Iron deficiency and anaemia in children with a high prevalence of haemoglobinopathies: implications for screening

BACKGROUND: Haemoglobin (Hb) concentration is used as a sole test for iron deficiency anaemia (IDA) in most developing countries since most anaemia is believed to be due to iron deficiency and confirmatory testing is generally unavailable. Yet the validity of this approach in regions where haemoglobinopathies are endemic has not been documented. METHODS: Haemoglobin and serum ferritin (SF) were measured in 559 Northern Thai children aged 6 months to 13 years of age. The sensitivity of SF to identify iron deficiency was also assessed in a subsample of children with low or low-normal Hb and normal SF by testing the Hb response to a trial of oral iron. RESULTS: While anaemia was common (27%), IDA constituted 19% and none of all anaemia in preschool and school age children, respectively (P < 0.002). Iron depletion was similarly more prevalent in younger children (P < 0.002). Children with IDA were younger (P < 0.001) and the anaemia more severe (P < 0.0001) compared to those with non-IDA. Of anaemic children with normal SF values who received a therapeutic trial of iron, only 6% responded with an increase in Hb of > or = 1 g/dl. CONCLUSIONS: For populations such as ours most anaemia is not due to iron deficiency and a single Hb determination is therefore not acceptable for a presumptive diagnosis of IDA.     

Chronic coronary pseudoaneurysm after stent implantation

A 14-year-old boy presented with anorexia and weakness whereon the diagnosis of dimorphic anaemia was made. An excellent response to iron and vitamin B12 was observed. In addition, the patient had non-obstructive hypertrophic cardiomyopathy. At endoscopy 2.5 years later, an adenocarcinoma was diagnosed and the patient underwent a high subtotal gastrectomy. To the best of our knowledge, this rare association has never been reported in children. CONCLUSION: We report a youngster with pernicious anaemia, associated with nonobstructive hypertrophic cardiomyopathy in whom gastric adenocarcinoma was found. Patients with pernicious anaemia are at greater risk of developing gastric carcinoma than the general population, therefore we recommend routine periodic gastroscopic surveillance in the paediatric population with pernicious anaemia.     

Is age a limiting factor for carotid surgery?

To evaluate the role of carotid surgery in elderly patients 75 years and older, we reviewed 912 carotid endarterectomies performed on 806 patients between 1987 and 1990. There were 151 patients (19% of the whole series) aged 75 years and older (160 endarterectomies, group A), including 29 octogenarians, vs 655 patients under 75 years of age (group B). There were more women in the elderly age group (44%) than in the younger one (38%). Symptoms, risk factors, operative outcome and follow up data of the two groups were compared. The risk profile was similar for the two age groups, with exception for coronary heart disease, less frequent in the older patient group (25% had previous infarction vs 44%). Indication for carotid endarterectomy was different in the two age groups: 41% of group A underwent prophylactic thrombendarterectomy for high degree stenosis, while only 30% of group B had asymptomatic carotid disease. In group A, 6% of the patients had carotid endarterectomy after recovering from a mild stroke, vs 2% in group B. Angiography revealed bilateral carotid disease in 59% of the group A patients (including 15% with contralateral occlusion) vs 40% in group B. Operative mortality was 1.5% for the younger age group vs 2.5% for the older age group. The cause of death was cardiac in 60%. A follow up is available for all patients who benefited carotid endarterectomy since 1976, including 180 patients aged 75 years or older.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nursing informatics--what on earth?

AIM AND BACKGROUND: Two forms of hypochromic microcytic anaemia i.e. iron deficiency and beta-thalassaemia trait are common in our society. This study reports the prevalence of iron deficiency anaemia and beta-thalassaemia trait and predictive value of MCV/RBC count ratio to discriminate between two. METHODS: Venous blood was taken from 299 students of Karachi Medical & Dental College and Ziauddin Medical University in Na2 EDTA and analyzed by semi-automated Sysmex K-1000 haematology analyzer. MCV/RBC count ratio was used to discriminate between iron deficiency and beta-thalassaemia trait and > 14% was marked as iron deficiency. Hb electrophoresis was used as gold standard test for confirmation. Serum iron and TIBC was performed to confirm iron deficiency anaemia. RESULTS: Iron deficiency was found in 9% while beta-thalassaemia was seen in 3% students. MCV/RBC count ratio showed a positive predictive value of 91%. CONCLUSIONS: In areas where iron deficiency anaemia and beta-thalassaemia trait are common, MCV/RBC count ratio can be used to screen out beta-thalassaemia trait.     

