Search PubMed⌕ Search

Biomedical subjects

N Hudson

Publications and source records attributed to N Hudson.

At least 37 records · Page 2Linked to original sources
PubMed1998

Steroid contents of and steroidogenesis in vitro by the developing gonad and mesonephros around sexual differentiation in fetal sheep.

The aim of the present study was to establish whether the steroids, progesterone, androstenedione, testosterone and oestradiol, were present in the mesonephric-gonadal complex of female and male sheep fetuses around sexual differentiation (that is, from day 28 to day 45 of gestation, with sexual differentiation occurring at approximately day 32). A second aim was to test whether the mesonephric-gonadal complex, mesonephros (days 35-45 only) and gonad (days 35-45 only) were capable of steroid synthesis in vitro. The steroid contents in the mesonephric-gonadal complex were not detectable before sexual differentiation. However, from day 35 of gestation onwards, the mesonephric-ovarian complex contained mainly oestradiol and the mesonephric-testicular complex contained mainly testosterone: from day 35 until day 45 the increase in content of these two steroids exceeded the increase in the mass of tissue by more than fivefold. From day 40 to day 45 of gestation, the contents of the other steroids in the pathways to oestradiol increased progressively in both sexes but more in parallel with the increase in tissue mass. In contrast to the steroid contents in the tissue at recovery, the mesonephric-gonadal tissue from both sexes in tissue culture was able to synthesize most steroids before and after sexual differentiation and also to metabolise supplementary androstenedione to oestradiol. These findings suggest that many, if not all, of the steroidogenic enzymes in the pathway from cholesterol to oestradiol are present before sexual differentiation. Most of the aforementioned steroids were present in detectable amounts in isolated mesonephros and gonad of both sexes after sexual differentiation. Moreover, for both the isolated mesonephros and gonad, there were increases in the mean contents of most steroids after culture relative to the contents in the tissues at recovery. These data suggest that the mesonephros, as well as the gonad, in both sexes is capable of synthesizing steroid. It is concluded that, in the sheep fetus, the female and male gonads are steroidogenically active after sexual differentiation, that the steroidogenic enzymes develop before sexual differentiation, and that the mesonephros is a site of steroid synthesis.

Androstenedione↗
PubMed1997

Famotidine for healing and maintenance in nonsteroidal anti-inflammatory drug-associated gastroduodenal ulceration.

BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are strongly associated with gastroduodenal ulceration. How to manage patients with NSAID-associated ulcers is a common clinical dilemma. High-dose famotidine in the healing and maintenance of NSAID-associated gastroduodenal ulceration was therefore evaluated. METHODS: One hundred four patients with rheumatoid or osteoarthritis who had gastroduodenal ulceration received famotidine, 40 mg twice daily. Sixteen patients stopped and 88 continued their NSAID treatment. Ulcer healing was assessed endoscopically at 4 and 12 weeks. Seventy-eight NSAID users with healed ulcers were then randomized to receive 40 mg twice daily famotidine or placebo and underwent endoscopy at 4, 12, and 24 weeks. RESULTS: Cumulative ulcer healing rates at 12 weeks were 89.0% (95% confidence interval [CI], 82.3%-95.7%) for patients who continued NSAID treatment and 100% (95% CI, 82.9%-100.0%) for those who stopped. The subsequent estimated cumulative gastroduodenal ulcer relapse over 6 months for NSAID users who took placebo was 53.5% (95% CI, 36.6%-70.3%). This was reduced to 26.0% (12.1%-39.9%) in patients taking famotidine (P = 0.011). CONCLUSIONS: High-dose famotidine is effective ulcer healing therapy in patients who stop or continue NSAID treatment and significantly reduced the cumulative incidence of gastroduodenal ulcer recurrence compared with placebo when given as maintenance therapy.

Adult↗
PubMed1997

Effect of sucralfate on aspirin induced mucosal injury and impaired haemostasis in humans.

