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Biomedical subjects

D Forman

Publications and source records attributed to D Forman.

At least 127 records · Page 7Linked to original sources
PubMed1995

Variability in serum pepsinogen levels in an asymptomatic population.

OBJECTIVE: To investigate the variability in serum pepsinogen levels in an asymptomatic population. DESIGN: Cross-sectional survey of 420 men aged 18-63 years, without symptoms or a history of gastric disease, recruited from four factories in Stoke-on-Trent. METHODS: During an interview, data on history of gastric health, 'lifestyle' and occupation were collected, blood samples were taken for measurement of serum pepsinogen and anti-Helicobacter pylori antibody levels and height and weight were measured. RESULTS: Extreme (low/high) levels of pepsinogens A and C, indicative of chronic gastritis, were found in 24 (5.7%) and 61 (14.5%) of the participants, respectively. Low A-C ratios, indicative of moderate or severe gastric atrophy, were found in 13 (3.1%) participants. Of the variables examined, Helicobacter pylori serology had the strongest influence on serum pepsinogen levels. Serum pepsinogen A and C levels were significantly higher in the 33.6% of participants who were seropositive. The effect was more marked for pepsinogen C; thus, A-C ratios were lower in seropositive individuals. In seronegative participants, both pepsinogen A and pepsinogen C levels increased with increasing age; pepsinogen A levels increased with increasing height and were higher in smokers, but decreased with increasing weight. The effect of smoking on pepsinogen A levels was also detectable in seropositive individuals, but was considerably less marked. Among seronegative participants, those employed on the 'shop-floor' in manual jobs had higher serum pepsinogen C levels and lower A-C ratios than office-based workers. CONCLUSION: H. pylori serology was a major source of variation in serum pepsinogen levels, but causes of gastritis other than H. pylori were indicated. Independent of these effects, serum pepsinogen levels may also vary with age, height and weight. Screening of serum pepsinogen levels in the general population may identify 5-15% who require further investigation. Other 'filters' may be required in conjunction with serum pepsinogen levels to identify those needing investigation for significant gastric pathology.

Adult↗
PubMed1994

Relation between infection with Helicobacter pylori and living conditions in childhood: evidence for person to person transmission in early life.

OBJECTIVES: To relate the prevalence of infection with Helicobacter pylori in adults to their living conditions in childhood to identify risk factors for infection. DESIGN: Prevalence study of IgG antibodies to H pylori (> 10 micrograms IgG/ml, determined by enzyme linked immunosorbent assay (ELISA)) and reported living conditions and other socioeconomic factors in childhood. SETTING: Three factories in Stoke on Trent. SUBJECTS: 471 male volunteers aged 18 to 65 years. MAIN OUTCOME MEASURES: Seroprevalence and variables in childhood. RESULTS: Seroprevalence of H pylori increased with age (22/74 (29.7%) at < 30 years v 29/46 (63%) at 55-65 years; P < 0.001 for trend) and was related to manual occupation (14/65 (21.5%) for non-manual v 162/406 (39.9%) for manual; P = 0.003). After data were adjusted for age and occupation subjects from large families, whose childhood homes were crowded or who regularly shared a bed in childhood, were significantly more likely to be seropositive (adjusted odds ratio (95% confidence interval) 2.15 (1.41 to 3.30) for crowding and 2.13 (1.38 to 3.30) for sharing a bed), but there was no relation with possession of a bathroom, inside toilet, refrigerator, or household pets in childhood. CONCLUSIONS: Close person to person contact in childhood is an important determinant of seroprevalence of H pylori in adulthood, suggesting that the infection is transmitted directly from one person to another and may be commonly acquired in early life.

Adolescent↗
PubMed1994

Cytokine intervention permits dose escalation of radioantibody. An analysis of myelostimulation by bolus versus continuous infusion of IL-1/GM-CSF.

