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Biomedical subjects

T Hongo

Publications and source records attributed to T Hongo.

At least 37 records · Page 2Linked to original sources

The effect of oral clonidine premedication on lumbar cerebrospinal fluid pressure in humans.

Alpha-2 adrenergic agonists including clonidine decrease cerebral blood flow. The specific actions of clonidine on cerebrospinal fluid (CSF) pressure in humans remain to be elucidated. We evaluated the effect of oral clonidine premedication on lumbar CSF pressure in patients without intracranial disease. Seventy-four patients undergoing subarachnoidal block were divided randomly into either a clonidine or a control group. In the clonidine group, the patients were premedicated orally with 5 microg/kg clonidine 60 min before arrival in the operating room. Subarachnoidal puncture was performed via midline approach using a 23-gauge needle at the L2-3 or L3-4 intervertebral space with the patient in the lateral decubitus position. Before the injection of local anesthetic, lumbar CSF pressure was measured. Lumbar CSF pressure was 8.1+/-2.4 mmHg in the clonidine group, which was significantly lower than that in the control group (9.4+/-2.8 mmHg, p<0.05). The cerebral perfusion pressures were 76.2+/-12.5 mmHg in the clonidine group and 91.7+/- 15.4 mmHg in the control group (p<0.001). In the clonidine group, preanesthetic mean blood pressure had a significant correlation with lumbar CSF pressure (r=0.619, p=0.019). We conclude that Lumbar CSF pressure was attenuated by oral premedication with 5 microg/kg clonidine. Clonidine also contributed to a significant correlation between preanesthetic mean blood pressure and CSF pressure.

Administration, Oral↗

[Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents].

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.

Bacteria↗

[Activities of antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. Levofloxacin--Surveillance Group].

The surveillance study was conducted to determine the antimicrobial activity of fluoroquinolones (ofloxacin, levofloxacin, ciprofloxacin, tosufloxacin) and other 20 antimicrobial agents against 5,180 clinical isolates obtained from 26 medical institutions during 1998 in Japan. The resistance to fluoroquinolones was remarkable in Enterococci, methicillin-resistant staphylococci and Pseudomonas aeruginosa from UTI. However, many of the common pathogens such as Streptococcus pneumoniae including penicillin-resistant isolates, methicillin-susceptible Stahylococcus aureus, Moraxella catarrhalis, the family of Enterobacteriaceae, Haemophilus influenzae including ampicillin-resistant isolates have been kept to be susceptible to fluoroquinolones. About 90% of P. aeruginosa isolates from RTI were susceptible to fluoroquinolones. In conclusion, the results from this surveillance study suggest that fluoroquinolones are useful in the treatment of various bacterial infections including respiratory infections.

Anti-Infective Agents↗

Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia.

We investigated the alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia (T-ALL) and T-ALL cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Mutations of the p53 gene were found in three of 57 (5%) patients at diagnosis, one of 14 (7%) patients at relapse and in 12 of 18 (67%) cell lines. In these 12 cell lines, four had more than two mutations of the p53 gene. The p53 mutations were found in four of five cell lines whose original fresh leukemic cells were simultaneously examined original fresh leukemic cells. However, only one of the four fresh leukemic cells had the same mutation. All patients with p53 mutations in the course of disease died. Mutations of the p21 gene were not identified in 71 fresh samples and in 18 cell lines. N-RAS mutations were found in two of 57 (4%) fresh T-ALL patients at diagnosis, and four of 18 cell lines (22%), whereas no mutations were detected in any samples at relapse. Alterations of the p16 gene were found in 18 of 47 (38%) patients at diagnosis and in seven of 14 (50%) at relapse. These differences were not statistically significant. There were no differences in the frequency of alteration of the p16 and p15 genes between event-free patients and the remaining patients. Furthermore, we found the methylation of p16 gene in three of seven patients lacking homozygous deletions, suggesting higher frequency of p16 inactivation than previous reports in T-ALL. Interestingly, we found that one allele is inactivated by methylation and another allele had nonsense mutation in one cell line (KOPT-KI), resulting in loss of protein expression of p16. This type of p16 inactivation has not been so far reported in leukemia. We conclude that, (1) p53 mutations are infrequent at diagnosis but tend to be associated with poor clinical outcome; (2) RAS and p21 mutations may not be involved in the pathogenesis of T-ALL; (3) not only frequent alterations of p16 and p15 genes but also methylation of p16 gene are involved in initiating the leukemogenesis of T-ALLs, and (4) these 5 genes are independently involved in T-ALL.