The danger of B12 deficiency in the elderly

Vitamin B12 deficiency damages nerve cells and aggravates nervous system disorders even in the absence of evidence of anaemia. Prevalence of B12 deficiency increases with age especially over 65 and is frequently associated with Alzheimer's disease. Recent American surveys record a higher prevalence of B12 deficiency and of undiagnosed and untreated pernicious anaemia in the elderly than reported earlier. B12 deficiency is also reported to be a risk factor for heart disease, stroke and accelerated ageing.     

Changes in erythroblast morphology as an index of response to cyanocobalamin in patients with megaloblastic anaemia

Fifty-three patients with megaloblastic anaemia treated with cyanocobalamin and folic acid have been studied. Repeat marrow examination was found to be of value in assessing response to treatment. The early improvement in marrow morphology in patients with pernicious anaemia was greater with 1000 mug than with 5 mug doses of cyanocobalamin. The effect of folate deficiency in delaying marrow response to cyanocobalamin in patients with pernicious anaemia is described and combined cyanocobalamin and folic acid treatment was found to be more effective than either alone. The response to large doses of cyanocobalamin in folate deficient patients was unrelated to the initial serum vitamin B12 level.     

A Chinese patient with pernicious anemia; a medical experience from the Indonesian period

On May 19th 1952 a 64-year-old Chinese man was admitted to a hospital at Yogyakarta (Indonesia) on account of a sawing noise in both ears and some soreness of the tongue. He had macrocytic anemia (haemoglobin: 3.7 mmol/l) and the tongue showed some smooth patches. A presumptive diagnosis of pernicious anaemia was confirmed by gastric analysis which revealed a histamine fast achlorhydria. On treatment with vitamin B12 the noise in the ears rapidly disappeared and there was a characteristic rise in reticulocytes and haemoglobin content. After 3 years the patient died of inoperable gastric carcinoma. There probably was a hereditary component as in a 54-year-old cousin, who also suffered (and died) from gastric carcinoma, gastric analysis showed a histamine fast achlorhydria. The patient is the first case of pernicious anaemia described in a Chinese resident of Indonesia. A survey of the literature revealed that until now pernicious anaemia has been recorded in 31 Chinese patients, in chronological order from the following countries: U.S (1945), Indonesia (1954), Singapore (1967), Hong-Kong (1969) and China (1990). In the autochthonous Chinese population no case has yet been reported.     

Prophylactic iron supplementation after Roux-en-Y gastric bypass: a prospective, double-blind, randomized study

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Roux-en-Y gastric bypass. DESIGN: Prospective, double-blind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after Roux-en-Y gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6-month intervals postoperatively in 56 menstruating women who had Roux-en-Y gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebo-treated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebo-treated than iron-treated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after Roux-en-Y gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have Roux-en-Y gastric bypass.     

Autoimmune polyglandular failure associated with malabsorption and gastric carcinoid tumour

A 21-year-old female with autoimmune polyglandular failure (APG) manifested by insulin-dependent diabetes mellitus (IDDM), hypothyroidism and pernicious anaemia developed severe malabsorption due to exocrine pancreatic insufficiency. Supplemental pancreatic enzymes resulted in marked improvement of steatorrhea. There was also an incidental finding of gastric carcinoid tumour. We identified only 13 other patients in our institution with either type 2 or 3 APG, one of which had significant steatorrhoea. Another patient with IDDM, hypothyroidism and pernicious anaemia had an asymptomatic gastric carcinoid tumour. The possible mechanisms for malabsorption in APG are discussed.     

