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Indalo, DM.  Submitted.  Factors Affecting Patients Retention And Defaulter Rates In An Anti-retroviral Therapy Program. Abstract

The purpose of this research was to determine patients' retention and associated factors in the Antiretroviral Therapy (ART) program. Specifically, it establishes factors that contribute to patients' retention and recommends the appropriate strategies that enhance sustainable retention of patients in the ART program. The case studies were carried out at Kibera Community Based Health Care project/clinic - AMREF intervention area in Kibera slum
A descriptive cross-sectional method was employed aimed at collecting information from the patients in the program through random sampling, while stratified sampling was used to pick on defaulters, who were traced by Community Health Workers as well as key informants. A representative sample constituted 357 patients in the ART program, 27 defaulters and 8 Health Care Providers of the total population of patients in the program. Quantitative data was collected using a standardized questionnaire administered to the study participants in the program and defaulters. Qualitative data
was obtained through; focus Group Discussion and Key informants interviews. Ethical consideration and risk to human subjects was put into consideration, through provision of willing consent and confidentiality upheld at all times.
The study reveals that AMREF in Kenya, Kibera project continues to playa leading role in the fight against HIV/AIDS. A majority of the respondents (69%) confirmed to have disclosed their HIV status to someone while 31% were categorical that they have not disclosed their status to anyone. It is imperative to point out that disclosure levels were high (88%) amongst respondents in the 51-55 years age group and closely followed by those in the 41-45 years age group (77%). The study also found out that 49.5% of the respondents were on the affirmative that indeed they find it easy discussing their challenges with their clinicians, while 50.5% noted that they do not find it easy. It is
interesting to observe that the challenges of side effects related to ARV are more pronounced amongst those who skip appointments at the clinic compared to stigma and lack of food. A considerable number (15%) of the respondents noted that they like the clinic as it provides free ARVs while 4% lauded the good counseling services offered at the clinic. Some 3% liked the facility as it was near to their areas of residence. Asked to state the reasons why they would prefer other ART clinics, most of the respondents (63%) pointed to the distance from their areas of residence, 14% made reference to the quality of services while 8% explained that they would prefer other clinics if they offer food supplements as part of the program.
In conclusion psycho-social counseling appeared the most preferred service in the facility, it enforces adherence to medication and also reduces stigma related condition among the patients and those around them. MSF Belgium clinics were most preferred clinic in Kibera slum; AMREF Kibera project management should consider exchange visits to their sites and learn from each other. The study detects that there is a cross cutting call from the study approach that an ideal ART programme should provide comprehensive care and support (37%) and offer free medical care (15%) to enhance
accessibility besides integrating PTC (7%) among others as captured from the interviews with defaulters. Service delivery it was suggested should also be done professionally without unethical and coercive practices such sexual harassment among other malpractices that accentuate default.
AMREF Kibera project should consider to networking and collaborating with other organizations that are working in informal settlement to learn and share best practice to enhance adherence to ART care. Address the attitude of health care providers in the facility through trainings, supervision and assessment of care. The project should also review its approach to ART care and through operation research to boost ART care in marginalized communities in the informal settlements.

2005

Maxwell, TJ, Ameyaw M-M, Pritchard S, Thornton N, Folayan G, Githang'a J, Indalo A, Tariq M, Mobarek A, Evans DA, Ofori-Adjei D, Templeton AR, McLeod HL.  2005.  Beta-2 adrenergic receptor genotypes and haplotypes in different ethnic groups., 2005 Oct. International journal of molecular medicine. 16(4):573-80. Abstract

The human beta-2 adrenergic receptor (beta2AR) is responsible for the binding of endogenous catecholamines and their exogenously administered agonists and antagonists. Three functional polymorphisms in codons 16, 27 and 164 have been described which have clinical importance for several diseases, including asthma, hypertension, heart failure, cystic fibrosis and obesity, as well as response to beta-agonist therapy. These were evaluated in 726 individuals from 8 distinct ethnic populations (Chinese, Filipino, Southwest Asian, Saudi, Ghanaian, Kenyan, Sudanese, and European from Scotland). The results show that most haplotypes are shared among all populations, yet there are marked differences in their frequency distributions geographically. The genetic distance tree is different from standard human population distance trees, implying a different mode of evolution for this locus than that for human population gene-flow history. The multilocus frequency differences between the observed clusters of populations correspond to historical haplotype groupings that have been found to be functionally different with respect to multiple medically related phenotypes. Further studies are needed to see if functional relationships are the same across populations.

