The Significance of Variceal Haemorrhage in Ghana: A Retrospective Review.

BACKGROUND: This study describes the burden of bleeding oesophageal varices at the main tertiary referral centre in Accra. DESIGN: Retrospective design to describe the endoscopic spectrum and review mortality data following acute upper gastro-intestinal bleeding at the Korle-Bu Teaching Hospital. Endoscopic data was reviewed in the Endoscopy Unit between 2007 and 2010. Mortality data was collated from the Department of Medicine between 2010 and 2013. INTERVENTIONS: The study questionnaire compiled clinical and demographic characteristics, endoscopic diagnoses, length of hospital admission and treatment regimens. MAIN OUTCOME MEASURES: Aetiology and time-trend analysis of mortality rates following acute upper gastro-intestinal bleeding; variceal bleeding treatment modalities. RESULTS: On review of the endoscopic diagnoses, gastro-oesophageal varices were identified in 21.9% of cases followed by gastritis 21.7%, duodenal ulcer, 17.0%, and gastric ulcer, 13.2%. Gastro-oesophageal varices were the predominant cause of death from acute upper gastro-intestinal haemorrhage from 46% in 2010 to 76% in 2013. Outcomes following acute upper gastro-intestinal bleeding were dismal with some 38% of fatalities occurring within the first 24 hours. Injection sclerotherapy was the dominant endoscopic modality for secondary prevention of variceal bleeding in comparison with band ligation, mainly as a result of cost and availability. CONCLUSIONS: At the tertiary centre in Accra, variceal bleeding is an increasingly common cause of acute upper gastro-intestinal haemorrhage in comparison with previous reviews in Ghana. Its significantly high in-hospital mortality reflects inadequate facilities to deal with this medical emergency. A strategic approach to care with endoscopic services equipped with all the necessary therapeutic interventions will be vital in improving the outcomes of variceal bleeding in Ghana.

Appropriateness and diagnostic yield of referrals for oesophagogastroduodenoscopy at the Korle Bu Teaching Hospital.

BACKGROUND: Increasing endoscopy workload in open-access services necessitates adoption of appropriateness criteria to check abuse and improve yield. OBJECTIVE: To assess the appropriateness of referrals for oesophagogastroduodenoscopy (OGD) and its relationship to yield at Korle-Bu Teaching Hospital (KBTH), Accra. METHODS: Referrals, signs, and symptoms of 375 consecutive patients for diagnostic oesophagogastroduodenoscopy were evaluated over four months. Indications were categorized as appropriate or inappropriate using the American Society of Gastrointestinal Endoscopy (ASGE) guidelines and endoscopic findings (yield) categorized as positive or negative. The relationship between these was analyzed and the diagnostic accuracy of the guidelines determined. RESULTS: There were 209 (55.7%) females, and 316 (84.3%) open-access procedures. Mean age was 46±17 years. Dyspepsia, 272 (72.5%) and epigastric tenderness, 192 (41.4 %) were the commonest symptom and sign respectively. Only 133 (35.5%) reported alarm symptoms. Appropriate referrals constituted 221(58.9%). Inappropriate referral rate was similar for endoscopists and non-endoscopists. Positive yield was 62.7%. Male sex, age > 45 years, haematemesis, persistent vomiting, gastroenterologists' referrals and epigastric tenderness were the best predictors of positive yield. Gastritis, 121 (32.3%), duodenal ulcer, 48 (12.5%) and oesophagitis, 36 (9.6%) were the leading endoscopy diagnoses. Carcinomas were reported only after 45 years and 18 (81.8%) of the cases had alarm symptoms. CONCLUSIONS: Inappropriate referral for OGD rate is high in Accra. Yield is improved by adherence to the ASGE guidelines but its accuracy as a screening tool for OGD at Korle- Bu Teaching Hospital is too low to recommend it for adoption.

Exacerbatory mechanism responsible for water immersion stress-induced gastric lesions in aged rats compared with young rats.