BACKGROUND: Sucralfate does not have potent anti-ulcerogenic actions in users of non-steroidal anti-inflammatory drugs (NSAIDs). However, sucralfate may influence intragastric haemostasis favourably. AIM: To investigate separately the effects of sucralfate on acute gastric and duodenal injury and on changes in intragastric bleeding induced by aspirin. METHOD: On three occasions, 24 healthy volunteers received three days' treatment with aspirin 900 mg twice daily together with placebo, sucralfate 2 g twice daily or sucralfate 1 g four times daily. Injury was assessed endoscopically and bleeding by spontaneous and biopsy induced bleeding intragastric washings. Ex vivo prostaglandin E2 (PGE2) synthesis and serum thromboxane were measured by using radioimmunoassay. RESULTS: Aspirin significantly inhibited ex vivo gastric mucosal PGE2 synthesis, reduced serum thromboxane, caused gastric erosions, and increased spontaneous and biopsy induced bleeding. Sucralfate had no significant effects on endoscopic injury but sucralfate 1 g four times daily significantly reduced spontaneous and biopsy induced bleeding. Similar trends were seen with sucralfate 2 g twice daily but the results were less consistent. CONCLUSION: Sucralfate does not affect aspirin induced acute gastric mucosal injury but reduces aspirin associated intragastric bleeding.

Acute Disease↗
PubMed1997

Catastrophic haemorrhage in a case of paediatric primary antiphospholipid syndrome and factor II deficiency.

The first case of primary antiphospholipid syndrome associated with recurrent life-threatening haemorrhages, due to the coexistence of acquired prothrombin deficiency, is described. Attention is drawn to the difficulty in diagnosing this situation, and therapeutic options are reviewed. Evidence is presented that implicates prothrombin as the protein cofactor for this lupus anticoagulant.

Adolescent↗
PubMed1996

Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.

BACKGROUND: Acid suppression with famotidine, a histamine H2-receptor antagonist, provides protection against gastric injury in normal subjects receiving short courses of aspirin or naproxen. The efficacy of famotidine in preventing peptic ulcers in patients receiving long-term therapy with nonsteroidal antiinflammatory drugs (NSAIDs) is not known. METHODS: We studied the efficacy of two doses of famotidine (20 mg and 40 mg, each given orally twice daily), as compared with placebo, in preventing peptic ulcers in 285 patients without peptic ulcers who were receiving long-term NSAID therapy for rheumatoid arthritis (82 percent) or osteoarthritis (18 percent). The patients were evaluated clinically and by endoscopy at base line and after 4, 12, and 24 weeks of treatment. The evaluators were unaware of the treatment assignment. The primary end point was the cumulative incidence of gastric or duodenal ulceration at 24 weeks. RESULTS: The cumulative incidence of gastric ulcers was 20 percent in the placebo group, 13 percent in the group of patients receiving 20 mg of famotidine twice daily (P = 0.24 for the comparison with placebo), and 8 percent in the group receiving 40 mg of famotidine twice daily (P = 0.03 for the comparison with placebo). The proportion of patients in whom duodenal ulcers developed was significantly lower with both doses of famotidine than with placebo (13 percent in the placebo group, 4 percent in the low-dose famotidine group [P = 0.04], and 2 percent in the high-dose famotidine group [P = 0.01]). Both doses of famotidine were well tolerated. CONCLUSIONS: Treatment with high-dose famotidine significantly reduces the cumulative incidence of both gastric and duodenal ulcers in patients with arthritis receiving long-term NSAID therapy.

Adult↗
PubMed1996

Comparison of effects of calcium carbasalate and aspirin on gastroduodenal mucosal damage in human volunteers.