Adolescent↗

A randomised dose-comparison trial of granisetron in preventing emesis in children with leukaemia receiving emetogenic chemotherapy.

This randomised study was performed to assess the anti-emetic efficacy and tolerability of two-dose regimens of granisetron in children with leukaemia. 49 children with leukaemia were treated with three consecutive courses of high-dose methotrexate or cytarabine regimen. During the first course, patients were evaluated regarding the emetogenicity of each regimen. They were randomised in a crossover manner to receive 20 or 40 micrograms/kg of granisetron before the second and third course of chemotherapy. Neither emesis nor severe appetite loss were observed in over 80% of patients within the first 24 h in all treatment groups. There was no significant difference in the anti-emetic efficacy between the two-dose regimens of granisetron. However, complete protection was achieved less frequently on days 2 and 3. Older children and girls appeared to be less well protected. No adverse events attributable to granisetron were observed. Granisetron dose regimens of 20 and 40 micrograms/kg are, comparably, well tolerated and effective in controlling chemotherapy-induced emesis in the first 24 h, though this protection fails thereafter, particularly in older patients and girls.

Adolescent↗

Abnormally large evoked potentials arising from dorsal column fibers in the region of chronically compressed spinal cord.

OBJECTIVE: To understand the origin and mechanism of the large evoked potentials known to occur in chronically compressed spinal cord. METHODS: Electrophysiological analysis was made of evoked potentials produced in the cervical cord compressed for more than 1 year by rotating a screw in the vertebral body, in 4 adult cats. RESULTS: In all cats, manifesting no motor disturbance, large positive or negative evoked potentials were recorded from the cord dorsum at the compressed region following lumbar cord stimulation. These potentials followed high-frequency stimulation and were judged as conducting volleys of directly activated fibers. Intraspinally, single fiber spikes, normally barely recordable with the glass microelectrodes, were recorded extracellularly from localized areas within the dorsal column restricted to the compressed region. Such single fibers showed slowed conduction at the compressed region without a conduction block. Histologically, demyelinated fibers were observed in localized areas in the dorsal column of the compressed region. CONCLUSION: We concluded that the large abnormal surface potentials originated from the dorsal column and were attributed to an increase in action current in affected fibers, which presumably occurred associated with demyelination.

Animals↗

Functional expression of Fas and Fas ligand on human intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IEL) constitute the first lymphoid compartment to encounter dietary antigens and intestinal pathogens. IEL are proposed to be involved in the defence against bacterial and viral invasion and to play an important role in mucosal immunity. Fas (CD95/APO-1) is a surface receptor that induces apoptotic cell death upon ligation with Fas ligand (FasL). The aim of this study was to examine the expression and function of Fas and FasL on freshly isolated normal human colonic IEL. The expression and function of Fas and FasL on IEL isolated from 40 normal colonic specimens were examined by flow cytometry, reverse transcriptase-polymerase chain reaction, immunohistochemistry, and DNA-release cytotoxicity assay. Virtually all CD3+ IEL (95.2 +/- 4.3%) expressed Fas and were sensitive to agonistic anti-Fas antibody, whereas only 56.6 +/- 8.4% of peripheral T lymphocytes expressed Fas and were resistant to the antibody. We also detected FasL mRNA and protein (40.1 +/- 4.2%) on IEL, and found that IEL exerted FasL-mediated cytotoxicity against Fas-expressing target cells. These findings suggest that human IEL are activated in situ but are tightly regulated by the constitutive expression of functional Fas and FasL to maintain homeostasis of the mucosal immune system.

Adult↗

[Vibrio vulnificus infection: clinical and bacteriological analysis of four cases].