1. The present study was designed to investigate whether or not ageing affects the development of water immersion stress-induced gastric lesions in rats. Effects of cetraxate, an anti-ulcer drug, were also examined. 2. Gastric lesions were induced by 6 h water immersion stress in rats. Gastric mucosal blood flow was determined by the hydrogen gas clearance technique and nitric oxide synthase (NOS) activity was measured enzymatically. 3. Early development of gastric lesions was observed in aged rats and exacerbation of gastric lesions was also found. Lowering of gastric mucosal blood flow and reduced NOS activity were observed in aged rats. 4. Cetraxate mitigated the development of gastric lesions in young rats and also increased gastric mucosal blood flow and NOS activity. However, these favourable effects were diminished in aged rats. 5. Decreased NOS activity may be an important exacerbatory factor to the development of gastric lesions in aged rats. 6. Effects of cetraxate differed between young rats and aged rats. 7. These results may explain the refractoriness and drug resistance in gastric ulcers encountered by elderly individuals.

Hyperpolarization is not responsible for the acetylcholine-induced negative chronotropic action in the presence of isoproterenol.

It has been reported that acetylcholine hyperpolarizes the maximum diastolic potential of canine Purkinje fibers through a pathway involving a G protein and induces a decrease in their automaticity. It is unclear, however, whether the negative chronotropic action of acetylcholine in the presence of beta-adrenergic stimulation is due to the hyperpolarization of the maximum diastolic potential or a decrease in the slope of phase 4 depolarization. We used standard microelectrode techniques to study the negative chronotropic mechanism of acetylcholine in the presence of isoproterenol in adult canine Purkinje fibers. Fibers were incubated for 24 hours in Tyrode's solution alone (n = 10) or plus pertussis toxin (n = 10), and then superfused with acetylcholine (10(-9) to 10(-4) M) in the presence of isoproterenol (10(-7) M). Acetylcholine in the presence of isoproterenol significantly decreased automaticity without hyperpolarization of the maximum diastolic potential, and decreased the slope of phase 4 depolarization. The effects of acetylcholine on automaticity and the slope of phase 4 depolarization were attenuated by pertussis toxin. The present findings indicate that the negative chronotropic action of acetylcholine in the presence of isoproterenol is due to the decrease in the slope of phase 4 depolarization through a pathway involving a pertussis toxin-sensitive G protein and that it is not the result of hyperpolarization of the maximum diastolic potential.

Identification of compound heterozygous mutations (G188E/W382X) of lipoprotein lipase gene in a Japanese infant with hyperchylomicronemia: the G188E mutation was newly identified in Japanese.

We herein report a case of a 5-month-old Japanese female (patient AN) with fasting hyperchylomicronemia due to a primary lipoprotein lipase (LPL) deficiency. Patient AN was compound heterozygous for a missense mutation (GG818G-->GAG/Gly188-->Glu; G188E) in exon 5 and a nonsense mutation (TGG1401-->TGA/Trp382-->Stop; W382X) in exon 8 of the LPL gene. This resulted in less than 10% of the control levels for both the LPL activity and immunoreactive LPL mass in the postheparin plasma. A G188E mutation was thus identified for the first time in a Japanese, and the haplotype of this G188E allele was different from that of the G188E alleles identified in other ethnic groups. This additional mutation might be useful for early diagnosis of LPL gene aberrations in Japanese patients with fasting hyperchylomicronemia.

Effects of gamma-glutamylcysteine ethyl ester in cisplatin-induced changes in prostanoid concentrations in rat gastric and colonic mucosa.

We evaluated changes in gastric and colonic mucosal prostanoid contents in rats treated with cisplatin. We also determined effects of gamma-glutamylcysteine ethyl ester (GCE), a pro-drug of glutathione, on cisplatin-induced changes in prostanoid concentrations. Rats were divided into three groups--the control: 0.5 ml of physiological saline was administered intraperitoneally (i.p.); the cisplatin group: 0.5 ml of cisplatin, 10 mg/kg, was administered i.p.; the GCE + cisplatin group: GCE, 30 min before cisplatin injection. In each group, rat gastric and colonic mucosa were isolated and their prostanoid concentrations were determined using high-performance liquid chromatography. 6-Keto-PGF1 alpha, PGF2 alpha, PGE2 were detected in gastric mucosa. In addition to these prostaglandins (PGs), thromboxane (TX) B2 was also detected in the colonic mucosa. In the cisplatin group, gastric mucosal 6-keto-PGF1 alpha concentration decreased significantly 24 h after administration, while PGE2 and PGD2 concentrations were increased significantly after 12 and 24 h, respectively. In colonic mucosa, cisplatin increased PGE2 and PGD2 concentrations, while it decreased TXB2 concentration. 6-Keto-PGF1 alpha concentration was not affected by cisplatin in colonic mucosa. GCE canceled out these changes in prostanoid concentrations in both gastric and colonic mucosa. Changes in prostanoid concentrations might be implicated in the adverse gastrointestinal effects of cisplatin, and clinical application of GCE could be expected.