BACKGROUND: The authors recently reported that a 12-day schedule (beginning 3 days before radioantibody treatment) of twice-daily dosing of rH-IL-1 (1 x 10(3) U/dose) and rM-GM-CSF (0.5 micrograms/dose) can reduce the magnitude and duration of radioantibody-induced myelosuppression, thereby permitting a 25-30% increase in the dose of radioantibody that can be administered without the dose proving lethal. In an effort to further reduce toxicity and escalate the tolerated dose, the authors altered the method of administration of cytokines from daily bolus dosing to continuous infusion by implantable osmotic pumps. METHODS: A control group of mice was compared to five groups of mice that either did or did not receive a 340 microCi dose of radioantibody, and received no cytokines, cytokines by bolus dosing, or cytokines by continuous infusion. For 4 weeks, peripheral white blood cell and thrombocyte counts and thymus and spleen weights were taken, marrow cell number was monitored, and marrow colony-forming unit activity was evaluated weekly in the untreated control mice and the treated mice. RESULTS: These studies demonstrated that after a dose of radioantibody, continuous dosing of cytokines resulted in higher white blood cell (WBC) and platelet values than if bolus delivery was used (day 7, WBC: 110% vs. 59%; day 14, WBC: 85% vs. 62%; day 21, WBC: 98% vs. 42%; day 7, platelets: 122% vs. 51%; day 14, platelets: 159% vs. 72%; day 21, platelets: 239% vs. 171%). A comparison of bolus versus continuous dosing in the absence of radioantibody indicated that spleen weight increased by 40-60% after continuous infusion of cytokines and by 20-25% after bolus dosing. The 20-30% decrease in thymus weight was similar with both dosing regimens. Colony-forming units (CFUs) in marrow increased from 30-35 in untreated mice to 50-55 in mice given cytokines by bolus injection, and to 150-180 in mice given continuous infusion of cytokines. Spleen CFUs exhibited an insignificant increase after bolus dosing of cytokines but increased almost fourfold after continuous dosing. Peak stimulation of marrow and spleen CFUs occurred 28 days after initiation of cytokine administration (2 weeks after cytokines administration was stopped). The probability of survival for 6 weeks after further dose escalation to 360 microCi I-131-MN-14 immunoglobulin G was 16.4% +/- 8.6% after bolus dosing and 58.1% +/- 11.3% after continuous infusion of cytokines. CONCLUSIONS: Although continuous infusion of cytokines proved to be a better method of reducing hematopoietic toxicity, further dose escalation of radioimmunotherapy using the "pump" method of cytokine delivery was not possible. Cytokine intervention by either mode of delivery permits a 25% dose intensification without the dose becoming lethal. Further escalation is not feasible, possibly because of other end organ toxicity.

Animals↗
PubMed1994

The epidemiology of low serum pepsinogen A levels and an international association with gastric cancer rates. EUROGAST Study Group.

BACKGROUND/AIMS: Low serum levels of pepsinogen A are indicative of chronic atrophy, a risk factor for gastric cancer. This study investigated the relationships between low pepsinogen A levels, Helicobacter pylori seropositivity, and gastric cancer rates in 17 populations worldwide. METHODS: In each center, about 200 randomly selected subjects (50 male and 50 female, aged 25-34 and 55-64 years) provided serum samples for pepsinogen analysis and H. pylori serology. RESULTS: Cumulative gastric cancer rates were associated with the prevalence of low pepsinogen A levels in men (coefficient, 0.15 [P = 0.06] for mortality; coefficient, 0.36 [P = 0.01] for incidence) but not women. The prevalence of low pepsinogen A levels was also correlated with H. pylori seropositivity in the older age group (r = 0.55; P = 0.02). Low pepsinogen A levels were significantly more common in the older group (7.5% vs. 2.1% in the younger group; P < 0.001), among women (5.5% vs. 4.1% in men; P = 0.04), and among nonsmokers (5.8% vs. 2.9% in current smokers; P = 0.001). CONCLUSIONS: Low pepsinogen A levels are more common in areas with a high seroprevalence of H. pylori and in men in areas with high rates of gastric cancer. The prevalence of low pepsinogen A levels increases with age, but the excess in women and nonsmokers could reflect factors other than gastric pathology.

