PubMed Health⌕ Search

Biomedical subjects

N Griffin

Publications and source records attributed to N Griffin.

At least 19 recordsLinked to original sources
PubMed2004

Quality of life in patients with chronic anal fissure.

OBJECTIVE: Little is known about the quality of life in patients with the distressing symptoms of chronic anal fissure. This was a prospective study assessing the physical and mental health of fissure patients before and after topical treatment. PATIENTS AND METHODS: New patients attending the fissure clinic were recruited prospectively into the study over a 2-month period. On first appointment, patients were given 2 questionnaires to complete: the Short-Form 36 Health Survey (SF-36) and a general questionnaire recording patients' demographic details, previous treatment, site and duration of fissure and symptoms on a visual analogue scale (VAS). Following an 8-week course of topical treatment, patients repeated the SF-36 and symptoms were again recorded on a VAS. Healing of fissure was noted. RESULTS: Fifty-four patients entered the study, of which 39 returned for follow-up; 16 male, 23 female; mean age 38.6 years (range 17-80 years). Median duration of fissure was 6 months (3 months - 10 years). Higher VAS ratings for fissure pain were associated with worse scores for all aspects of health-related quality of life, including mental health (P < 0.001), bodily pain (P < 0.001), vitality (P < 0.006) and social functioning (P < 0.001). Compared to age and gender matched norms for the SF-36, fissure patients had more bodily pain (P < 0.001, Wilcoxon) and poorer health perceptions (P < 0.02, Wilcoxon). Gender did not affect any of the SF-36 subscales. However, females did report significantly more bleeding (P = 0.05). On follow-up, healing was complete in 27 patients (69%). Symptoms of pain, bleeding and irritation were all significantly reduced in this group. Repeating the SF-36 showed an improvement in bodily pain, role-physical functioning and vitality (P < 0.05). CONCLUSION: Successful nonsurgical treatment of chronic anal fissure leads to symptomatic improvement and beneficially affects health-related quality of life.

Adolescent↗
PubMed2003

L-arginine-induced relaxation of the internal anal sphincter is not mediated by nitric oxide.

BACKGROUND: Topical application of L-arginine, the precursor of nitric oxide, reduces resting anal pressure without significant side-effects and may therefore be of benefit in the treatment of anal fissure. This in vitro study investigated the effect of L-arginine on sheep and human isolated internal anal sphincter (IAS) to ascertain the role played by nitric oxide and guanosine 3',5'-cyclic monophosphate. METHODS: Strips of sheep and human IAS were mounted in isolated organ baths. The effects on myogenic tone of increasing concentrations of L-arginine, D-arginine and other amino acids were evaluated. RESULTS: L-Arginine, D-arginine and other basic amino acids (L-lysine and L-ornithine) all caused a concentration-dependent reduction in myogenic tone. L-Arginine was the most effective and produced a mean(s.e.m.) maximal reduction in myogenic tone of 78.2(7.1) and 40.2(9.3) per cent in sheep and human tissue respectively. These responses were not affected by N(G)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, or 1H-[1,2,4]oxadiazolo[4,3-a]-quinoxalin-1-one, an inhibitor of soluble guanylyl cyclase. Changes in pH per se were unable to explain the relaxation fully, but an equiosmolar sodium chloride solution produced a concentration-response relationship similar to that of L-arginine. CONCLUSION: The ability of L-arginine to reduce myogenic tone is independent of nitric oxide. This effect may be partially pH dependent but the osmolality of the solution appears to be a major factor. Hyperosmolar solutions might be worthy of further investigation as agents that affect anal tone.

Anal Canal↗
PubMed2002

Topical L-arginine gel lowers resting anal pressure: possible treatment for anal fissure.