Implication of nitric oxide synthase activity in the genesis of water immersion stress-induced gastric lesions in rats: the protective effects of FK506.

BACKGROUND: Nitric oxide (NO) is a potent cytoprotective substance of gastric mucosa. FK506, an immunosuppressive drug, shows anti-gastric ulcer effects equivalent to famotidine, an H2 blocker, in rats. This study was designed to evaluate the cytoprotective mechanism of FK506 on gastric mucosa in relation to the changes in NO synthase activity. METHODS: Gastric lesions were induced in rats by water immersion stress. Changes in NO synthase activity during water immersion stress treatment, and effects of FK506 on NO synthase activity were determined enzymatically. Gastric mucosal interleukin (IL)-1 beta and IL-2 were measured by immunoradiometric assay. Gastric mucosal blood flow was measured by hydrogen gas clearance technique. RESULTS: FK506 mitigated gastric lesions developed by water immersion stress. Stress-induced lesions were exacerbated by NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, while sodium nitroprusside, a NO donor, mitigated the lesions. Water immersion stress increased NO synthase activity in the early phase (0.5 h after stress treatment) and decreased it in the late phase (6 h after). Decrease in NO synthase activity in the late phase was significantly mitigated by FK506, though it did not affect changes in NO synthase activity in the early phase. Water immersion stress increased gastric mucosal IL-1 beta and IL-2 contents 6 h after stress treatment, and these increases were prevented by FK506. FK506 itself did not affect gastric mucosal blood flow. L-NMMA treatment significantly decreased gastric mucosal blood flow. In contrast, gastric mucosal blood flow was significantly increased by sodium nitroprusside. CONCLUSIONS: Increase in NO synthase activity might contribute to cytoprotection, and a decrease in activity might be a harmful factor for the gastric mucosa. Preservation of NO synthase activity by FK506 might be involved in FK506's protective effects on the gastric mucosa.

Prevention of water immersion stress-induced gastric lesions through the enhancement of nitric oxide synthase activity in rats.

BACKGROUND: Gastric mucosal microcirculation is an important factor in the protection of gastric mucosa, and nitric oxide (NO) plays a crucial role in the regulation of regional blood flow. This study was designed to evaluate the effect of cetraxate, an anti-ulcer drug, on water immersion stress-induced gastric lesions in relation to the changes in NO synthase activity. METHODS: Gastric lesions were induced in rats by water immersion stress. The effects of cetraxate on NO synthase activity with or without stress was determined enzymatically. Changes in gastric mucosal prostaglandin (PG) contents with or without stress were also determined using high-performance liquid chromatography. Gastric mucosal blood flow was measured by hydrogen gas clearance technique. RESULTS: Water immersion stress-induced gastric lesions. Cetraxate significantly mitigated the lesions but N(G)-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO synthase, exacerbated the lesions. The favourable effect of cetraxate was remarkably diminished by administration of L-NMMA. NO synthase activity decreased significantly by 6 h after stress. Cetraxate treatment increased NO synthase activity throughout the experiment in rats with or without stress treatment. Water immersion stress decreased all PGs detected, i.e. 6-keto-PGF1alpha, PGF2alpha, PGE2 and PGD2. Cetraxate prevented stress-induced decreases in PG contents. L-NMMA showed no significant effect on PG contents. Cetraxate increased gastric mucosal blood flow significantly and L-NMMA cancelled out cetraxate-induced increase in blood flow. CONCLUSIONS: The pharmacological efficacy of anti-ulcer drugs such as cetraxate might be attributable to the enhancement of NO synthase activity resulting in an increase in gastric mucosal blood flow.

Usefulness of Scheimpflug photography to follow up Wilson's disease.