Vibrio vulnificus (V. vulnificus) infection has recently been drawing attention as a high mortality disease especially in a patient with the preexisting chronic liver disease. The illness caused by V. vulnificus is divided into three groups such as primary septicemia, wound infection and gastrointestinal illness. Primary septicemia, which is the most common in Japan, is defined as a systemic illness presenting fever or hypotension with recovery of V. vulnificus from blood or tissue without the apparent primary focus of infection. We diagnosed four cases as infectious diseases of V. vulnificus by isolating it from each clinical material in Kurashiki Central Hospital from 1984 through 1997. We investigated clinical manifestations of the four cases including season of the onset, presence of drinking habit, underlying diseases, consumption of raw seafood, symptoms, presence of disseminated intravascular coagulation (DIC) or shock, laboratory data, administered antibiotics and the outcomes of the treatment. And for each strain, we also performed in vitro drug susceptibility tests. The age of the patients ranged from 49 to 61 years old (mean 56), and all of the patients were male. Each of them had a chronic liver disease as an underlying disease. Two of them had a history of raw seafood consumption prior to the onset of the illness. Skin manifestations appeared in two of the four patients. All the patients complicated septic shock and DIC. V. vulnificus was isolated from the venous blood cultures of them. Three of the four were given a diagnosis of primary septicemia and one was made a diagnosis of acute cholecystitis which has never been reported previously. Three of the four patients died and only the rest was alive as a result of antimicrobial therapy. In the sensitivity tests, the four strains were revealed to be very sensitive to the antimicrobials such as minocycline, cephalosporins of the third generation and carbapenems. Once patients with a chronic liver disease are infected with V. vulnificus, their prognosis is poor. Every effort should be made to advise not to have uncooked seafood. Physicians should be informed about the characteristics of the disease caused by this bacteria and treat any suspicious case promptly and appropriately.

Bacteriological Techniques↗

Tandem duplication of the FLT3 gene is found in acute lymphoblastic leukaemia as well as acute myeloid leukaemia but not in myelodysplastic syndrome or juvenile chronic myelogenous leukaemia in children.

We examined mRNA expression and internal tandem duplication of the Fms-like tyrosine kinase 3 (FLT3) gene in haematological malignancies by reverse transcriptase-polymerase chain reaction (RT-PCR) and genomic PCR followed by sequencing. By RT-PCR, expression of FLT3 was detected in 45/74 (61%) leukaemia cell lines and the frequency of expression of FLT3 was significantly higher in undifferentiated type (B-precursor acute lymphoblastic leukaemia; ALL) than in differentiated type cell lines (B-ALL) (P = 0.0076). Using the genomic PCR method, 194 fresh samples including 87 acute myeloid leukaemias, 60 ALLs, 32 myelodysplastic syndromes (MDSs) and 15 juvenile chronic myelogenous leukaemias (JCMLs) were examined. Tandem duplication was found in 12 (13.8%) AMLs and two (3.3%) ALLs. Sequence analyses of the 14 samples with the duplication revealed that eight showed a simple tandem duplication and six a tandem duplication with insertion. Most of these tandem duplications occurred within exon 11, and two duplications occurred from exon 11 to intron 11 and exon 12. No tandem duplications of FLT3 gene were detected in MDS or JCML. The frequency of tandem duplication of FLT3 gene in childhood AML was lower than that in adult AML so far reported. All of the 12 AML patients with the duplication died within 47 months after diagnosis, whereas two ALL patients with the duplication have survived 44 and 72 months, respectively. These two ALL patients expressed both lymphoid and myeloid antigens and were considered to have biphenotypic leukaemia. These results suggest that tandem duplication is involved in ALL in addition to AML, but not in childhood MDS or JCML, and that childhood AML patients with the tandem duplication have a poor prognosis.

Acute Disease↗

[Survey of the sensitivities of clinical isolates to antibacterial agents (annual report)].

