Erectile Dysfunction: Prevalence, and Pattern among Adult Male Patients Attending the General Out-Patient Clinic of Federal Medical Centre Bida, Nigeria.

BACKGROUND: Erectile dysfunction (ED) is usually underestimated in many developing countries, Nigeria inclusive. INTRODUCTION: ED is associated with stigma and poor health seeking behaviour and is assumed not to be life-threatening. This study was undertaken to determine the prevalence of ED and the pattern among adult males. METHODS: The study was a cross-sectional hospital-based survey among 360 sexually active men aged 18 years and above seen in the GOPC of Federal Medical Centre, Bida. Self-reported ED was obtained using a structured questionnaire administered by an interviewer. The prevalence and severity of ED was obtained using the International Index of Erectile Function-5 Questionnaire (IIEF-5). RESULTS: The age range of respondents was 22-75 years with a mean age of 42.06(11.35) years. The prevalence of ED was 56.4%, with 29.4% having mild ED, 24.2% had mild-moderate ED and 2.8% had moderate ED. The prevalence of ED was noted to increase with increasing age as ED was more prevalent (100%) among men aged 70-79 years and least common among the younger (20-29) subjects (30.9%). Most of the respondents 198 (54.9%) had sexual intercourse at least thrice a week, while only 158 (43.9%) of respondents were extremely satisfied with their sexual life. About 175 (48.6%) of the respondents had experienced embarrassment over sexual performance, while a greater proportion of the respondents 239 (66.4%) had used performance-enhancing drugs. Despite this, only 20 (5.6%) of the respondents had ever complained of ED in the hospital. Traditional and over-the-counter (OTC) drugs were the commonest source of performance-enhancing drugs 106 (44.4%). CONCLUSION: Erectile dysfunction is a common medical and social problem in our environment. Physicians should routinely ask their patients about their sexual health and erectile dysfunction.

CONTEXTE: La dysfonction érectile (DE) est généralement sousestimée dans de nombreux pays en développement, le Nigeria inclus. INTRODUCTION: La DE est associée à la stigmatisation et à un comportement médiocre en matière de recherche de soins de santé et est supposée ne pas mettre la vie en danger. Cette étude a été entreprise pour déterminer la prévalence de la DE et son profil chez les hommes adultes. MÉTHODES: L'étude était une enquête transversale en milieu hospitalier auprès de 360 hommes sexuellement actifs âgés de 18 ans et plus, vus dans la GOPC du Centre médical fédéral de Bida. La DE auto-déclarée a été obtenue à l'aide d'un questionnaire structuré administré par un enquêteur. La prévalence et la gravité de la DE ont été obtenues à l'aide du questionnaire International Index of Erectile Function-5 (IIEF-5). RÉSULTATS: La tranche d'âge des répondants était de 22 à 75 ans, avec un âge moyen de 42,06 (11,350) ans. La prévalence de la DE était de 56,4 %, avec 29,4 % présentant une DE légère, 24,2 % une DE légère à modérée et 2,8 % une DE modérée. La prévalence de la DE a été notée pour augmenter avec l'âge croissant, car la DE était plus fréquente (100 %) chez les hommes âgés de 70 à 79 ans et moins courante chez les sujets plus jeunes (20-29 ans) (30,9 %). La plupart des répondants, 198 (54,9 %), avaient des rapports sexuels au moins trois fois par semaine, tandis que seuls 158 (43,9 %) étaient extrêmement satisfaits de leur vie sexuelle. Environ 175 (48,6 %) avaient ressenti de l'embarras quant à leur performance sexuelle, et une proportion plus importante des répondants, 239 (66,4 %), avaient utilisé des médicaments améliorant les performances. Malgré cela, seulement 20 (5,6 %) s'étaient déjà plaints de la DE à l'hôpital. Les médicaments traditionnels et en vente libre étaient la source la plus courante de médicaments améliorant les performances, avec 106 (44,4 %). CONCLUSION: La dysfonction érectile est un problème médical et social courant dans notre environnement. Les médecins devraient régulièrement interroger leurs patients sur leur santé sexuelle et la dysfonction érectile. MOTS-CLÉS: Dysfonction érectile, Homme, Profil, Prévalence.

Anthropometric Indices for Predicting Hypertension among General Outpatient Clinic Attendees of Federal Medical Centre, Bida, Nigeria.