A 24-year old female with ocular changes (Kayser-Fleischer ring and sunflower cataract) indicating Wilson's disease was followed up from 9 years of age with anterior eye segment image documentation by Scheimpflug photography. A low copper diet and systemic D-penicillamine were administered after the initial diagnosis of Wilson's disease. During a 15-year follow-up period, the yellowish/brown-colored granular opacification on the anterior lens capsule and/or in the capsule has mostly disappeared and instead, the same type of opacification has emerged on the posterior lens capsule, showing rather progressive changes compared with the initial findings. These changes which had developed in the lens during the past 15 years were difficult to detect by slit lamp examination alone, but they were clearly revealed by Scheimpflug slit images. To our knowledge this is the first case report on ocular changes disclosed through the application of a newly developed anterior eye segment examination. Ergo, Scheimpflug photography is valuable for follow-up studies of ocular complications seen in patients with Wilson's disease.

[Family of hereditary elliptocytosis with abnormalities of spectrin function (Sp alpha 1/74)].

We have experienced a case of cytohemolytic hereditary elliptocytosis (HE) in a six-year-old boy. Metabolisms of the erythrocytic membrane were investigated on the members from his pedigree. The results were as follows; 1) The presence or absence of ovalocytic HE were studied in his pedigree. 2) Failure in the process of spectrin dimer to tetramer conversion was found. 3) Although abnormality existed in conversion of D to T by the patient's alpha-chain spectrin and normal beta-chain spectrin, no abnormality was recognized when normal alpha-chain and the patient's beta-chain were combined. 4) Decrease of the alpha-chain (80 kd) domain and appearance of abnormal (74 kd) spot were found by two dimensional peptide mapping of spectrin. 5) In his pedigree, neither patients with hereditary pyropoikilocytosis (HPP) nor carrier states were recognized. In summary, this patient's pedigree was considered to be HE [SP alpha 1/74]. This case appears to be the first case in Japan and only few cases have been reported in the world literature.

Cytogenetic effects of lead acetate on rat bone marrow cells.

The inducibility of chromosome aberrations and micronuclei by lead acetate was examined in vivo in bone marrow cells of rats after its single or repeated intraperitoneal administration. Lead acetate caused a small but significant increase in the frequencies of chromosomal aberrations (mostly chromatid gaps) and micronuclei. Chromatid breaks and acentric fragments were less frequent in occurrence. Complex aberrations such as chromatid exchanges and multiple breaks were never observed. Our findings suggest that lead acetate exerts a weak clastogenicity on rat bone marrow cells.

Measurement of lung density in congestive heart failure by computed tomography.

The computed tomography (CT) number within the region of interest (ROI) was used as a parameter to assess lung density in patients with congestive heart failure. Thirty-eight patients with valvular heart disease (VHD) and 34 patients with ischemic heart disease (IHD) were studied. Based on the New York Heart Association (NYHA) classification, 24 VHD patients were in class I or II (VHD I-II) and the other 14 were in NYHA class III or IV (VHD III-IV). Eighteen patients with IHD were in NYHA class I or II (IHD I-II) and 16 were in class III or IV (IHD III-IV). The CT number was measured bilaterally at the upper, middle and lower levels of the chest and compared with the corresponding values in 21 normal subjects (Group N). In a preliminary study on Group N, the CT numbers were insensitive to the size of the ROI, but were closely related to its location. In clinical applications, the mean values of the CT numbers in all six lung fields increased in the order of IHD I-II, to VHD I-II, IHD III-IV and VHD III-IV. Except for patients in IHD I-II, they were significantly larger than in Group N. The relationship between the CT number and the systolic and mean pulmonary arterial pressures and the pulmonary capillary wedge pressure were evaluated in 36 patients. Significant correlations were obtained in all six lung fields (r = 0.65-0.78, p less than 0.001). The results suggest that measurement of lung density by CT is useful for the quantitative evaluation of the severity of disease in patients with congestive heart failure.

Two-dimensional electrophoresis of plasma proteins without denaturing agents.

A technique of two-dimensional polyacrylamide gel electrophoresis for the separation of plasma proteins is described. Human plasma proteins were separated by isoelectric focusing followed by electrophoresis in a 4 to 21% linear gradient gel slab. No denaturing agent was used throughout the procedure, so that the analysis of native proteins is possible. Two-dimensional patterns obtained from normal human plasma samples were recorded as "staining density maps," which are similar to contour line maps, and more than 230 protein spots were counted reproducibly on each "staining density map." This technique permits the simultaneous estimation of pI's and approximate molecular weights of native proteins on the slab gel. Applications of this technique to an IgA myeloma plasma sample and a porcine serum sample are described.