Calcium carbasalate is a therapeutically active salicylate which seems to cause less gastroduodenal mucosal damage than aspirin in laboratory animals. This endoscopist-blinded, randomised, cross over trial aimed to compare acute gastric mucosal damage in 20 healthy volunteers treated with acetyl salicylic acid (ASA) (650 mg three times daily) and effervescent calcium carbasalate (ECC) (826.8 mg three times daily) bioequivalent to 650 mg ASA over a five day period. Endoscopy was performed immediately before treatment and on day 5 of each treatment. Serum salicylate, thromboxane B2, and gastric mucosal prostaglandin E2 (PGE2) concentrations were measured after endoscopy. ECC caused fewer gastric mucosal erosions than ASA. The total number of gastric erosions was 23.8 (16.1) in the ASA treated subjects compared with 9.1 (8.7) in ECC treated subjects (p = 0.004). Differences between ASA and ECC were significant for both the gastric antrum and body, and for both haemorrhagic and non-haemorrhagic erosions. The mean gastric body Lanza score for mucosal damage was lower after ECC than ASA (p = 0.003). The visual analogue score for gastric body damage was lower for ECC (16.9 mm (15.9)) than for ASA (32.7 mm (20.8)), p = 0.008. Serum salicylate concentrations were similar after both preparations (ASA: 66 (23) mg/l, versus ECC: 58 (17) mg/l, NS). Serum thromboxane B2 was similarly reduced using both preparations-97.2 (3.5)% inhibition with ASA, 95.2 (5.5)% inhibition with calcium carbasalate (NS). Suppression of gastric mucosal PGE2 synthesis was similar with both preparations (ASA: 83.4 (17.1)%; ECC 84.3 (12.9)%; NS). It is concluded that ECC causes significantly less gastroduodenal mucosal damage than ASA administered at bioequivalent doses as judged by serum salicylate, serum thromboxane, and mucosal PGE2 values. ECC may therefore be a less harmful alternative treatment to plain ASA.

Adolescent↗
PubMed1996

The management of variceal bleeding.

Fastidious resuscitation is essential in the initial management of acute variceal bleeding and requires adequate monitoring. Where endoscopic services are available diagnostic endoscopy should be performed ideally within 4-6 hours of admission and endoscopic therapy with injection sclerotherapy or binding ligation performed. Treatment to prevent early rebleeding will require further endoscopic treatment and possibly adjuvant vasoconstrictor therapy (somatostatin/octreotide or glypressin). Where endoscopy is unavailable vasoconstrictor therapy and/or balloon tamponade should be started prior to transfer to a centre with endoscopic facilities. Treatment failures should be considered for TIPSS or surgery. Gastric varices are better treated endoscopically with bovine or human thrombin than sclerotherapy. For prevention of rebleeding, variceal obliteration with endoscopic band ligation or prophylactic beta blockade are the two optimal treatments, although candidates may be identified for TIPPS if rebleeding recurs. Only beta blockers have so far been shown to be of value as primary prophylaxis.

Acute Disease↗
PubMed1995

A novel ultrasonic aerosol generator.

An ultrasonic aerosol generator constructed from a domestic humidifier is described which has been used to produce liquid aerosols for physiological investigations. The instrument was constructed from a Pifco domestic humidifier modified to include an energy guide to direct the oscillations of the transducer through the coupling water, which would normally be aerosolized, onto a small membrane based sample chamber containing the liquid to be aerosolized. The size distribution of the aerosol produced was found to be between 2 and 6 mm, optimum for diffuse intrapulmonary deposition. Up to 4 ml/min of aqueous liquid was used; however the sample chamber could be made small enough to contain economic amounts of expensive material to administer by inhalation. The instrument has proved to be reliable over a period of three years.

Aerosols↗
PubMed1995

Diagnostic associations with hypermobility in rheumatology patients.