BACKGROUND: The literature is replete with overwhelming evidence that being obese is a predictor of hypertension risk. Obesity can be defined by anthropometric indices, such as Body Mass Index (BMI), Waist Circumference (WC), waist-hip ratio (WHR), and waistheight ratio (WHtR). Despite wide use of BMI as indicator of obesity, it does not reflect central fat distribution, whereas WC, WHR, and WHtR are used as surrogate markers for body fat centralization. A central distribution of body fat has been shown to be strongly associated with hypertension. Controversies, however, remain regarding the best predictor of hypertension risk. We determined the prevalence of hypertension and assess its association with the four obesity-related indices above. We evaluated which anthropometric measurement most closely relates to high blood pressure risk among adult patients 18 years and above in Bida. METHODS: This is an analytical cross-sectional hospital-based study of 210 systematic randomly selected adults. Participants were administered a standardized questionnaire and had anthropometric measurements taken along with their blood pressure. RESULTS: The percentage of people with high blood pressure was 38.6% (33.7% for males and 42.4% for females). WC (p-value <0.001), WHR (p-0.001), WHtR (p-value <0.001) and BMI (p-0.016) were all statistically significantly associated with hypertension. At the multivariate analysis level; waist circumference (OR= 3.635, p= 0.002, CI = 1.613-8.189) and waist-height ratio (OR= 7.183, p-value <0.001, CI = 2.661-19.389) remained strong predictors of hypertension risk. Analysis of the receiver operated characteristics curve showed that waist circumference (0.842) and waist-height ratio (0.838) were the best predictors of hypertension risk. CONCLUSION: The central obesity indices WC, and WHtR were better than BMI for the prediction of hypertension in adults >18 years. Therefore, WHtR or WC is recommended as a screening tool for the prediction of hypertension in our clinics, as a means of prevention and early detection of hypertension to halt or slow down the rising burden of hypertension.

CONTEXTE: La littérature regorge de preuves irréfutables que l'obésité est un facteur de prédiction du risque d'hypertension. L'obésité peut être définie par des indices anthropométriques, comme l'indice de masse corporelle (IMC), le tour de taille (TT), le rapport taille-hanche (RTH) et le rapport taille-hauteur (RTH). Bien que l'IMC soit largement utilisé comme indicateur de l'obésité, il ne reflète pas la distribution centrale de la graisse, alors que le tour de taille, le WHR et le WHtR sont utilisés comme marqueurs de substitution pour la centralisation de la graisse corporelle. Il a été démontré qu'une distribution centrale de la graisse corporelle est fortement associée à l'hypertension. Cependant, des controverses subsistent quant au meilleur prédicteur du risque d'hypertension. Nous avons déterminé la prévalence de l'hypertension et évalué son association avec les quatre indices liés à l'obésité ci-dessus. Nous avons évalué quelle mesure anthropométrique est la plus étroitement liée au risque d'hypertension chez les patients adultes âgés de 18 ans et plus à Bida. MÉTHODES: Il s'agit d'une étude analytique transversale menée en milieu hospitalier auprès de 210 adultes sélectionnés de manière systématique et aléatoire. Les participants ont reçu un questionnaire standardisé et des mesures anthropométriques ont été prises en même temps que leur tension artérielle. RÉSULTATS: Le pourcentage de personnes ayant une pression artérielle élevée était de 38,6 % (33,7 % pour les hommes et 42,4 % pour les femmes). Le tour de taille (valeur p <0,001), le WHR (p-0,001), le WHtR (valeur p <0,001) et l'IMC (p-0,016) étaient tous associés de manière statistiquement significative à l'hypertension. Au niveau de l'analyse multivariée, le tour de taille (OR= 3,635, p=0,002, CI = 1,613-8,189) et le rapport taille-hauteur (OR= 7,183, pvalue <0,001, CI = 2,661-19,389) sont restés des prédicteurs forts du risque d'hypertension. L'analyse de la courbe des caractéristiques opérées par le récepteur a montré que le tour de taille (0,842) et le rapport taillehauteur (0,838) étaient les meilleurs prédicteurs du risque d'hypertension. CONCLUSION: Les indices d'obésité centrale WC, et WHtR étaient meilleurs que l'IMC pour la prédiction de l'hypertension chez les adultes de plus de 18 ans. Par conséquent, le WHtR ou le tour de taille est recommandé comme outil de dépistage pour la prédiction de l'hypertension dans nos cliniques, comme moyen de prévention et de détection précoce de l'hypertension pour arrêter ou ralentir l'augmentation du fardeau de l'hypertension. Mots clés: IMC, Hypertension artérielle, Tour de taille, Rapport taillehauteur.