PURPOSE: Exogenous nitric oxide donors, such as glyceryl trinitrate, have been used as treatment for anal fissures; however, headaches develop in 60 percent of patients. Nitric oxide produced from the cellular metabolism of L-arginine mediates relaxation of the internal anal sphincter. This study investigated whether topical L-arginine gel reduces maximum anal resting pressure in volunteers. METHOD: In a two-center study, volunteers received a single topical dose of L-arginine or placebo (Aquagel ). Anal manometry was performed for two hours after application of 400 mg of L-arginine gel or placebo gel to the anal verge in 25 volunteers. Side effects were recorded after single application and also after repeated dosing for three days. RESULTS: L-Arginine reduced maximum anal resting pressure by 46 percent from a median of 65 cm of water to a minimal value of 35 cm of water ( P< 0.001, Wilcoxon's signed-rank test). The difference between L-arginine and placebo using repeated-measures testing was significant at P< 0.005. No side effects occurred with either gel; in particular, no episodes of headache were recorded. CONCLUSION: Topical L-arginine gel significantly lowers maximum anal resting pressure; its onset of action is rapid, and duration is at least two hours ( P< 0.01). L-arginine may have therapeutic potential, but further evaluation is needed before it can be used as a possible alternative treatment for chronic anal fissure.

Administration, Topical↗
PubMed2002

The role of topical diltiazem in the treatment of chronic anal fissures that have failed glyceryl trinitrate therapy.

OBJECTIVE: The treatment of anal fissures has evolved over the last 5 years with the development of topical treatments aimed at reducing sphincter hypertonia. This is thought to improve anal mucosal blood flow and promote healing of the fissure. This study reports the use of topical diltiazem in patients with chronic anal fissures that have failed previous treatment with topical 0.2% glyceryl trinitrate (GTN). PATIENTS AND METHODS: Forty-seven patients with chronic anal fissure who had previously failed at least one course of topical GTN were recruited prospectively from a single centre. Patients were instructed to apply 2 cm (approximately 0.7 g) of 2% diltiazem cream to the anal verge twice daily for eight weeks. Symptoms of pain, bleeding and itching were recorded on a linear analogue score prior to starting the cream and then repeated at 2 weekly intervals. Patients were asked to report side-effects throughout the study period. Healing of the fissure was assessed after 8 weeks of treatment. RESULTS: Forty-six patients completed treatment; of these, 22 had healed fissures (48%). Ten of the 24 patients with persistent fissures were symptomatically improved and wished no further treatment. Of the 14 patients who remained symptomatic, one was given a repeat course of 0.2% glyceryl trinitrate with subsequent healing of the fissure, 10 were recruited into an ongoing study involving injections of botulinum toxin into the internal anal sphincter and three were referred for surgery. CONCLUSION: This study shows that topical 2% diltiazem is an effective and safe treatment for chronic anal fissure in patients who have failed topical 0.2% GTN. The need for sphincterotomy can be avoided in up to 70% of cases.

Journal Article↗
PubMed1999

Requirement for B cell linker protein (BLNK) in B cell development.

Linker proteins function as molecular scaffolds to localize enzymes with substrates. In B cells, B cell linker protein (BLNK) links the B cell receptor (BCR)-activated Syk kinase to the phosphoinositide and mitogen-activated kinase pathways. To examine the in vivo role of BLNK, mice deficient in BLNK were generated. B cell development in BLNK-/- mice was blocked at the transition from B220+CD43+ progenitor B to B220+CD43- precursor B cells. Only a small percentage of immunoglobulin M++ (IgM++), but not mature IgMloIgDhi, B cells were detected in the periphery. Hence, BLNK is an essential component of BCR signaling pathways and is required to promote B cell development.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Antibodies raised by gastrimmune inhibit the spontaneous metastasis of a human colorectal tumour, AP5LV.

