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Biomedical subjects

A B Thomson

Publications and source records attributed to A B Thomson.

At least 19 recordsLinked to original sources
PubMed2003

Is inhibin B a potential marker of gonadotoxicity in prepubertal children treated for cancer?

BACKGROUND AND OBJECTIVE: Chemotherapy treatment of childhood cancer may impair gonadal function, which may be manifested only in adulthood as permanent sterility. Detection of gonadal dysfunction in prepubertal children has been hampered by the absence of a sensitive marker. Inhibin B is secreted by small antral follicles and Sertoli cells in females and males, respectively, and may be a marker of gonadal function in prepubertal children. The aim of this pilot study was to evaluate inhibin B in relation to sensitive measurements of gonadotrophins as markers of the early gonadotoxic effects of chemotherapy in prepubertal children treated for cancer. STUDY DESIGN AND SUBJECTS: Twenty-five prepubertal children (9 females), median age 4.5 years (range 1.2-12.8 years) with cancer (16 solid tumours, nine acute lymphoblastic leukaemia, ALL) were studied longitudinally. Blood samples were collected before and during chemotherapy (solid tumours) or immediately following induction and first intensification (ALL). Post-treatment (1-6 months) samples were collected in 12 of the patients (5 females). MEASUREMENTS: Dimeric inhibin B was measured by double antibody enzyme-linked immunosorbent assay (ELISA). FSH and LH were measured by sensitive time-resolved immunofluorescence. RESULTS: Girls: Pretreatment inhibin B was slightly high in one girl but normal for age and sex in all others: median 16.1 (range 9.4-186.2) ng/l, median SD score +0.2 (-1.3 to +2.6). Inhibin B decreased to undetectable levels (< 8 ng/l) in 8/9 girls during treatment (P = 0.03), with no accompanying rise in FSH or LH. Post-treatment recovery of inhibin B was variable: median 16.1 (range < 8.0-44.2) ng/l, median SD score +0.1 (range < -2.4 to +1.8). Sustained undetectable inhibin B levels were observed in 2/5 girls with correspondingly elevated FSH concentrations (11.8 and 10.9 U/l). Boys: Inhibin B was normal for age and sex in all boys before treatment with no significant change during or after treatment (medians 93 ng/l, 85 ng/l and 94 ng/l, SD scores -0.3, -0.6 and -0.2, respectively). Inhibin B decreased to undetectable levels in one boy post-treatment with no accompanying increase in FSH or LH. CONCLUSIONS: In prepubertal girls with cancer, chemotherapy is associated with suppression of inhibin B, usually transient, which may indicate arrest of follicle development. Sustained suppression of inhibin B following treatment may be indicative of permanent ovarian damage. In prepubertal boys, chemotherapy had little immediate effect on Sertoli cell production of inhibin B, although one boy showed a delayed effect. Inhibin B, together with sensitive measurements of FSH, may be a potential marker of the gonadotoxic effects of chemotherapy in prepubertal children with cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

The radiosensitivity of the human oocyte.

BACKGROUND: We determined the best model available for natural follicle decline in healthy women and used this to calculate the radiosensitivity of the human oocyte. METHODS: Ovarian failure was diagnosed in six patients with a median age of 13.2 years (range 12.5-16.0) who were treated with total body irradiation (14.4 Gy) at 11.5 years of age (4.9-15.1). We previously estimated the dose of radiation required to destroy 50% of the oocytes (LD(50)) to be <4 Gy. This estimate is an oversimplification, because decay represents an instantaneous rate of temporal change based upon the remaining population pool, expressed as a differential equation: dy/dx = -y[0.0595 + 3716/(11780 + y)], with initial value y(0) = 701 200. RESULTS: Solving the differential equation, we have estimated the number of follicles left after irradiation given as sol(51 - s + r), where r equals age at treatment, s equals age at diagnosis of ovarian failure, and 51 years is the average age of menopause. The surviving fraction of oocytes as a percentage is 100 times this value divided by sol(r). The mean surviving fraction for the six cases is 0.66%. We obtain a function, g(z), which decreases in value from 100% at zero dosage to mean value at dosage z = 14.4 Gy. We have g(z) = 10(mx+c), where c = log(10)100 = 2, and m = [log(10)(0.66) - c]/14.4. Solving g(z) = 50 gives an LD(50) of 1.99. CONCLUSIONS: Based on new data and a revised mathematical model of natural oocyte decline, we have determined the surviving fraction of oocytes following irradiation and estimate the LD(50) of the human oocyte to be <2 Gy.