Although we have considerable knowledge of the demographic characteristics of hypermobile individuals in population studies, we have little understanding of the implications of hypermobility. In this rheumatology clinic-based study we assessed the prevalence, diagnostic associations and clinical features of hypermobility in consecutive newly referred patients. Hypermobility was identified in 50 of 378 patients (13.2%). The most common clinical diagnosis in the hypermobile patients, compared with controls (those without hypermobility), was soft tissue rheumatism observed in 67% vs 25% (P<0.001). Fibromyalgia syndrome was the common specific rheumatological diagnosis in 30% vs 8% (P<0.001) and inflammatory arthritis the least common diagnosis in 4% vs 32% (P<0.001) of hypermobile versus non-hypermobile patients, respectively. Hypermobile patients complained of previous pain, including widespread or multiple localized sites of pain and spinal pain. Although clinic-based studies may not accurately reflect disease patterns as seen in the population, these results suggest an association between hypermobility and soft tissue rheumatic complaints and should be useful to the clinical rheumatologist.

Adolescent↗
PubMed1995

Successful Helicobacter pylori eradication incorporating a one-week antibiotic regimen.

BACKGROUND: The optimum regimen for the eradication of Helicobacter pylori remains unclear. The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s. and metronidazole 400 mg t.d.s. given for the first 7 days, in the treatment of H. pylori associated peptic ulcer disease. RESULTS: One hundred and thirty-two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter-quartile range: 36-58 years). H. pylori was eradicated successfully in 109 of 130 patients (intention-to-treat: 83%; 95% confidence limits: 76-89%); per protocol: 85% (95% CI: 78-91%)). Ninety per cent of patients completed the full course of therapy. Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients. One patient developed pseudomembranous colitis requiring hospital admission. CONCLUSION: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen. Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.

Adult↗
PubMed1995

Late mortality in elderly patients surviving acute peptic ulcer bleeding.

Acute peptic ulcer bleeding is associated with a substantial short term mortality but it is generally assumed that in the modern era of effective medical treatment the longer term prognosis is good. This study evaluated 487 patients aged over 60 years who were discharged from Nottingham University and City Hospitals after admission for acute peptic ulcer bleeding during 1986-91 and 480 age and sex matched community controls. Follow up information was obtained from hospital and general practitioner records and from the National Health Service central register. Mortality was compared with control mortality and with rates expected for England and Wales. During a mean follow up of 34 months 142 (29%) of 487 patients died compared with 58 (12%) of 480 community controls and with 81.5 deaths expected (observed/expected (O/E) = 1.74, 95% confidence limits (CL) 1.5 to 2.1). Six years after admission the actuarial survival estimate was only 50% for ulcer patients compared with 76% for community controls and 69% expected. The increased mortality was similar in men and women and was greatest in the 60-74 year age group. Much of the excess mortality was accounted for by deaths from cancer (O/E 34/19.7 = 1.73; CL 1.2 to 2.4), from respiratory disease (O/E 28/10.9 = 2.57; CL 1.7 to 3.7), and in men from vascular disease (O/E 31/22.4 = 1.38; CL 0.9 to 2.0). Eight deaths resulted from recurrent ulcer complications and four deaths from gastric cancers undetected at the index admission. In conclusion, patients discharged after peptic ulcer bleeding had a substantially reduced life expectancy. The increased mortality was predominantly due to a variety of smoking related diseases rather than recurrent peptic ulcer complications. Deaths from recurrent peptic ulcer complications were infrequent and were less than reported in earlier years possibly reflecting prolonged and widespread used of H2 receptor antagonists.

Acute Disease↗
PubMed1995

Morbidity and treatment in elderly patients surviving hospital admission with bleeding peptic ulcer.