Kinetic diversity in the fusion of exocytotic vesicles

Age is the most important factor for the durability of biological valves. With an original design the Carpentier-Edwards pericardial valve showed improved results at 10 years. The influence of age on valve related complications is studied with a 10 year follow up on 807 valvular replacements. METHODS: Between January 1984 and December 1993, 807 patients underwent valve replacements with a Carpentier-Edwards pericardial bioprosthesis. Patients, 193 were younger than 60 years, 284 between 60 and 70 years and 330 patients were older than 70 years. All patients but seven were followed up for an average of 4.18 years after their operation and total follow up was 3373 patient years. Patients were divided into three groups of age: group I, less than 60 years; group II, 60-70 years; group III, over 70 years. A retrospective comparison was made between age groups. RESULTS: At 11 years, valve related complications included 97 patients with 27 valve related deaths. Rates of valve related death increase with age linearized rate were 0.3, 0.6 and 1.2%, respectively. No difference was observed for rates of all valve related morbidity: 2.6, 2.4 and 3.5%, respectively. Risk of thromboembolism increased with age, linearized rates were: 0.3, 0.7 and 1.3%. Risk of deterioration and reoperation decreased with age, rates of deterioration were 0.8, 0.1 and 0%. Other valve related events had the same incidence in all groups. No statistical difference was observed between group II and group III for deteriorations and reoperations. CONCLUSIONS: The performance of the Carpentier-Edwards pericardial valve is the same at 10 years in group II and III. This study supports the clinical use of this tissue valve in patients over 60 years. The results in group I are satisfactory, nevertheless, a more durable biological valve is needed for young patients.     

Aortic valve replacement in the elderly. Encouraging postoperative clinical and hemodynamic results

Seventy-three patients aged 60 and over and 277 patients under 60 years of age underwent isolated aortic valve replacement (AVR) for aortic stenosis, regurgitation, and mixed disease from 1966 through 1975. Cardiac catheterization was performed five to nine months following operation in 77% of these patients. Follow-up averaged 55 months per patient. The hospital mortality in the elderly group was 2.7%, compared to 5.8% in the younger group. The late cardiac mortality was 21% and 19%, respectively. There was significant improvement (P less than .001) in the left ventricular end-diastolic pressure, cardiac index, and functional class in each of the three disease groups in the younger as well as the elderly patients. More important, the magnitude of improvement in each of these variables in patients over and under 60 years of age was not significantly different. Increasing longevity will make cardiac operations more common in the older population. These findings indicate that AVR carries the same low risk and brings about a similar improvement in left ventricular pump function in patients older and younger than 60.     

Surgical clips: a cause of late recurrent gallstones

BACKGROUND: Oral iron supplements, which are usually in the form of ferrous (Fe2+) salts, are toxic to the gastrointestinal mucosa, and so intolerance is common, resulting in poor compliance and failure of treatment. The sugar derivative maltol strongly chelates iron, rendering it available for absorption and stabilized in the less toxic ferric (Fe3+) form. AIM: To test whether ferric trimaltol could correct iron deficiency anaemia in patients intolerant of ferrous sulphate. METHODS: Twenty-three patients were recruited from gastroenterology clinics, of whom 1 5 had inflammatory bowel disease, a group often difficult to treat with oral iron. Patients with iron deficiency anaemia and documented intolerance to ferrous sulphate were given 3 months of treatment with ferric trimaltol. RESULTS: Nineteen of 23 patients completed the treatment and anaemia was fully corrected in 14 of these, mean haemoglobin increased from 106 +/- 15 to 126 +/- 16 g/L, and there was a particularly low incidence of side-effects. Of 11 patients with inflammatory bowel disease who completed the study, nine fully corrected their anaemia. CONCLUSION: The results demonstrate that in patients intolerant of ferrous compounds, ferric trimaltol corrects iron deficiency and has a low incidence of side-effects.     

Work time estimates for ophthalmic diagnoses and procedures. Results from the Eye Care Workforce Study

OBJECTIVE: To compare the clinical presentation, time elapsed to diagnosis, and survival of elderly patients (> or = 65 years) with that in younger patients with malignant primary brain tumors. DESIGN: Retrospective cohort study. SETTING: Four hospitals in Minneapolis, Minn. PATIENTS: Seven hundred fourteen patients diagnosed as having and treated for primary malignant brain tumors between 1980 and 1995; 230 (32%) were 65 years or older. MAIN OUTCOME MEASURES: The type and duration of the chief presenting symptom, the time elapsed to diagnosis, the treatment modalities used, and patient survival were analyzed. RESULTS: Time elapsed from onset of symptom to diagnosis was not longer for elderly patients than younger ones, with the exception of patients aged 18 to 24 years, who had a significantly longer delay in diagnosis (P = .004). Elderly patients were significantly less likely to present with headache or seizure (P<.001), and more likely to present with confusion, aphasia, or memory loss (for each, P<.001). With the single exception of confusion, the duration of all other presenting symptoms was not significantly longer for patients 65 years and older compared with younger patients. Survival is significantly reduced in older patients, and appears to worsen significantly in patients 45 years and older (P<.001). A significantly higher proportion of patients 65 years and older with glioblastoma multiforme received no treatment (P = .004) if diagnosed after 1990. CONCLUSIONS: Elderly patients (> or = 65 years) with malignant brain tumors are diagnosed as promptly as younger patients, although they have a markedly different constellation of symptoms. Since diagnosis of brain tumors continues to improve in the elderly, it may be more difficult to ascribe the steady increase in incidence to artifactual factors.     