Research groups were formed in 21 institutions nationwide to investigate carbapenem resistance. The activities of various antibacterial agents, principally carbapenems, were tested against clinical isolates collected from these institutions. The broth microdilution method was used to determine the minimum inhibitory concentrations (MIC) of 17 antibacterial agents for 1,241 strains of 11 bacterial species isolated at all institutions between October and December 1996. The results were as follows: Carbapenems exhibited strong antibacterial activities against MSSA and Streptococcus pneumoniae and showed low activities against MRSA. Their activities against Enterococcus faecalis were comparable to that of ampicillin and piperacillin. The carbapenems showed high activities against Haemophilis influenzae, Escherichia coli, Klebsiella pneumoniae. Enterobacter cloacae. Serratia marcescens and Bacteroides fragilis group. Their activities were greater than that exhibited by other beta-lactam antibacterial agents, but some resistant strains of Serratia marcescens were detected. The antibacterial activity of carbapenems against Pseudomonas aeruginosa was comparable to that of CAZ, and there were some resistant strains.

Carbapenems↗

Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia.

The purpose of this study was to investigate the biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia (ALL). We carried out in vitro tests with a 4-day culture and a methyl-thiazol-tetrazolium assay on bone marrow samples from 209 children newly diagnosed with ALL. After testing the resistance of leukemic cells to 14 drugs, we classified the patients into two groups according to their sensitivity to three drugs (prednisolone, L-asparaginase, and vincristine) used in remission induction therapy. The three-drug resistant group (RR: sensitive to no drugs or to one drug) correlated with both short-term and long-term treatment failure. Three-year event-free survival (95% confidence interval) for the sensitive group (SS: sensitive to two or three drugs) was 0.813 (0.773-0.853) and that of the RR group was 0.616 (0.569-0.669) (P = 0.0001). Univariate analysis showed that Philadelphia-chromosome (Ph1) positivity and immunophenotype of mixed lineage were also prognostic factors in the 209 patients. The prognosis of the SS/RR drug resistance profile within 14 Ph1 patients was marginally significant (P = 0.062). Multivariate Cox regression analysis showed that Ph1 was an overwhelmingly adverse factor in event-free survival, with a relative hazard of 5.37 (2.57-11.21, P < 0.0001), followed by RR, with a relative hazard of 2.98 (1.69-5.25, P = 0.0001). Furthermore, we clarified the characteristics of the RR group by examination of the pattern of drug resistance to other drugs in comparison with the SS group. The leukemic cells of RR patients were more resistant than those of SS patients (P < 0.0001) to all the drugs tested, with resistance ratios of 1.6 to 13.1 (mean 3.4). In conclusion, in vitro three-drug resistance at the initial stage is an important independent predictor of treatment failure for both induction response and long-term outcome in childhood ALL.

Adolescent↗

Human colon cancer cells express the functional Fas ligand.

Fas ligand (FasL) belongs to the TNF superfamily. It is induced in activated lymphocytes and eliminates Fas-positive lymphocytes, resulting in the down-regulation of immune responses. FasL has also been detected in tissues other than lymphoid cells. We investigated the expression and function of FasL on human colon cancer cells. FasL mRNA was detected by RT-PCR in all six colon cancer cell lines tested and was not found on fibroblasts. FasL protein was detected in DLD-1, LoVo, HCT-116 and RPMI 4788 cells by immunohistochemical staining. DLD-1, LoVo and WiDr were cytotoxic against mouse T lymphoma cells which were transfected with human Fas receptor cDNA. The cytotoxicity was significantly enhanced by phorbol 12-myristate 13-acetate (PMA) and ionomycin. Our data suggest that the FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitates the escape from the host immune system.

Apoptosis↗

In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia.