Bleeding peptic ulcer in the elderly is associated with use of non-steroidal, anti-inflammatory drugs (NSAIDs) and aspirin, presenting a therapeutic dilemma for the treatment of survivors. To determine the longterm morbidity of patients surviving bleeding peptic ulcer and their treatment, with particular reference to NSAID use, this study followed up 487 patients aged over 60 years, who survived an episode of bleeding peptic ulcer in Nottingham during 1986 to 1991. Information was gathered by evaluation of general practitioner and hospital records, scrutiny of death certificates, and postal questionnaire to surviving patients. Of 487 patients surviving a bleeding peptic ulcer, 345 were alive at the follow up, a mean 34.2 months after discharge. Of these 201 (58%) had taken NSAIDs before their ulcer bleed (104 non-aspirin NSAIDs, 77 aspirin, 20 both). Compared with non-users, the patients using NSAIDs at the time of presentation were significantly more likely subsequently to consult their general practitioner with locomotor symptoms (56% v 35%, p < 0.001) and receive further NSAIDs (34% v 13%, p < 0.001), but significantly less likely to consult their general practitioner for dyspepsia (31% v 54%, p < 0.001). Antiulcer drug use was widespread in both groups, with an overall point prevalence of 44%. Seventy five patients received NSAIDs during the follow up period (69% with coprescription of antiulcer drugs, usually H2 antagonists). Recurrent peptic ulcer, ulcer complications, and ulcer related deaths were uncommon. Antiulcer drug use was lower in those with ulcer recurrence compared with the point prevalence in those without (17% v 44%, p < 0.05). Patient questionnaire responses confirmed a high level of locomotor symptoms especially in patients previously admitted with NSAID associated ulcer bleeding. In conclusion, in patients surviving peptic ulcer bleeding, recurrent ulcer complications and death seem to be lower than reported by studies that preceded the advent of antiulcer drugs. It is suggested that this low incidence may be a consequence of their use. Granted the low level of recurrent ulceration and the high level of locomotor symptoms in patients studied, current treatment may unduly emphasise the importance of stopping NSAIDs in this group of patients.

Aged↗
PubMed1995

Angiogenesis in gastric ulcers: impaired in patients taking non-steroidal anti-inflammatory drugs.

Non-steroidal anti-inflammatory drug (NSAID) therapy is associated with delayed gastroduodenal ulcer healing. In rats the degree of angiogenesis (new vessel formation) within the ulcer bed correlates strongly with the extent and speed of ulcer healing and may be inhibited by NSAIDs. This study therefore assessed the vascularity of 38 antral gastric ulcers immunohistochemically, using CD31 a vascular endothelial cell marker, in 17 patients taking NSAIDs and 19 control patients. In the superficial granulation tissue NSAID therapy was associated with a significant reduction in the median number of capillaries (13.5 (IQR: 9.5-18) v 23.5 (14-31) (p < 0.005)), number of vessel buds (6 (4-12.5) v 17 (12-23) (p < 0.05)), and maximum vessel diameter (29 (20.75-30.75) v 33.75 (24-45) (p < 0.05)) when compared with controls. In deep granulation tissue NSAID therapy was similarly associated with a significant reduction in the number of capillaries (9 (6.5-12) v 14 (9-19.25) (p < 0.04)), number of vessel buds (5 (3.5-8.5) v 13 (7-16.5) (p < 0.01)), and maximum vessel diameter (23 (18-20.5) v 33 (21.5-45) (p < 0.02)). There were no differences in vascularity in the adjacent glandular mucosa. Impairment of angiogenesis may be an important mechanism of NSAID related delayed ulcer healing.

Aged↗
PubMed1995

Basic fibroblast growth factor treatment for non-steroidal anti-inflammatory drug associated gastric ulceration.

An open, pilot study tested the safety and efficacy of an acid stable form of the angiogenic protein basic fibroblast growth factor (bFGF) for healing of non-steroidal anti-inflammatory drug (NSAID) associated gastric ulcers in five patients with nine gastric ulcers that were resistant to conventional treatment (4) or had relapsed (5). Oral bFGF treatment for four weeks was safe and well tolerated. There was no evidence of systemic absorption. After four weeks, four ulcers had healed and there was a 89 (3)% mean (SEM) reduction in the area of the others. A controlled, comparative trial of this novel growth factor treatment is warranted.

Anti-Inflammatory Agents, Non-Steroidal↗