Both precursor forms of gastrin and mature amidated gastrin peptides can enhance proliferation of colorectal tumours and may regulate growth in an autocrine manner. The purpose of this study was to evaluate the effect of neutralization of precursor and amidated gastrin on primary and secondary in vivo growth of a human colorectal tumour. The human colorectal cell line, AP5LV, when injected into the muscle layer of the abdominal wall of severe combined immunodeficient (SCID) mice, grows as a well-vascularized primary tumour and metastasis to the lung. AP5LV expressed the precursor gastrin forms; progastrin and glycine-extended gastrin and gastrin/CCKB receptors, as assessed by immunocytochemistry. Gastrimmune is a gastrin immunogen in which the amino terminus of the gastrin-17 molecule is linked to diphtheria toxoid and induces antibodies which neutralise the amidated and glycine-extended forms of gastrin-17. Rabbit antiserum, raised against Gastrimmune, was administered intravenously into SCID mice bearing AP5LV tumours. Control animals were treated with antiserum raised against diphtheria toxoid only. Antibodies raised against Gastrimmune significantly limited the growth of primary AP5LV tumours, as assessed by median cross-sectional area (controls = 244 mm2; antibody-treated = 179 mm2; P = 0.033). In addition Gastrimmune-induced antiserum limited the growth of lung metastasis as assessed by nodule number (controls = 3.5; antibody-treated = 1.0; P = 0.0001) and nodule cross-sectional as assessed by image analysis (controls = 11.9 mm2; antibody-treated = 3.75 mm2; P = 0.0064). In conclusion in vivo neutralization of gastrin forms, which may potentially be fueling growth by an autocrine pathway, inhibited both primary growth and, to a greater degree, lung metastasis of a human colorectal tumour cell line. Immunization against tumour-associated gastrin forms may provide an effective therapy for advanced colorectal cancer.

Animals↗
PubMed1998

Gastric carcinoid expresses the gastrin autocrine pathway.

BACKGROUND: In gastric adenocarcinoma the gastrin autocrine-paracrine pathway is activated. As enterochromaffin-like (ECL) cells originate from the same stem as epithelial cells, the aim of this study was to determine if the gastrin autocrine pathway is present in gastric carcinoid. METHODS: Samples from ten patients with gastric carcinoid were assessed by immunocytochemistry using primary antibodies directed against gastrin precursors and the gastrin/cholecystokinin B receptor and detected using the avidin-biotin immunoperoxidase system. RESULTS: A high level of expression of precursor and mature gastrin peptides, together with the gastrin receptor, was seen in all carcinoids screened. CONCLUSION: In common with the glandular epithelium of the stomach the gastrin gene is activated during the neoplastic process in ECL cells. This finding may explain why some carcinoids do not regress after surgical procedures that lower serum gastrin. Antigastrin agents may be a useful treatment for carcinoid either in their own right or as an adjunct to surgery.

Adult↗
PubMed1993

Recurrent corneal infections in a patient with the acquired immunodeficiency syndrome.

A 29-year-old female intravenous drug abuser infected with the human immunodeficiency virus suffered recurrent, bilateral corneal infections over an 11-month period. Multiple infectious organisms were responsible, including capnocytophaga species, Candida albicans, Staphylococcus aureus, coagulase-negative staphylococcus, and a-streptococcus. One eye was eviscerated because of corneal perforation and loss of vision; the second eye has maintained good vision. Predisposing factors usually associated with corneal infections were absent. Treatment was complicated by extremely poor patient compliance, ongoing intravenous drug abuse, and concurrent multiple extraocular medical problems.

AIDS-Related Opportunistic Infections↗
PubMed1993

Flow cytometric studies of ploidy and proliferative indices in the Yorkshire trial of adjuvant progestogen treatment of endometrial cancer.