2001

Ameyaw, MM, Regateiro F, Li T, Liu X, Tariq M, Mobarek A, Thornton N, Folayan GO, Githang'a J, Indalo A, Ofori-Adjei D, Price-Evans DA, McLeod HL.  2001.  MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity., 2001 Apr. Pharmacogenetics. 11(3):217-21. Abstract

P-glycoprotein (PGP), the product of the multidrug resistance gene (MDR1), acts as an energy-dependent efflux pump that exports its substrates out of the cell. PGP expression is an important factor regulating absorption of a wide variety of medications. It has also been associated with intrinsic and acquired cross resistance to a number of structurally unrelated anticancer drugs. A single nucleotide polymorphism (SNP) in exon 26 of the MDR1 gene, C3435T, was recently correlated with PGP protein levels and substrate uptake. Individuals homozygous for the T allele have more than four-fold lower PGP expression compared with CC individuals. As overexpression of PGP has been associated with altered drug absorption, therapy-resistant malignancies, and lower concentrations of HIV-1 protease inhibitors, this SNP may provide a useful approach to individualize therapy. To facilitate clinical application throughout the world, 1280 subjects from 10 different ethnic groups were evaluated for this SNP using the polymerase chain reaction-restriction fragment length polymorphism assay and the genotype and allele frequency for each group were ascertained. Marked differences in genotype and allele frequency were apparent between the African populations and the Caucasian/Asian populations (P < 0.0001). The Ghanaian, Kenyan, African American and Sudanese populations studied had frequencies of 83%, 83%, 84% and 73%, respectively, for the C allele. The British Caucasian, Portuguese, South-west Asian, Chinese, Filipino and Saudi populations had lower frequencies of the C allele compared to the African group (48%, 43%, 34%, 53%, 59%, and 55%, respectively). The high frequency of the C allele in the African group implies overexpression of PGP and may have important therapeutic and prognostic implications for use of PGP dependent drugs in individuals of African origin.

2000

Marsh, S, Ameyaw MM, Githang'a J, Indalo A, Ofori-Adjei D, McLeod HL.  2000.  Novel thymidylate synthase enhancer region alleles in African populations., 2000 Dec. Human mutation. 16(6):528. Abstract

Thymidylate synthase (TS) regulates the production of DNA synthesis precursors and is an important target of cancer chemotherapy. A polymorphic tandem repeat sequence in the enhancer region of the TS promoter was previously described, where the triple repeat gives higher in vitro gene expression than a double repeat. We recently identified ethnic differences in allele frequencies between Caucasian and Asian populations. We now describe assessment of genotype and allele frequencies of the TS polymorphism in 640 African (African American, Ghanaian and Kenyan) and Caucasian (UK, USA) subjects. The double and triple repeat were the predominant alleles in all populations studied. The frequency of the triple repeat allele was similar between Kenyan (49%), Ghanaian (56%), African American (52%), American Caucasian (54%) and British Caucasian (54%) subjects. However, two novel alleles contained 4 and 9 copies of the tandem repeat. These novel alleles were found at a higher allele frequency in African populations (Kenyan 7%, Ghanaian 3%, African American 2%) than Caucasians (UK 1%, USA 0%). The novel alleles identified in this study decrease in frequency with Western migration, while the common alleles are relatively stable. This is a unique example suggesting the influence of multiple selection pressures within individual populations. Hum Mutat 16:528, 2000.