Adult↗
PubMed1994

Metabolic polymorphisms in carcinogen metabolising enzymes and cancer susceptibility.

Molecular genetic analysis is providing us with enormous advances in understanding the pathogenesis of human diseases such as cancer. The study of familial disease and the subsequent mapping and identification of the mutations which contribute to disease susceptibility, is not only providing insights into the factors involved in the pathogenesis of the disease but also identifying new targets for therapy. It is now clear that human tumours result from a complex sequence of mutation events. Each individual step makes the mutated cell more independent of its normal growth regulatory processes, eventually resulting in the formation of a metastatic tumour. There are a multitude of biochemical changes that these mutations confer, which provide preneoplastic cells with a selection advantage. In addition to an increased rate of cell division, such changes may make the cells resistant to cytotoxic insult or to programmed cell death. They can also confer an increased ability to survive independent of a normal hormonal environment. It is now clear that all these types of change may contribute to tumour cell progression.

Cytochrome P-450 Enzyme System↗
PubMed1994

Testicular cancer.

Testicular cancer is a disease that predominantly affects young and middle aged men. Our data show that incidence rates have recently increased in men aged 15-54 years in all 13 populations examined, irrespective of whether the populations were at high, moderate or low underlying risk. The annual percentage increase in this age group between 1970 and 1985 varied from 1.9% in the West Midlands, UK, to 6.6% in Miyagi, Japan, with a median of 2.7%. Analysis of the data in two separate age bands, 15-34 and 35-54 years, shows that increases are occurring in both subgroups. This, together with analyses by histological category in Denmark and the West Midlands, UK, indicates that both teratomas and seminomas are increasing in incidence. In contrast to the pattern for incidence rates, testicular cancer mortality rates are now declining in all the nine national populations examined. The time from which mortality rates started to decline varies between populations, and in Poland, a reduction was not observed until the 1980-1985 period. This reflects delay in the uptake of effective chemotherapy for the treatment of teratomas. The decline in mortality, against a background of rapidly increasing incidence in most populations, emphasizes the appreciable improvements in prognosis associated with testicular cancer in recent decades. Although the epidemiology of testicular cancer strongly suggests the presence of environmental risk factors that may be controllable, our ignorance about the nature of these factors precludes any strategy of prevention. Early diagnosis and improved treatment will therefore remain a major focus for the control of this cancer. Our ability to treat testicular cancer is thus a major and necessary achievement given the increase in incidence.

Adolescent↗
PubMed1993

The cost of clinical placements.

Educational programmes for nurses and the allied professions have increasingly been located within the marketplace through the introduction of educational contracts. But the use of clinical placements and related costs are not addressed within such contractual arrangements. Dawn Forman and Jane Fox assess the advantages and disadvantages.

Allied Health Personnel↗
PubMed1992

Nitrate and N-nitrosoproline excretion in two Italian regions with contrasting rates of gastric cancer: the role of nitrate and other factors in endogenous nitrosation.

Exposure to nitrate and propensity for endogenous nitrosation were examined in 80 healthy males, aged 25-40 years, residing in areas of Italy with long-standing high (Florence) and low (Cagliari) rates of gastric cancer. Nitrate exposure was assessed by measurement of urinary nitrate excretion over 12 hr, and endogenous nitrosation was assessed using the N-nitrosoproline test (NPRO-test). Our hypothesis was whether the geographic variation in cancer rate correlated with nitrate exposure or nitrosating ability. Exposure to background sources of NPRO was significantly higher in the high-risk subjects (phi = 0.04) whereas no differences were found in exposure to nitrate or in urinary NPRO levels after L-proline loading (test NPRO levels). The regional difference in test NPRO was almost completely accounted for by background NPRO exposure. Examination of individual rather than grouped data revealed that exposure to nitrate was a major factor in NPRO formation. No other factors studied (age, dietary-questionnaire-assessed intake of anti-oxidant vitamins) had a significant effect. Geographical variation in gastric cancer risk did not, therefore, correlate with either nitrate exposure or propensity for endogenous nitrosation of L-proline.

