content of approx 8000 mg%. Her serum cholesterol and triglyceride levels remained normal. During her third postpancreatitis year, while under observation and without operative intervention, the ascites began to clear slowly, almost completely clearing over the ensuing 16 mo. No comparable syndrome has been detected in a literature review, although eight patients with chylous ascites, possibly associated with pancreatitis, were identified. Since the senior author, in a career in pancreatic surgery, had not previously encountered the problem and since its natural history in this patient revealed spontaneous improvement, its description seems worthwhile.

Chylous Ascites↗
PubMed1997

Pancreatojejunostomy: leakage is a preventable complication of the Whipple resection.

BACKGROUND: Leakage of the pancreaticojejunal anastomosis has been a major complication after pancreaticoduodenectomy (Whipple operation), frequently reported in an incidence of 5 percent to 15 percent. The most widely used techniques of anastomosis have been variations of end-to-end pancreaticojejunostomy. Complicating 152 end-to-end anastomoses, done by me (including 98 for carcinoma of the pancreas or ampulla), were 5 pancreatic anastomotic leaks; the fifth patient died of this complication. STUDY DESIGN: The death resulting from a pancreatic anastomotic fistula led me to change my technique to an end of the pancreas to side of the jejunum, mucosa-to-mucosa, pancreaticojejunostomy (intubated), a modification of the technique described by Cattell and used since 1985 by me in 56 consecutive patients. Patients were monitored for clinical evidence of a pancreatic fistula, including evaluation of amylase content in serum and, in most, in peritoneal drainage. Pancreatography through the exteriorized pancreatic catheter was possible if deemed advisable. RESULTS: No pancreatic duct was too small or pancreas too soft to permit effective anastomosis. No clinical evidence developed of a pancreatic fistula, "sentinel bleed," or acute pancreatitis, and no patient was recognized to have a high amylase content in the peripancreatic peritoneal drainage. Results of the pancreatogram were negative in three patients with peripancreatic infections and in one with severe cholestasis. CONCLUSIONS: Although consensus among surgeons does not exist as to technique of pancreatic anastomosis, the end-to-side, mucosa-to-mucosa pancreaticojejunostomy, intubated, has proved safer in my experience than end-to-end pancreaticojejunostomy. The experience has led me to believe that the technique may reduce the incidence of this fistula and contribute to making pancreaticojejunal leakage a preventable complication.

Anastomosis, Surgical↗