LDH isoenzymes and gastrin in achlorhydri (author's transl)

Several haematological findings (especially the values of serum LDH and its isoenzymes) were compared with changes in the gastrin level in pernicious anaemia. While vitamin B12 substitution therapy led to normalization of the anaemia and of the enzyme levels, gastric atrophy and, hence, the elevation in serum gastrin levels remained unchanged. Determination of serum gastrin, therefore, provides a valuable tool for the verification of the diagnosis of pernicious anaemia in treated cases.     

Surgery in elderly patients with otosclerosis

Hearing results and complications of surgery were studied in 42 patients with otosclerosis (46 ears operated on) who were over the age of 60 years at the time of stapedectomy. The mean follow-up period was 8 years. The results were compared with those obtained in 275 patients (330 ears operated on) younger than 60 years of age undergoing stapes surgery during the same time period. Large fenestra stapedectomy with fascia seal to the oval window was used in all cases. Hearing results as judged by postoperative air-bone gaps were as good in the older age group as in the younger patients. In contrast to some earlier reports, complications of surgery such as postoperative sensorineural hearing loss occurred not more frequently among elderly patients than in younger patients. It is concluded that stapes surgery should be offered to elderly patients with the same indications as in younger patients with otosclerosis.     

Favorable results of implantable cardioverter-defibrillator implantation in patients older than 70 years

BACKGROUND: The clinical results of implantable cardioverter-defibrillator (ICD) implantation in the elderly have received limited documentation. As the longevity of the U.S. population has increased, so has the need for ICD implantation in the elderly. We evaluated the efficacy and outcome of ICD implantation in elderly patients (>70 years) compared with younger patients. METHODS: The case records of all consecutive patients who underwent ICD implantation at our institution between 1986 and 1994 were reviewed. Of a total of 238 patients, 78 patients were 70 years of age or older and 160 patients were younger than 70 years of age. RESULTS: The mean age of the younger group was 58 years and that of the elderly group was 74 years. There were no statistical differences in the presence of coronary artery disease, left ventricular systolic function, the inducibility of arrhythmias, or the history of sudden cardiac death. The hospital morbidity rate was similar in both groups (6.9% in the younger group and 7.7% in the elderly group; p = not significant). The operative mortality rate was 1.9% for the younger group and 1.3% for the elderly group (p = not significant). At a mean follow-up of 33 +/- 26 months, Kaplan-Meier survival curves demonstrated similar survival rates, with 93%, 82%, and 65% of the patients alive at 1, 3, and 6 years, respectively. CONCLUSIONS: Implantable cardioverter-defibrillator implantation was equally effective in the treatment of patients older than 70 years as in younger patients. No differences in theoretic survival or morbidity were observed.     