Adult↗
PubMed1992

Familial testicular cancer: a report of the UK family register, estimation of risk and an HLA class 1 sib-pair analysis.

Forty-two families with two or more cases of testicular cancer have been reported to the UK Register for Familial Testicular Cancer, comprising two pairs of identical twins, 27 sets of other brothers (25 pairs, two triples), nine father-son pairs, two pairs of first cousins and two uncle-nephew pairs. In total 91 testicular tumours are described in 86 individuals (42 (46%) pure seminoma, 49 (54%) other germ cell tumours). The median age at diagnosis in these patients was significantly younger than that in a comparable series of non-familial patients (29 c.f. 32.5 years, P less than 0.01). In a case-control comparison of 794 testicular cancer patients, eight patients (1.0%) had a brother and four patients (0.5%) had a father with a previous diagnosis of testicular cancer at the time of their own diagnosis (and these families are all included in this report). Two out of 794 controls (0.3%) had a first degree relative with testicular cancer. The cumulative risk to a brother of a patient for developing testicular cancer by the age of 50 years was estimated to be 2.2% (95% C.I. 0.6-3.8%) which results in a relative risk of 9.8 (95% C.I. 2.8-16.7) in comparison with the general population. HLA Class I typing of 21 affected sib-pairs demonstrated four (19%) sharing two haplotypes, 13 pairs (62%) sharing one and four pairs (19%) sharing none. This did not differ significantly from the expected proportions of 25%/50%/25%. It is unlikely, therefore, that there is a major gene associated with testicular cancer predisposition within or closely linked to the major histocompatibility gene complex on chromosome 6.

Adolescent↗
PubMed1992

Locked patellar dislocation with vertical axis rotation. A case report.

Whereas traumatic lateral dislocation of the patella is a well-described clinical entity, other types of patellar dislocations, specifically those that involve patellar rotation, are unusual. These rare types also present a therapeutic problem in which reduction often requires a general anesthetic and, possibly, an open procedure. A 16-year-old boy sustained a laterally directed blow to his knee, resulting in dislocation of the patella. The patella had rotated 90 degrees in the vertical plane and became wedged against the lateral femoral condyle. Initial attempts at closed reduction in the emergency room and under general anesthesia in the operating room were unsuccessful, and the patient required open reduction. A similar type of dislocation has been described; however, the patella is usually intercondylar. The tear along the medial side was extensive enough to allow the patella to dislocate lateral to the lateral femoral condyle, making this a unique case. In these instances of rare patellar dislocation, the surgeon should be prepared to perform an open reduction, because attempts at closed reduction even with a general anesthetic may be unsuccessful.

Adolescent↗
PubMed1991

Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation.

OBJECTIVE: To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN: Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS: 29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS: 20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS: H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.

Adult↗
PubMed1991

N-nitrosoproline excretion in the presence and absence of gastric disease.

N-nitrosoproline (NPRO) excretion, an indicator of endogenous nitrosation, was measured in a group of hospital inpatients who were identified by endoscopy and gastric biopsy as either having gastric lesions or having healthy stomachs. NPRO was assayed in background 24-hour urine samples and samples collected after loading doses of nitrate and L-proline. The presence of gastric lesions was associated with altered gastric pH and concomitant changes in gastric juice nitrate and nitrite concentration. Gastric juice pH increased with increasing severity of gastric disease (P = 0.031) and patients with normal stomachs had a lower gastric pH than those with chronic atrophic gastritis (CAG) (3.0 vs. 6.5, P = 0.017). The changes in gastric juice nitrate concentration were in the reverse direction (P = 0.002 for trend) with normal patients having higher mean levels than CAG patients (12.7 vs. 5.5 micrograms/ml, P less than 0.0001). Nitrite concentration increased with severity of gastric disease but the results were not significant (normal, 82.9 vs. CAG, 223.4 ng/ml, P = 0.069). No association was found between the presence of gastric lesions and increased urinary NPRO excretion. Mutagenic activity was not detected in any of the gastric juice samples.

Adult↗