Toxicological evaluation of repeated administration of povidone iodine in cockerels.

Povidone-iodine (Polidine®) is a synthetic broad-spectrum antiseptic being applied topically to treat wounds and prevent their infection. It has been however reported with the assertions that it is effective in the treatment of infectious bursa disease (IBD) when administered orally by practicing Veterinarians and other poultry handlers. Acute kidney injury has been reported also with povidone iodine ingestion. Hence, in this study, graded dose administration was conducted to ascertain its safety profile. Forty chicks were obtained from a poultry hatchery in Ibadan, Oyo State. They were randomly divided into four (4) groups of ten chicks each. Group I served as negative control, groups II, III and IV were administered Polidine® at 1 mL/50 L, 1 mL/25 L, and 1 mL/10 L of water respectively for 7 days. Blood samples were collected on Days 3 and 7 post administration for determination of haematological and biochemical parameters. Liver and Kidney tissues were harvested following termination of the experiment and processed for histopathological examination. Results revealed no significant (p > 0.05) effect in the haematological and biochemical parameters of cockerels treated with Povidone iodine at 1 mL/50 and 25 L of water. On histopathological examination no lesion was also observed in the liver and kidney tissues of groups I, II and III (normal control, 1 mL/50 and 25 L respectively) when compared to group IV (1 mL PI /50 L of water) where lesions were recorded. Hence, this study has shown the relative safety of povidone iodine at different doses in cockerels.

Trypanosuppressive effects of Kolaviron may be associated with down regulation of Trypanothione reductase in Trypanosoma congolense infection.

Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211µM and 0.151µM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64µg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86µg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.

Research Note: Evaluation of acute oral toxicity of povidone-iodine in cockerels using the up-and-down procedure.

Povidone-iodine (Polidine) is a synthetic broad-spectrum antiseptic and being applied topically to treat wounds and prevent their infection. It is however used by poultry farmers, field veterinarians, and other animal health workers with the claim that it is effective for treatment of infectious bursal disease when administered orally. Hence, an acute oral toxicity study was conducted to ascertain its safety profile. Ten cockerel chicks were randomly selected and divided into 2 groups of 5 chicks per group. One group served as the negative control, whereas the other group was administered povidone-iodine at a dose of 2,000 mg/kg of BW orally. The blood sample was collected at the end of the study to determine changes in hematological and biochemical parameters. In addition, vital organs were also harvested and preserved for histopathological examinations. The result showed that the median lethal dose (LD50) of the povidone-iodine is higher than 2,000 mg/kg of BW in cockerels. There were no significant changes in the hematological parameters measured. Biochemical evaluation (renal and liver function test) showed an increase in aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels after administration of povidone-iodine. The study indicated that the LD50 of povidone-iodine is higher than 2,000 mg/kg of BW of cockerels, and there were increases in urinary and liver enzymes at this dose.

Trypanosuppressive effects of Kolaviron may be associated with down regulation of Trypanothione reductase in Trypanosoma congolense infection

@#Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211μM and 0.151μM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64μg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86μg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.

Antimycoplasmal activity of some plant species from northern Nigeria compared to the currently used therapeutic agent.

CONTEXT: Mycoplasma spp. are obligate parasites of humans and animals. But due to the special requirements needed to culture Mycoplasma in the laboratory, little or no research has been done to evaluate the efficacy of medicinal plants on the organism. OBJECTIVE: To screen medicinal plants traditionally used to treat infections for possible antimycoplasmal and cytotoxic activities. MATERIALS AND METHODS: Acetone extracts of 21 Nigerian medicinal plants were analyzed for antimycoplasmal and cytotoxicity activities using the metabolic inhibition and colorimetric methods, respectively. The extract with the best antimycoplasmal activities was also analyzed for its phytochemical constituents using the desktop method. RESULTS: Calotropis procera (Aiton) R.Br (Asclepiadaceae) extract had the best antimycoplasmal effect with a minimum inhibitory concentration (MIC) of 80 µg/mL and minimum mycoplasmacidal concentration (MMC) of 160 µg/mL. This extract contained saponins, tannins, cardiac glycosides, alkaloids, and flavonoids. The extract of Vernonia amygdalina Delile (Compositae) was the most cytotoxic with median lethal concentration (LC(50)) of approximately 17 µg/mL, and that of Anacardium occidentale L. (Anacardiaceae) was the least cytotoxic with an LC(50) of approximately 1919 µg/mL. DISCUSSION: Calotropis procera is a promising plant for an alternative antimycoplasmal agent because the crude acetone extract had a higher mycoplasmacidal activity than the conventional drug tylosin, which is currently used in treatment of the disease in Nigeria. CONCLUSION: The crude extract of Calotropis procera is worth investigating for the development of a potent agent against cattle Mycoplasma, which has long defied solution by conventional chemotherapy.