OBJECTIVE: To estimate whether flow cytometric indices provide independent measures of prognosis or predict response to prophylactic progestogens in endometrial cancer. DESIGN: Endometrial tumour specimens were retrieved and analysed by flow cytometry from 257 women who had been randomly allocated in a previous trial to receive prophylactic progestogen in addition to conventional therapy for endometrial carcinoma. SETTING: Fourteen district and two teaching hospitals in West Yorkshire. SUBJECTS: Women developing primary endometrial cancer between 1975 and 1983. MAIN OUTCOME MEASURES: Tumour ploidy status and proliferative indices and the relation of these to tumour stage and grade, to prognosis and to response to progestogens. RESULTS: Ploidy status and proliferative indices were related to tumour stage, grade and patient survival but were not independent predictors of survival. They did not predict patients who would respond to progestogens although there was a nonsignificant trend towards patients with diploid tumours surviving longer after progestogen treatment. CONCLUSIONS: Flow cytometry adds little to established prognostic indicators for endometrial cancer.

Aged↗
PubMed1989

The posterior pituitary regulates prolactin, but not adrenocorticotropin or gonadotropin, secretion in the sheep.

The aim of this study was to determine the role of the posterior pituitary gland in the control of PRL, LH, FSH, and ACTH secretion in sheep. Posterior pituitary function was removed in ovariectomized ewes by electrical lesioning of the hypothalamo-neurohypophysial tract immediately posterior to the stalk-median eminence (LESION); controls were subjected to sham surgery (SHAM). LESION caused a 2-fold increase in plasma PRL concentrations on days 1-3 after surgery. Thereafter, concentrations gradually declined until they were similar to those in SHAM ewes. There was no change in plasma concentrations of LH, FSH, or ACTH after LESION. Plasma PRL responses to insulin in SHAM ewes were completely abolished, and the plasma PRL response to chlorpromazine was reduced to almost half by LESION. In contrast, audiovisual stress (barking dog) and serotonin challenge caused an immediate release of PRL in both LESION and SHAM ewes, with the amplitude of the responses indistinguishable between groups. LESION had no effect on the plasma ACTH responses to audiovisual stress, insulin, or serotonin. We conclude that the posterior pituitary gland is involved in the regulation of PRL under some circumstances, but not of LH, FSH, or ACTH secretion in the sheep. Accordingly, changes in PRL release after hypothalamopituitary disconnection in this species may reflect a loss of posterior lobe function rather than the removal of hypothalamic inputs. In addition, the PRL response to insulin is dependent on a functional posterior pituitary gland, whereas responses to audiovisual stress and serotonin appear to rely on inputs to the pituitary gland via the median eminence and the long hypothalamo-hypophysial portal blood vessels.

Adrenocorticotropic Hormone↗
PubMed1989

Direct pituitary inhibition of prolactin secretion by dopamine and noradrenaline in sheep.

The effects of dopamine, noradrenaline and 3,4-dihydroxyphenylacetic acid (DOPAC) on the release of prolactin were examined in ovariectomized ewes. Infusion of dopamine (0.5 or 1 microgram/kg per min for 2 h i.v.) reduced plasma prolactin concentrations in a dose-dependent manner, whereas DOPAC (5 or 10 micrograms/kg per min for 2 h i.v.) had no effect. In a further series of experiments, ovariectomized hypothalamopituitary disconnected ewes were given dopamine or noradrenaline (each at 0.5 or 1 microgram/kg per min for 2 h i.v.), and both amines reduced mean plasma concentrations of prolactin with similar potency in a dose-dependent manner. These effects were blocked by treatment with pimozide and prazosin respectively. During the infusion of dopamine, the peripheral plasma concentrations of DOPAC and 3,4-dihydroxyphenylethyleneglycol (DHPG) were increased (DOPAC, 22 +/- 7 (S.E.M.) to 131 +/- 11 nmol/l; DHPG, 2.9 +/- 0.3 to 6.4 +/- 0.2 nmol/l), but plasma concentrations of dopamine and noradrenaline did not change. Finally, administration of domperidone, a specific dopamine receptor antagonist that does not cross the blood-brain barrier, resulted in a sustained increase in plasma prolactin concentrations in ovariectomized ewes. We conclude that the secretion of prolactin from the pituitary gland is under dual inhibitory regulation by both dopamine and noradrenaline in the sheep.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Effect and site of action of hypothalamic neuropeptides on prolactin release in sheep.