Care of wounds today

Fifty three (45 males, 8 females) patients with primary meylodysplastic syndrome were seen between January 1990 and June, 1996. Fifteen (28%) patients had refractory anaemia (RA), 9 (17%) refractory anaemia with ring sideroblast (RARS), 21 (40%) refractory anaemia with excess blasts (RAEB), 5 (9%) refractory anaemia with excess blasts in transformation (REABt) and 3 (6%) had chronic myelomonocytic leukemia (CMML). The mean age for the whole cohort was 59 years. Patients with RAEB and RAEBt were significantly younger than other FAB types with a mean age of 53.5 and 45 years respectively. Among the FAB types RAEB appeared to be over represented. Symptomatic anaemia (66% cases) was the major cause to seek medical attention. The commonest laboratory findings was anaemia; Hb < 8 g/dl in 31 (59%) patients. Only two patients had Hb > 12 g/dl at presentation. Twenty four (45%) patients had normocytic anaemia, mainly in RAEB group (61%). Macrocytosis was a dominant finding in patients with RA (53%) and RARS (53%). Bicytopenia (72%) was a more common finding than pancytopenia (8%). Bone marrow was normocellular in 32 (60%) patients and hypoplastic in 11 (21%). Dyserythropoiesis predominantly affected RA (80%), RARS (55%) and RAEB (43%) groups. Bilineage dysplasia (21%) was commoner than trilineage dysplasia (19%). Increased bone marrow fibrosis was seen in about half of the available trephines, mainly in RAEB patients. Median survival of patients was ten months with a follow up duration of 2-55 months. Four patients transformed to acute leukemia (M1 or M2) and died subsequently. However, infection was major complication and cause of death (10 cases). The preponderance of younger people to acquire the disease (especially the RAEB and RAEBt variants), the emergence of RAEB as the major group of MDS and increased prevalence of hypoplastic MDS point towards non-therapeutic genotoxin (s) in the causation of disease. Shortened survival and low rate of acute transformation points that patients did not withstand cytopenias and died earlier.     

Anisocytosis and the C-1000 Channelyzer in macrocytic anaemia

Red cell anisocytosis as assessed using the Coulter Channelyzer C-1000 showed an increase with progressive anaemia in 25 patients with macrocytosis due to B12 and/or folate deficiency. In deficiency of a single factor, the degree of anisocytosis increased with progressive anaemia. In five cases with B12 and folate deficiency combined, anisocytosis was markedly increased out of proportion to the degree of anaemia present. Iron stores were also reduced in four of these cases. It is suggested that objective measurement of anisocytosis is of early diagnostic value in the assessment of multiple haematinic factor deficiency, for example, in macrocytic anaemia associated with malabsorption states and unexpected multiple deficiency states.     

Calcium antagonists in the elderly. A risk-benefit analysis

Calcium antagonists are effective in lowering blood pressure, relieving anginal symptoms and improving exercise tolerance in older and younger patients with coronary artery disease. Verapamil and diltiazem are effective in slowing ventricular response rates to supraventricular arrhythmias in both older and younger patients. Although they belong to at least 3 distinct chemical classes, a moderate decrease in the clearance of all calcium antagonists occurs with aging. Most clinical trials of these drugs have used the same dosages in older and younger patients, confounding analyses of sensitivity in older compared with younger patients. Greater reductions in blood pressure usually occur in older compared with younger patients receiving the same dosages of calcium antagonists; similarly, the dosage required to reduce blood pressure to a certain level is usually lower in older compared with younger patients. Drug acquisition costs are generally higher for calcium antagonists than for beta-blockers or diuretics. Compared with younger patients, greater heart rate suppression may be seen in older patients treated with verapamil and diltiazem; conversely, heart rate increases are usually seen with dihydropyridines. Calcium antagonists have not been shown to provide long-term benefits or decreased morbidity or mortality in elderly patients with hypertension. Verapamil, but not dihydropyridines, decreases mortality after myocardial infarction in patients without congestive heart failure. Calcium antagonists have not been shown to be beneficial in the treatment of acute stroke. Adverse effects, such as a postural hypotension, may be more frequent in elderly compared with younger patients. In addition, the elderly are at greater risk for drug interactions with calcium antagonists due to the higher likelihood that they are receiving other drugs.     

A single point mutation controls the cholesterol dependence of Semliki Forest virus entry and exit

Hypergastrinaemia-associated changes of non-antral argyrophil cells in man are of increasing interest, because of the development of potent inhibitors of gastric acid secretion. Using an antibody against chromogranin A, we identified micronodular endocrine cell hyperplasia of the oxyntic mucosa in gastric biopsy specimens of patients with hypergastrinaemia of different backgrounds. Consecutive ultrathin sections were examined at the electron-microscopical level. Endocrine cell types within the (extraepithelial) micronodules closely resembled those in the adjacent mucosa. Micronodules were classified into two groups. The first group was composed of endocrine cells only and predominated in patients with drug-induced hypergastrinaemia and/or chronic gastritis, and in a gastrinoma/MEN I patient. The second group represented "neuroendocrine complexes", showing a close intermingling of non-myelinated nerve fibres with endocrine cells, and was found predominantly in pernicious anaemia. Micronodular argyrophil cell growth in man is therefore heterogeneous and depends on the background of the hypergastrinaemia.