It is vital to develop effective therapy for children with acute lymphoblastic leukemia (ALL), in whom no remission occurs or who suffer relapse with current protocols. Cellular drug resistance is thought to be an important cause of induction failure and relapse. We performed in vitro tests of bone marrow samples in 196 children with newly diagnosed ALL with a 4-day culture and a methyl-thiazol-tetrazolium assay. We tested 16 drugs and calculated the 70% lethal dose (LD70) for 14 drugs and the leukemic cell survival (LCS) rate for dexamethasone and prednisolone. For each single drug, patients were classified into two groups, sensitive or resistant, by median concentration of LD70 or LCS. When patients were classified into three groups by sensitivity to four drugs of DPAV (dexamethasone, prednisolone, L-asparaginase, and vincristine), 3-year event-free survival (EFS; 95% confidence intervals) of the super sensitive group (SS; sensitive to all 4 drugs) was 0.833 (0.690 to 0.976), that of the intermediate sensitive group (IS; sensitive to 2 or 3 drugs) was 0.735 (0.609 to 0.863), and that of the relatively resistant group (RR; sensitive to no drugs or to 1 drug) was 0.541 (0.411 to 0.670; P = .0008). We then investigated the relationship between the above four-drug sensitivity and the time of relapse. The SS and IS patients tended to maintain continuous complete remission, and RR patients tended to undergo induction failure and early and late relapse (P = .004). Initial white blood cell count, immunologic classification, and age were also predictive factors, but the patient numbers showed no statistical correlation between these factors and the four-drug sensitivity groups (SS, IS, and RR). When we took three groups SS/IS/RR and investigated the EFS for various clinical groups, DPAV sensitivity strongly influenced EFS in the standard-risk ALL (P = .016). In vitro drug sensitivity testing provides additional prognostic information about childhood ALL, and early detection of drug resistance at the time chemotherapy commences may provide a successful strategy for individualizing treatment, as the results indicate de novo resistance to front-line drugs and suggest alternative, second-line drugs.

Aclarubicin↗

Synthesis and cataleptic effects of optically active dihydrohaloperidols and dihydrobromoperidols.

Optically active dihydrohaloperidols and dihydrobromoperidols, the major metabolites of haloperidol and bromoperidol, clinically used as neuroleptic drugs in humans, were asymmetrically synthesized by Jaen's method. The motor effects of all the reduced haloperidol and bromoperidol metabolites were evaluated by the mouse catalepsy test. The results indicate that administration of the optically active dihydrohaloperidols and dihydrobromoperidols as well as haloperidol and bromoperidol can cause significant motor deficits in mice.

Animals↗

[Alterations of the p53 gene and clinical features in childhood acute lymphoblastic leukemia].

Correlations between alterations of the p53 gene and clinical features were examined in childhood acute lymphoblastic leukemia (ALL). We analyzed 147 patients and 38 cell lines for p53 mutations within exons 5 to 9 (2 to 11 in some of them) by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. p53 gene mutations were found in 3 of 62 (5%) patients at diagnosis, 1 of 14 (7%) patients at relapse, and 13 of 20 (65%) cell lines in T-ALL, 2 of 20 (10%) patients at diagnosis, 4 of 4 (100%) patients at relapse, and 4 of 5 (80%) cell lines in t(1;19)-ALL, 1 of 23 (4%) patients at diagnosis, 2 of 22 (9%) patients at relapse, and 5 of 12 (42%) cell lines in common ALL other than t(1;19) or t(9;22)-ALL and 3 of 3 (100%) patients at diagnosis in B-ALL. In t(1;19)-ALL, p53 gene alterations were associated with a poor prognosis. The patients with p53 mutations had a trend towards poor prognosis in childhood ALL without B-ALL. p53 gene mutation is not always associated with the current prognostic factors. This alteration may become one of the important prognostic factors, if the detection of a small number of the leukemic cells with the p53 gene mutation would be possible.

Adolescent↗

Infrequent mutations of the TP53 gene and no amplification of the MDM2 gene in hepatoblastomas.

We have investigated the mutation of the TP53 gene in hepatoblastomas (HBLs) by using polymerase chain reaction-single strand conformation polymorphism and direct sequencing in 38 HBL tumor samples and in two HBL cell lines. We detected the TP53 gene mutation in an anaplastic hepatoblastoma cell line, but no aberration of the TP53 gene (exons 5-9) was found in tumor samples and in the other HBL cell line. The mutation of the cell line was a missense mutation from GAC (asparagine) to CAC (histidine) at codon 281, which was different from the G-to-T transversion of codon 249 that is frequently found in adult hepatocellular carcinomas (HCCs). In addition, we performed Southern blot analysis of the MDM2 gene, but we did not find MDM2 gene amplification in 19 cases tested. Our results suggest that, in contrast to the findings in HCCs in adults, TP53 gene aberrations are not involved in the development or progression of HBLs in children.