In an attempt to identify a physiological prolactin-releasing factor in the sheep, ovariectomized ewes were given intracarotid injections (10(-8)-10(-7) mol/animal) of thyrotropin-releasing hormone (TRH), vasoactive intestinal polypeptide (VIP), peptide histidine-isoleucine amide (PHI), oxytocin (OT), arginine vasopressin (AVP), substance P (SP), bombesin (BB), neurotensin (NT) and neuropeptide Y (NPY). Administration of TRH, AVP, NT and OT resulted in immediate and significant increases in plasma prolactin concentrations, the greatest stimulatory effect being obtained after TRH; other peptides had no effect in ovariectomized hypothalamo-pituitary intact ewes. AVP, NT and OT failed to release prolactin in ovariectomized ewes. These results suggest that (1) AVP, NT and OT may act via the hypothalamus to regulate prolactin secretion in hypothalamo-pituitary intact ewes; (2) VIP, PHI, SP, BB and NPY appear to have no direct roles at the pituitary level to control prolactin secretion in sheep, and (3) TRH stimulates prolactin secretion in ovariectomized ewes by a direct pituitary action.

Animals↗
PubMed1988

Gonadotropin-releasing hormone associated peptide (GAP) and putative processed GAP peptides do not release luteinizing hormone or follicle-stimulating hormone or inhibit prolactin secretion in the sheep.

A series of experiments was performed to monitor plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin responses to human gonadotropin-releasing hormone (GnRH) associated peptide (GAP) and related peptides. Ovariectomized hypothalamo-pituitary disconnected (HPD) ewes were challenged with injections (1-10 micrograms i.v.) of GAP, or given, with and without estradiol, hourly 500- or 1,000-ng pulses of GAP for 5-7 days. In all cases GAP failed to cause the release of LH or FSH from the pituitary gland or to alter mean plasma prolactin concentrations. When the same HPD ewes were given hourly or 2-hourly pulses of 250 ng GnRH, LH responded in a a pulsatile manner, and FSH secretion was maintained, thus confirming the functional integrity of the pituitary gland after HPD. Fragments of the GAP molecule (pro-GnRH 14-36, 28-36, 38-49, and 51-66) and GAP dimer did not stimulate LH or FSH or inhibit prolactin release in HPD ewes. GAP and GAP dimer did not affect pituitary responsiveness to GnRH administration. GAP also failed to inhibit the thyrotropin-releasing hormone-induced rise in prolactin. Finally, GAP injections (100 micrograms i.v.) given to lactating ewes did not cause any change in plasma prolactin concentrations. These data show that human GAP, GAP dimer, or putative processed GAP peptides do not act on the sheep pituitary gland in a variety of physiological states to regulate gonadotropin or prolactin secretion.

Animals↗
PubMed1987

An outbreak of serious Klebsiella infections related to food blenders.

An investigation, including environmental sampling, was undertaken after four leukaemic patients on the same hospital ward developed serious infections with Klebsiella aerogenes, capsular type K14. The source of this organism, common to all four patients, was found to be a food blender used for preparing milk-based drinks on the ward.

Aged↗
PubMed1987

Pattern of antibiotic and heavy-metal ion resistance in recent hospital isolates of Staphylococcus aureus.

Two hundred and one strains of Staphylococcus aureus isolated from in-patients and out-patients were examined for sensitivity to antibiotics, heavy-metal ions and ethidium bromide and for phage-typing pattern. Heavy-metal ion resistance was less frequent than reported in previous studies and was as frequent in penicillinase non-producing as producing strains. 'Methicillin-resistant' strains were resistance to ethidium bromide and mercury. Resistance to heavy-metal ions, including cadmium, may be becoming less common amongst clinical isolates of S. aureus.

Anti-Bacterial Agents↗