Adolescent↗
PubMed2003

Preservation of fertility in children treated for cancer.

As treatment for childhood cancer has become increasingly successful, adverse effects on reproductive function are assuming greater importance. Preservation of fertility before treatment must be considered in all young patients at high risk of infertility, and provision of such services requires collaboration between oncology centres and assisted conception units. The UK Children's Cancer Study Group is planning to audit current management of preservation of reproductive function in young patients with cancer, and the British Fertility Society is preparing a voluntary code of best practice to guide and inform clinicians and scientists. Limitation of radiation exposure by shielding of the testes and ovaries should be practiced where possible and sperm banking should be offered to all sexually mature boys at risk of infertility. The rapidly advancing experimental techniques for harvesting of gonadal tissue must be considered and embarked on without unrealistic expectations, although future utilisation of the tissue is unlikely to be realised until the next decade.

Antineoplastic Agents↗
PubMed2002

Treatment of paediatric Hodgkin's disease. a balance of risks.

Hodgkin's disease is one of the commoner malignancies presenting in adolescence and young adulthood and is curable in the majority of cases. A number of therapeutic regimens have been used successfully, often at the expense of the development of side-effects in later life, including second malignancies, infertility and cardiac disease. We discuss the challenge faced by paediatric oncologists today in finding the balance between maximising cure and minimising the late effects.

Adolescent↗
PubMed2002

Investigation of suppression of the hypothalamic-pituitary-gonadal axis to restore spermatogenesis in azoospermic men treated for childhood cancer.

BACKGROUND: Does suppression of the hypothalamic-pituitary-gonadal (HPG) axis restore spermatogenesis in men rendered azoospermic following treatment of childhood cancer? METHODS: Seven men with azoospermia secondary to treatment for childhood cancer, median age (range), 22.2 (18-25.3) years, aged 10.4 (4.4-13.3) years at original diagnosis, participated. Each subject underwent semen analysis and testicular biopsy, followed by treatment with medroxyprogesterone acetate (MPA), 300 mg i.m. repeated after 12 weeks, with 800 mg testosterone pellets s.c. on day 1 to suppress the HPG axis. Hormone and semen analysis was performed every 6 weeks for 48 weeks. A second testicular biopsy was performed at week 48. RESULTS: Before HPG axis suppression, mean +/- SEM plasma LH was 9.0 +/- 1.8 U/l, testosterone 17.9 +/- 1.5 nmol/l and FSH 22.4 +/- 4.4 U/l. Median (range) venous plasma and seminal plasma inhibin B levels were 10.0 (7.8-35) and 11.2 (7.8-770) ng/l respectively. During HPG suppression, FSH and LH levels were undetectable for > or =12 weeks followed by a gradual return to pretreatment concentrations by 48 weeks. All men remained azoospermic at study completion and complete absence of germ cells on biopsies was demonstrated by immunocytochemistry for all specimens pre- and post-HPG axis suppression. CONCLUSIONS: HPG axis suppression with MPA-testosterone for > or =12 weeks did not restore spermatogenesis in azoospermic men treated with gonadotoxic radiotherapy and chemotherapy for childhood cancer.

Adolescent↗
PubMed2001

Small bowel review: normal physiology part 2.