Toxicological screening of lyophilized extract of some Nigerian wild mushrooms in mice.

Mushrooms are macrofungi widely consumed as food. However, many mushrooms rot away in the wild because of fear of toxicity. Therefore, lyophilized aqueous extracts of 6 mushroom species collected from Zaria, Nigeria and taxonomically identified as Chlorophyllum molybdites, Panaeolus subalteatus, Macrolepiota procera, Leucopaxillus albissmus, Hygrophoropsis aurantiacus and Pholiota aurea were screened for toxicity in mice. Lyophilized aqueous extract of each of these mushrooms was administered to three groups of 3 mice intraperitoneally (i.p.) at doses of 100, 1000 and 10, 000 mg kg(-1), respectively. Another group of three mice given distilled water served as control. The mice were examined for clinical signs of toxicity over a period of 72 h and pathological examinations conducted on dead animals. The severity of clinical signs, onset of death and pathological lesions were dose dependent. Death occurred within 10 min in all the mice dosed at 10,000 mg kg(-1) with the lyophilized extracts of all the mushrooms screened, with the exception of that of H. aurantiacus, which produced death 21-23 h post administration. This result showed that all the screened mushrooms, including the popular edible M. procera were found toxic. Therefore, since all the mushrooms screened were found toxic, it is recommended that extreme caution should be exercised in their consumption. Furthermore, in view of the regional differences in the toxicity of mushrooms, there is the need to screen more wild mushrooms found in Nigeria for toxicity. This will boost mushroom mycophagy, reduce poisoning incidence and reduce wastage of edible mushrooms in the wild.

Experience on Transfontanelle Neurosonography in Kano, Nigeria: a preliminary report.

OBJECTIVE: To retrospectively audit and analyse all the Transfontanelle Neurosonographic scans performed at the Aminu Kano Teaching Hospital (AKTH), between January to September, 2004. METHODS: Information on the gray scale appearance of the ventricles, cerebral and cerebellar parenchyma, extra axial fluid spaces, status of the sulci and gyri and the echogenic internal outline of the bony skull vault was extracted from the records of all the Transfontanelle neurosonographic scans performed at the specialist Ultrasound clinic of the AKTH, between January to September, 2004. RESULTS: Eighteen infants were scanned, and 8 (44.4%) of them were neonates. Meningitis (9 patients) and increasing head size (7 patients) were the commonest clinical indication for referral. Communicating hydrocephalus was the only known complication seen in 4(44.4%) of the post meningitic patients. While in the increasing head size group, congenital malformations such as Aqueductal stenosis and Arachnoid cyst of the quadrigeminal cistern as well as hydrocephalus predominates (4 out of 7 patients). The last 2 patients referred on account of severe birth asphyxia and swollen occiput showed no abnormality and occipital meningocoele respectively. CONCLUSION: This study confirms the earlier notion of the pre-eminence of infection as compared to congenital malformation as the leading cause of infant morbidity in developing nations. It also emphasises the value of Transfontanelle neurosonography as an excellent, non-invasive, inexpensive, rapid and safe imaging modality for the evaluation of the pathologic conditions of infants' brain.

Sequential testicular and epididymal damage in Zebu bulls experimentally infected with Trypanosoma vivax.

Six Zebu bulls aged between 31 and 34 months exhibiting good libido were used to study sequential testicular and epididymal damage in Trypanosoma vivax infection. Three bulls were infected with T. vivax, while the other three served as controls. All infected bulls became parasitaemic by day 5 post-infection and developed clinical trypanosomosis with rapidly developing anaemia. Representative bulls, one from each of the infected and control groups, were sacrificed on days 14, 28 and 56 post-infection. Testes and epididymides from these animals were studied histopathologically after processing and staining with haematoxylin and eosin (H and E). Testicular degeneration developed in all the infected bulls characterized by depletion of spermatogenic cells and destruction of interstitial tissue. The most severe testicular degeneration occurred in the bull that was sacrificed 56 days post-infection. Epididymal sperm reserves were 36%, 4% and 0%, respectively, in infected bulls that were sacrificed on days 14, 28 and 56 post-infection. The 0% epididymal sperm reserve may suggest complete cessation of spermatogenesis. It was concluded from this study that T. vivax infection of Zebu bulls could cause severe testicular and epididymal damage that may result in infertility or even sterility of the affected animals at early infection stages not previously thought.