1999

McLeod, HL, Pritchard SC, Githang'a J, Indalo A, Ameyaw MM, Powrie RH, Booth L, Collie-Duguid ES.  1999.  Ethnic differences in thiopurine methyltransferase pharmacogenetics: evidence for allele specificity in Caucasian and Kenyan individuals., 1999 Dec. Pharmacogenetics. 9(6):773-6. Abstract

Thiopurine methyltransferase (TPMT) degrades 6-mercaptopurine, azathioprine and 6-thioguanine which are commonly used in the treatment of autoimmune diseases, leukaemia and organ transplantation. TPMT activity is polymorphic as a result of gene mutations. Heterozygous individuals have an increased risk of haematological toxicity after thiopurine medication, while homozygous mutant individuals suffer life threatening complications. Previous population studies have identified ethnic variations in both phenotype and genotype, but limited information is available within African populations. This study determined the frequency of common TPMT variant alleles in 101 Kenyan individuals and 199 Caucasians. The frequency of mutant alleles was similar between the Caucasian (10.1%) and Kenyan (10.9%) populations. However, all mutant alleles in the Kenyan population were TPMT*3C compared with 4.8% in Caucasians. In contrast TPMT*3A was the most common mutant allele in the Caucasian individuals. This study confirms ethnic differences in the predominant mutant TPMT allele and the findings will be useful for the development of polymerase chain reaction-based strategies to prevent toxicity with thiopurine medications.

1997

Munenge, RW, Achola KJ, Indalo AA.  1997.  Pharmacological activities of pistia stratiotes. Abstract

The pharmacologic activities of Pistia stratiotes were studied. Calcium channel blocking activity of a methanol extract of the whole plant was demonstrated using isolated segments of rabbit jejunum and confirmed via inhibition by pretreatment with verapamil. Additionally, the plant extract exhibited dose-related bronchodilating activity on isolated guinea pig trachea and neuromuscular blocking action, which was also dose-related. The plant extract caused a decrease in blood pressure in anaesthetised rats. After a 10 μg dose of the extract, systolic and diastolic blood pressures fell by 18% and 10%, respectively. Further doses of the plant extract produced slight decreases in blood pressures in anaesthetised rats. The systolic, diastolic and mean blood pressures before the extract were all significantly higher (P < 0.001) than those following the administration of the extract

A, DRINDALOANNE.  1997.  Antibiotic sale behaviour in Nairobi: a contributing factor to antimicrobial drug resistance.East Afr Med J. 1997 Mar;74(3):171-3.. East Afr Med J. 1997 Mar;74(3):171-3.. : The Indian Journal of Animal Sciences Abstract

A survey of antibiotic sale behaviour in retail chemist shops in Nairobi revealed that about 64% of chemists sell antibiotics without prescriptions from doctors. Most shops sold underdose drugs according to the request of the patient. The practice is more common in peri-urban than city centre chemists. Out of the 128 chemist shops visited, 82 sold the antibiotic, 33 sent the patients to go and see the doctors while 13 did both. Sixty eight per cent of the chemists in the city centre recommended the taking of full antibiotic course to the patients while only 46% in peri-urban centres did so. Even after the recommendation, some of the chemists still sold under dose drugs. Some of the drugs were sold in envelopes without any instruction at all and none of the drugs sold were fully labelled. Only seven chemists sold septrin, the brand of co-trimoxazole requested by the patients, the rest sold various brands of the drug some of whom still labelled the brands 'septrin'.