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) numerous peptides are being identified which stimulate the proliferation and functional response of the small intestine to disease or resection, and may in time find a clinical use; (2) under usual in vivo conditions, absorption of nutrients has little effect on the paracellular movement of water; (3) the permeability of the intestine is modified by the function of the tight junctions, and measuring intestinal permeability may be useful to reflect the presence of disease; (4) the release of serotonin is influenced by cholinergic, adrenergic, and nonadrenergic, noncholinergic mechanisms, and serotonin agonists and antagonists may play an important future role in the treatment of motility disorders; (5) the use of endothelin receptor antagonists may be useful for the treatment of intestinal anaphylaxis; (6) the alterations in intestinal pH and motility in patients with Crohn's disease may influence the action of pH- or time-dependent release medications; and (7) patients with irritable bowel syndrome may also have abnormalities in gastric and small intestinal motility.

Adaptation, Physiological↗
PubMed2001

Small bowel review: diseases of the small intestine.

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practicing gastroenterologist. Selected important clinical learning points include the following: (1) glutamine may restore the AIDs-associated increased intestinal permeability to normal; (2) substance P is a major mediator of diarrhea caused by Costridium difficile toxin A, acting by binding to a G-protein-coupled receptor, and represents a possible 2therapeutic target; (3) the serological diagnosis of celiac disease has been greatly enhanced with the use of anti-endomysial antibody testing, and the recent antitransglutaminase; (4) a quarter of patients with celiac disease may have secondary pancreatic insufficiency and require enzyme replacement therapy; (5) in the patient with unexplained elevation in the serum transaminase concentration, consider celiac disease as an obscure possibility; (6) bosentan and endothelin receptor agonist may prove to be useful in reducing gut ischemia in patients with septic shock; and (7) the administration of recombinant human fibroblast growth factor-2 may prove to be useful to prevent radiation damage to the gastrointestinal tract.

Aging↗
PubMed2001

Small bowel review: normal physiology part 1.

In the past year there have been many advances in the area of small bowel physiology and pathology and therapy. In preparation for this review, over 1500 papers were assessed. The focus is on presenting clinically useful information for the practising gastroenterologist. Selected important clinical learning points include the following: (1) glucose absorption mediated by SGLT1 is controlled by mRNA abundance, as well as by posttranscriptional processes including protein trafficking; (2) inducers of cytochrome P-450 decrease glucose and fructose absorption and increase glucose consumption in the intestine; (3) the regulated release of nutrients from the stomach into the upper intestine ensures that the modest intestinal transport reserve capacity is not exceeded; (4) hepatocyte growth factor and short-chain fatty acids may enhance intestinal adaptation and prevent the atrophy seen when total parenteral nutrition is infused; (5) inhibitors of pancreatic lipase and phospholipase H2 may be useful clinically to reduce absorption as part of a treatment program for obesity and hyperlipidemia; (6) several membrane-bound and cytosolic proteins have been identified in the enterocyte as well as in the hepatocyte and may be the target for the future therapeutic manipulation of bile acid metabolism and control of hyperlipidemia; (7) suspect bile acid malabsorption in the patient with otherwise unexplained chronic diarrhea; (8) a proportion of lipid absorption is protein-mediated, and this opens the way to targeting these proteins and thereby therapeutically modifying lipid absorption; (9) a high protein diet may be useful to increase the intestinal absorption of drugs transported by the H+/dipeptide cotransporter; (10) a metal transporter DCT1 has been identified, and this may open the way to a better understanding of disorders of, for example, iron and zinc metabolism; (11) the nutrient transporters such as SGLT1 are responsible for a portion of the intestinal absorption of water; (12) the influence of nitric oxide on intestinal water absorption and secretion depends on its concentration; (13) a trial of bile acid-sequestering agent may prove useful in the treatment of the patient who experiences diarrhea while taking an enteral diet; (14) a proteolytic extract from pineapple stems may prove to be useful to treat diarrhea, although the mechanism of this effect remains to be established; and (15) the antisecretory effect of the new peptide, sorbin, needs to be tested in a clinical situation on patients with diarrhea. Other new and promising antidiarrheal agents include bromelain, an extract from pineapple stems, and igmesine, a final sigma ligand.