Excitability scores of goats administered ascorbic acid and transported during hot-dry conditions.

In this study, we investigated the effect of ascorbic acid (AA) administration on goat excitability due to transportation. Ten goats administered AA (p.o.) at 100 mg/kg of body weight before transportation served as the experimental group, and seven goats administered only 10 ml/kg of sterile water (p.o.) served as controls. Excitability scores were recorded for each goat; when weighed, before, immediately after, and 3 h after 8 h of transportation. A score of one to four was allocated to each goat; higher scores represent greater excitability. Immediately after transportation, excitability scores decreased significantly, especially those of control goats (p < 0.001). At 3 h posttransportation, the excitability scores of animals in the experimental group were not significantly (p > 0.05) different from their pre-transportation normal values, whereas those of control goats were significantly lower (p < 0.01). The correlation i.e. the relationship between excitability score values and percent excitability (percentage of goat with particular excitability score) for different excitability score group 3 h post-transportation was positive and highly significant (p < 0.001), in both experimental and control goats. Our results indicate that road transportation induces considerable stress (depression) in goats as evidenced by a lower excitability score posttransportation. Moreover, the administration of AA pretransportation facilitated the transition from a state of depression to excitation. In conclusion, AA administration to animals prior to transportation may ameliorate the depression often encountered after road transportation.

Typhoid enteric perforation in north western Nigeria.

BACKGROUND: Typhoid perforation is the most important surgical complication of typhoid enteritis and is associated with high morbidity and mortality. AIMS AND OBJECTIVES: To determine the pattern and outcome of management of typhoid perforation in Aminu Kano University Teaching Hospital, Kano. METHOD: A retrospective Analysis of patients treated for typhoid perforation over a 6-year period. RESULTS: There were 47 patients: 35 males and 12 females, ratio 2.9 to 1. The patients were aged 4 years to 58 years (mean 18.9 years). Typhoid perforation occurred all the year round with a peak prevalence in September; Six (12.8%) patients perforated in the first week, 29 (61.7%) second week, and 12 (25.5%) third week, of illness. Single perforation was found in 91.5% of cases, and two to three perforations in 8.5%. Surgical treatment was by simple closure in 72.3%, wedge resection in 8.5%, ileal resection in 17.1% and right hemi-colectomy in 2.1%. Of the 41 survivors (87.2%), wound infection was the most common postoperative complication in 44.7% of cases. The mortality rate was 12.8% mostly due to overwhelming sepsis. CONCLUSION: Typhoid perforation requiring surgical intervention is still endemic in our subregion, and emphasis should be on preventive measures such as safe drinking water and appropriate sewage disposal, and typhoid vaccination.

Giant fibrolipomatous polyp of the oesophagus: a case report.

Giant pedunculated oesophageal polyps are rare intraluminal tumours which are usually benign. they include fibrovascular polyp, liposarcoma, harmatomas and lipomas. They may be asymptomatic for a long time and thus attain an enormous size. We present one of such cases of giant oesophageal polyp in a 28 year-old man with a history of difficulty in breathing and vocalisation, easy fatigability and cough. Dysphagia was late in the complaint and he also had lost 7 kg in the last six months before his presentation. A chest radiograph, barium swallow and oesophagoscopy gave the clinical diagnosis. The thoracic CT examination gave a better delineation of the site of the pedicle, the nature and extent of the tumour mass. The tumour was surgically removed and the final pathological diagnosis was afibro-lipoma of the oesophagus. The patient has since been discharged to follow-up in the Surgical out-patient.

Pharmacokinetics of diminazene in plasma and lymph of goats.