Adult↗

Convergence of skin reflex and corticospinal effects in segmental and propriospinal pathways to forelimb motoneurones in the cat.

The organization of facilitatory convergence from cutaneous afferents (Skin) and the corticospinal tract (pyramidal tract, Pyr) in pathways to forelimb motoneurones of mainly distal muscles was studied in anaesthetized cats by analysing postsynaptic potentials (PSPs), which were spatially facilitated by combinations of stimuli to the two sources at different time intervals. Conditioning Pyr volleys facilitated Skin-evoked PSPs of fixed (1.2-3.6 ms) central latencies (Skin PSPs), suggesting that disynaptic and polysynaptic skin reflex pathways are facilitated from the pyramidal tract. The shortest latencies (1.2-1.7 ms) of pyramidal facilitation suggested direct connection of pyramidal fibres with last order neurones of skin reflex pathways. Conditioning Skin volleys facilitated Pyr-evoked PSPs of fixed, mostly disynaptic latencies (1.0-2.5 ms; Pyr PSPs), suggesting that pyramido-motoneuronal pathways are facilitated from Skin at a premotoneuronal level. The shortest pathway from skin afferents to the premotor neurones appeared to be monosynaptic. Although Pyr and Skin volleys were mutually facilitating, the facilitation curve of Pyr PSPs and that of Skin PSPs were discontinuous to each other, with the peak facilitation at different Skin-Pyr volley intervals. Transection of the dorsal column (DC) at the C5/C6 border had little effect on the latencies or amplitudes evoked by maximal stimulation and the pyramidal facilitation of Skin PSPs. In contrast, the facilitation of Pyr PSPs by Skin stimulation was greatly decreased after the DC transection, and the facilitation curve of Pyr PSPs was continuous to that of Skin PSPs, with no separate peak. Latencies of Pyr PSPs ranged similarly to those in DC intact preparations. More rostral DC transection (C4/C5 border) reduced Skin-facilitated Pyr excitatory PSPs (EPSPs) less than C5/C6 lesions, suggesting that the C5 segment also contains neurones mediating Skin-facilitated Pyr EPSPs. The results show that convergence from skin afferents and the corticospinal tract occurs at premotor pathways of different cervical segments. We suggest that corticospinal facilitation of skin reflex occurs mostly in the brachial segments and Skin facilitation of cortico-motoneuronal effects takes place largely in the rostral cervical segments and partly in the brachial segments.

Animals↗

Iron nutrition and anaemia in a malaria-endemic environment: haematological investigation of the Gidra-speaking population in lowland Papua New Guinea.

Blood examination was conducted for the four Gidra-speaking village groups in Papua New Guinea, who were characterized by high Fe intake and high malaria prevalence with marked inter-village differences. The northern riverine villagers, whose Fe intake was higher than the other three village groups, did not suffer from Fe-deficiency anaemia in their malaria-endemic environment; nor did the inland villagers, with their second highest Fe intake and their malaria-free environment, suffer from Fe-deficiency anaemia. However, several individuals of the southern riverine village suffered from anaemia in a malaria-endemic environment, although their Fe intake was almost the same as the inland villagers'. A considerable proportion of the coastal villagers were anaemic, reflecting the lowest Fe intake and the highest malaria prevalence. An inter-village comparison of the relationships between haemoglobin levels and transferrin saturation revealed that the southern riverine villagers needed smaller amounts of circulating Fe for erythropoiesis than the northern riverine and inland villagers, reflecting the long-term human-environment conditions such as the density of malaria vectors and the people's dietary habits. Fe supplementation was not judged effective against hypoferraemia and/or anaemia in such a population. As the incidence of malaria had no significant long-lasting effect on Fe stores or circulating Fe concentration, but did have an effect on anaemia, the hypothesis that malaria causes a transfer of Fe from the blood to parenchymal tissues as a defence against infectious diseases was not supported.

Anemia, Iron-Deficiency↗