1996

A, DRINDALOANNE.  1996.  Kokwaro GO, Indalo AA.Metabolism of Diazepam and Ethosuximide in rats with malaria and endotoxin-induced fever. Afr J Health Sci. 1996 Feb;3(1):22-6.. 1: Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):13-6. : The Indian Journal of Animal Sciences Abstract
We have investigated the effects of malaria infection with rodent parasite Plasmodium berghei and fever induced by Escherischia coli endotoxin on the metabolism of diazepam to temazepam by rat liver microsomes, and on the clearance of ethosuximide in vivo in the rat. Livers from malaria-infected (parasitaemia =36.8+/- 7.6% endotoxin-treated or saline-treated (control) rats (N=5 per treatment) were used to prepare microsomes. These were incubated with diazepam (10-600ū M) for 10 minutes in an NADPH-generating system. V( max), K(m ) and the intrinsic clearance V(max )/K(m ) for the production of temazepam were determined. In separate experiments, ethosuximide (5mg/kg) was administered via the tail vein to control, malaria-infected and endotoxin-treated rats (parasitaemia=43.8+/- 5 %) under light ether anesthesia (N=5 per treatment). Total clearance of ethosuximmide was estimated form a single blood sample obtained 24h after drug administration. Diazepam metabolism was not affected by malaria infection or fever (V(max ):1.31+/- 0.34,0.73+/- 0.27 and 1.07+/- 0.78 nmol/min/mg protein; K( m): 158.7 +/- 63.7, 175.3+/- 44.9 and 190.0+/- 81.8ūM; Intrinsic clearance/whole liver: 0.31+/- 0.16, 0.26+/- 0.1 and 0.29+/- 0.1ml/min in livers from control, malaria-infected and endotoxin-treated rats respectively; P>0.05). Similarly, clearance of ethosuximide in vivo was not affected by malaria infection or fever (1.3+/- 0.2, 1.3+/- 0.01 and 1.4+/- 0.4 ml/min/kg in control, malaria-infected and endotoxin-treated rats respectively; p>0.05). These results suggest that malaria infection and fever have no effect on the activities of the CYP3A isozymes thought to be involved in the metabolism of diazepam and ethosuximide.
A, DRINDALOANNE.  1996.  Kokwaro GO, Indalo AA.Effect of route of administration on systematic availability of oxamniquine in the rabbit. Afr J Health Sci. 1996 Aug;3(3):101-4.. 1: Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):13-6. : The Indian Journal of Animal Sciences Abstract
Eight New Zealand white rabbits (4 females, 4 males) each received oxamniquine (15 mg kg(-1)) orally, rectally, intravenously and via the hepatic portal vein in a random cross-over study. Serial plasma samples were obtained for up to 10 hours post drug administration and the bioavailable fraction was calculated, with reference to the intravenous route, from areas under plasma drug concentration-time profiles. Estimated fractions available were approximately 1.0, 0.45 and 0.46 respectively, for portal vein, oral and rectal routes. Hepatic "first-pass" metabolism appeared to be negligible. Low oral availability suggested incomplete absorption and/or metabolism within gastrointestinal wall. Rectal administration resulted in comparable availability to oral administration. These results suggest that if a suitable formulation can be developed, then rectal administration of oxamniquine may provide an alternative to oral administration in patients who cannot take drug orally.
A, DRINDALOANNE.  1996.  Pharmacokinetics of oxamniquine in rabbit and rat.Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):13-6. 1: Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):13-6. : The Indian Journal of Animal Sciences Abstract
The pharmacokinetics of the schistosomicidal agent oxamniquine (6-hydroxmethyl-2-isopropylaminomethyl-7-nitro-1,2,3,4-tetra hydroquinoline) were studied in 8 (4 male, 4 female) New Zealand White rabbits and 5 female Wistar rats, following intravenous administration (15 mg/kg). The pharmacokinetic parameters (mean +/- SD) in the rabbit and rat, respectively, were as follows: plasma clearance, 65.5 +/- 33 and 17.2 +/- 5.7 ml/min/kg; steady-state volume of distribution, 7.9 +/- 4.5 and 2.1 +/- 0.5 l/kg; terminal elimination half-life, 1.8 +/- 0.3 and 1.8 +/- 0.9 h. Oxamniquine appeared to be widely distributed in both species, although significantly higher in the rabbit. Similarly, plasma clearance was significantly higher in the rabbit. Using reported estimates of liver blood flow and fractions excreted unchanged in urine of the rabbit and rat, calculations based on blood clearances indicated that oxamniquine has a low hepatic extraction ratio (0.2) in the rat and an intermediate hepatic extraction ratio (0.6) in the rabbit. From separate experiments, however, hepatic extraction appeared to be low in the rabbit, suggesting that oxamniquine disposition is probably broadly similar in both rabbit and rat.
A, DRINDALOANNE.  1996.  Kokwaro GO, Indalo AA.Oxamniquine inhibits metabolism of caffeine, hexobarbitone and antipyrine in vivo in mice. Afr J Health Sci. 1996 Aug;3(3):105-8.. 1: Eur J Drug Metab Pharmacokinet. 1996 Jan-Mar;21(1):13-6. : The Indian Journal of Animal Sciences Abstract
Inhibition of hepatic metabolism of caffeine (as assessed from expiration of (14)CO(2) resulting from N-demethylation of (14)C-labelled caffeine), hexobarbitone (as assessed from sleeping times) and antipyrine (as assessed from expiration of I4CO2 resulting from the oxidation of "C-labelled antipyrine) was studied in male GB-1 mice administered a single SO mg kg-1 oral dose of the schistosomicidal drug oxamniquine. Metabolism of caffeine, catalysed by cytochrome P-4S0 1A2(CYP1A2), was inhibited most, while hexobarbitone and antipyrine metabolism were inhibited to a lesser, though significant, degree. These results indicate a need for further studies to investigate possible clinically relevant inhibition of hepatic drug metabolism by oxamniquine.
A, DRINDALOANNE.  1996.  Steady-state anticonvulsant drug levels in epileptic patients.East Afr Med J. 1996 Oct;73(10):679-82.. East Afr Med J. 1996 Oct;73(10):679-82.. : The Indian Journal of Animal Sciences Abstract
Steady state concentrations of three anticonvulsant drugs (phenobarbitone, phenytoin and carbamazepine) were measured in plasma samples from fifteen patients (eight males and seven females; ages: 13-49 years; body weights: 44-70 kg), attending the outpatient Neurology Clinic at Kenyatta National Hospital. In addition, total protein and albumin levels were measured in plasma from patients taking phenytoin. Total protein levels were normal (range: 6.3-7.6 g/dl) in all patients except in one patient (10.7 g/dl). Albumin levels were also normal (range: 3.7-4.1 g/dl) in all patients except one (25.4 g/dl). One patient on phenobarbitone and three patients on phenytoin had no detectable drug levels in their plasma. In the remainder, phenobarbitone, phenytoin and carbamazepine steady state concentrations were 8.7-21.1 mg/L (N = 8), 9.3-27.3 mg/L (N = 6) and 10-19.7 mg/L (N = 5), respectively. The unbound fraction of phenytoin in plasma (fu) was normal(approximately 0.1) in six patients, but relatively high (0.2) in one patient. Most patients in the study complied with the prescribed treatment and their epilepsy was controlled. Cases where drug levels were undetectable probably arose from a lack of money to purchase all prescribed medicines rather than deliberate non-compliance. Routine monitoring of anticonvulsant drug levels may improve management of epileptic patients