Acute-Phase Proteins↗
PubMed2001

The role of apolipoprotein A-IV in the regulation of food intake.

Apolipoprotein A-IV (apo A-IV) is a glycoprotein synthesized by the human intestine. In rodents, both the small intestine and liver secrete apo A-IV, but the small intestine is the major organ responsible for the circulating apo A-IV. Intestinal apo A-IV synthesis is markedly stimulated by fat absorption and appears not to be mediated by the uptake or reesterification of fatty acids to form triglycerides. Rather, the formation of chylomicrons acts as a signal for the induction of intestinal apo A-IV synthesis. Intestinal apo A-IV synthesis is also enhanced by a factor from the ileum, probably peptide tyrosine-tyrosine. The inhibition of food intake by apo A-IV is mediated centrally. The stimulation of intestinal synthesis and the secretion of apo A-IV by lipid absorption are rapid; thus, apo A-IV likely plays a role in the short-term regulation of food intake. Other evidence suggests that apo A-IV may also be involved in the long-term regulation of food intake and body weight. Chronic ingestion of a high-fat diet blunts the intestinal apo A-IV response to lipid feeding and may explain why the chronic ingestion of a high-fat diet predisposes both animals and humans to obesity.

Animals↗
PubMed2001

The dyspepsia alphabet: DU, GU, GERD, NERD, NUD/FD and UD.

The care of patients with dyspepsia may be almost as confusing as the many terms that are used to describe this very common symptom. A symptom-based approach may prove to be ideal for the patient with undiagnosed dyspepsia. This brief overview describes some of the many terms used to describe dyspepsia. Clearly, new treatment algorithms are needed for the care of patients with undiagnosed dyspepsia seen in a primary care setting.

Dyspepsia↗
PubMed2001

Ranitidine bismuth citrate.

Recognition of the relationship between Helicobacter pylori infection and the development of gastroduodenal disease has increased greatly in recent years. To avoid complications of H pylori infection, such as the development of recurrent duodenal and gastric ulcers, effective therapies are required for eradication of the infection. This article reviews ranitidine bismuth citrate (RBC), a novel complex of ranitidine, bismuth and citrate, which was developed specifically for the purpose of eradicating H pylori. Dual therapy with RBC in combination with clarithromycin for 14 days yields eradication rates of 76%. Triple therapy bid for one week with a proton pump inhibitor, clarithromycin and either amoxicillin or a nitroimidazole (tinidazole or metronidazole) is advocated as the treatment of choice for H pylori eradication. Analogous regimens with RBC in place of proton pump inhibitors show effective eradication rates in comparative studies and with pooled data. RBC, used alone or in combination with other antibiotics, appears to be a safe and effective drug for the treatment of H pylori infection. Bismuth levels do not appear to rise to toxic levels.

Amoxicillin↗
PubMed2001

Small bowel review: Part II.

In the past year, there have been many advances in the area of small bowel physiology and pathology. In preparation for this review, over 1500 papers were assessed. Some have been selected and reviewed, with a particular focus on presenting clinically useful information for the practising gastroenterologist. Relevant review articles have been highlighted, and important clinical learning points have been stressed. The topics are varied in scope and wherever possible show a logical progression from basic physiology to pathophysiology to clinical disorders and management.

Adaptation, Physiological↗
PubMed2001

Gastro-Oesophageal reflux in the elderly: role of drug therapy in management.