1995

A, DRINDALOANNE.  1995.  Pharmacokinetics of temazepam in male surgical patients.East Afr Med J. 1995 Aug;72(8):483-5. East Afr Med J. 1995 Aug;72(8):483-5. : The Indian Journal of Animal Sciences Abstract
The pharmacokinetics of temazepam, the 3-hydroxy1 derivative of diazepam, were studied in nine male surgical patients (age: 28-57 years; weight: 55-87 kg) who had ingested single 40 mg doses, 4 hours prior to minor surgical procedures. Peak plasma temazepam concentrations were achieved rapidly (within 1 h post drug administration) and the estimated volume of distribution (mean: 1.13 1/kg), total clearance (mean: 1.6 ml/min/kg) and terminal elimination half-life (mean: 8 hours) were comparable to previously reported values in healthy subjects. There was no correlation between volume of distribution and either weight or age, and between clearance and age. These findings are broadly consistent with previous reports from studies in healthy subjects. Temazepam can therefore be used as a premedicant in patients requiring minor surgery; the concomitant anaesthetic agents administered and the surgical procedures have no effects on temazepam pharmacokinetics

1989

A, DRINDALOANNE.  1989.  Premedication with temazepam in minor surgery. The relationship between plasma concentration and clinical effect after a dose of 40 mg.Anaesthesia. 1989 Oct;44(10):812-5. Anaesthesia. 1989 Oct;44(10):812-5. : The Indian Journal of Animal Sciences Abstract
Fourteen patients received oral premedication of temazepam in soft gelatin capsules before minor surgery. The plasma concentrations of temazepam and its sedative, anxiolytic and amnesic effects were measured for 24 hours. Absorption was rapid and peak concentrations occurred 49 minutes after administration. Clinical effects were evident at 30 minutes and persisted for about 4 hours. The decline in plasma concentration was biexponential with a distribution half-life of 1.24 hours. The end of the distribution phase coincided approximately with the termination of its clinical effects. A relationship between plasma concentration and effect was observed; concentrations above 300 ng/ml produced measurable changes in tests of mental function. Patients had recovered fully from the effects of temazepam after 24 hours. This dose of temazepam is reliable and effective as premedication before surgery

1986

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