Gastro-oesophageal reflux disease (GORD) is common in the elderly. The presenting symptoms of heartburn and regurgitation, so common in the young, are less frequent in the elderly. Common symptoms of GORD in the elderly are dysphagia, vomiting and respiratory problems. Because of the higher risk of associated pathological oesophageal lesions in the older person presenting with symptoms suggestive of GORD, oesophagogastroduodenoscopy must be performed earlier in their clinical course. There is only a poor correlation between the severity of the symptoms and the severity of the associated oesophagitis. Whereas lifestyle modifications are important in individuals with GORD, the use of proton pump inhibitors is recommended to heal the underlying pathology, to resolve the patient's symptoms, to prevent complications, and to improve the quality of life.

Age Factors↗
PubMed2000

Variability of the intestinal uptake of lipids is genetically determined in mice.

The response of the plasma cholesterol concentration to changes in dietary lipids varies widely in humans and animals. There are variations in the in vivo absorption of cholesterol between different strains of mice. This study was undertaken in three strains of inbred mice to test the hypotheses that: (i) there are strain differences in the in vitro uptake of fatty acids and cholesterol and (ii) the adaptability of the intestine to respond to variations in dietary lipids is genetically determined. An in vitro intestinal ring technique was used to assess the uptake of medium- and long-chain fatty acids and cholesterol into jejunum and ileum of adult DBA/2, C57BL6, and C57L/J mice. The jejunal uptake of cholesterol was similar in C57L/J, DBA/2, or C57BL6 fed ad libitum a low-fat (5.7% fat, no cholesterol) chow diet. This is in contrast to a previous demonstration that in vivo cholesterol absorption was lower in C57L/J than in the other murine strains. The jejunal uptake of several long-chain fatty acids was greater in DBA/2 fed for 4 wk the high-fat (15.8% fat and 1.25% cholesterol) as compared with the low-fat diet. Furthermore, on the high-fat diet, the uptake of many long-chain fatty acids was higher in DBA/2 than in C57BL6 or C57L/J. The differences in cholesterol and fatty acid uptake were not explained by variations in food uptake, body weight gain, or the weight of the intestine. In summary: (i) there are strain differences in the in vitro intestinal uptake of fatty acids but not of cholesterol; (ii) a high-fat diet enhances the uptake of long-chain fatty acids in only one of the three strains examined in this study; and (iii) the pattern of strain- and diet-associated alterations in the in vivo absorption of cholesterol differs from the pattern of changes observed in vitro. We speculate that genetic differences in cholesterol and fatty acid uptake are explained by variations in the expression of protein-mediated components of lipid uptake.

Animals↗
PubMed2000

Are the orally administered proton pump inhibitors equivalent? A comparison of lansoprazole, omeprazole, pantoprazole, and rabeprazole.

Four proton pump inhibitors (PPIs) are currently marketed in various parts of the world, and all of these (lansoprazole, omeprazole, pantoprazole, and rabeprazole) are available for prescription use in the United States. As a therapeutic group, the PPIs are highly useful for the relief of symptoms and healing of gastroesophageal reflux disease, gastric and duodenal ulcer disease, eradication of Helicobacter pylori infection, prevention and treatment of nonsteroidal anti-inflammatory drug (NSAID)-associated damage, management of hypersecretory states such as Zollinger-Ellison syndrome, and care of patients with non-variceal upper gastrointestinal bleeding, or non-ulcer dyspepsia. The pathophysiologic basis of these management benefits lies in the potent gastric acid inhibitory effects of the PPIs. There are differences between the PPIs in their pharmacokinetics, pharmacodynamics, influence by food and antacids, clinical efficacy, and potential for drug interactions. It is not always clear whether these often subtle variations are necessarily of clinical importance. The physician's choice of one PPI over another must rest with her/his interpretation of the clinical importance of the generally small differences between PPIs, their approval for treatment of specific clinical indications within the physician's practice jurisdiction, and the strength of the evidence based on the quantity and quality of the supporting clinical trials.

2-Pyridinylmethylsulfinylbenzimidazoles↗