OBJECTIVE: To characterize the pharmacokinetics of diminazene in plasma and pseudo-afferent lymph of East Africa X Galla goats. DESIGN: The efferent prescapular lymphatic duct of 3 goats was cannulated 8 weeks after surgical removal of the lymph node. Thereafter, 3.5 mg of diminazene base/ kg of body weight was administered to these goats and to 3 noncannulated goats. PROCEDURE: Using high-performance liquid chromatography, concentration of diminazene was determined in plasma and lymph collected up to 96 hours after treatment. RESULTS: Maximal concentrations of diminazene in plasma of noncannulated goats (median [range], 4.30 [4.28 to 5.01] micrograms/ml), plasma of cannulated goats (3.94 [2.94 to 4.06] micrograms/ml), and lymph (1.06¿0.73 to 1.86] micrograms/ml) were significantly different (P < 0.05); values in lymph were considerably lower than those in plasma from noncannulated and cannulated animals. Time to reach maximal concentration did not differ significantly between lymph and plasma of noncannulated and cannulated goats. Over the first 24 hours after drug administration, concentration of diminazene in plasma of noncannulated goats was generally higher than that in lymph, but thereafter was similar. Apparent volume of distribution of diminazene in the plasma of noncannulated (2.57 [1.93 to 2.60] L/kg) and cannulated (2.30 [1.04 to 2.40] L/kg goats did not differ significantly. Penetration ratio of diminazene into lymph, compared with plasma, of cannulated goats was 1.69:1. CONCLUSIONS: Disposition of diminazene in goats is characterized by higher concentration in plasma than in lymph. However, the drug persists longer in lymph than in plasma. CLINICAL RELEVANCE: The longer persistence of diminazene in lymph than in plasma may account for the enhanced therapeutic efficacy of diminazene in the early stage, compared with later stages, of a tsetse fly-transmitted trypanosome infection.

Frequency of diminazene-resistant trypanosomes in populations of Trypanosoma congolense arising in infected animals following treatment with diminazene aceturate.

The frequency of trypanosomes resistant to diminazene aceturate at a dose of 25 mg/kg of body weight was investigated for populations of Trypanosoma congolense IL 3274 which reappeared in infected mice after intraperitoneal treatment with diminazene aceturate at the same dosage. At inoculum sizes of 10(2), 10(3), 10(4), 10(5), and 10(6) trypanosomes per mouse, the relapse populations were used to initiate infections in five groups of 100 mice each by the intravenous route. Immediately after infection, 50 mice in each group were treated intraperitoneally with diminazene aceturate at the aforementioned dosage; the other 50 mice functioned as untreated controls. Thereafter, all animals were monitored for 100 days for the presence of trypanosomes. In each group, trypanosomes were detected in 50 of 50 control mice, indicating 100% infectivity for all five inoculum sizes. In contrast, in the groups of 50 mice infected with 10(2), 10(3), 10(4), 10(5) and 10(6) trypanosomes and treated with diminazene aceturate, trypanosomes were detected in 4, 11, 13, 28, and 39 of 50 mice, respectively. By logistic regression, a good fit was found between the number of mice identified as parasitemic and the inoculum sizes. Maximum likelihood estimates for the proportions of trypanosomes resistant to diminazene aceturate at 25 mg/kg of body weight for the inoculum of 10(2), 10(3), 10(4), 10(5), and 10(6) organisms were 8.335 x 10(-4), 2.485 x 10(-4), 3.02 x 10(-5), 8.3 x 10(-6), and 1.6 x 10(-6), respectively. These finding indicate that the majority of the relapse trypanosomes were susceptible the the drug dosage used for selecting the population and that, surprisingly, the calculated proportion of organisms which survived drug exposure varied inversely with the inoculum size. Further experiments with mice indicated that the inverse relationship did not result from alterations in the pharmacokinetics of the drug with different inoculum sizes. The data therefore suggest that parasite inoculum size and drug dosage are important factors in estimating the apparent frequency of diminazene-resistant trypanosomes in populations of T. congolense occurring in vivo.

Apparent rarity of diminazene-resistant trypanosomes in goats infected with a diminazene-resistant population of Trypanosoma congolense.

Experiments were carried out in goats to determine the frequency with which diminazene-resistant trypanosomes occur in parasite populations before and after the intramuscular treatment of the goats with diminazene aceturate. Trypanosoma congolense IL 3274, a diminazene-resistant clone, was used to initiate infections in three groups of five goats. The goats in the first group were treated with diminazene aceturate at a dose of 7.0 mg kg-1 bodyweight within 10 seconds of infection; one of the goats was cured. All of the second group, which received no treatment, became parasitaemic. The third group of goats received the same dose of drug as the first group but three days after all of them were first detected parasitaemic; trypanosomes reappeared in all the five goats. When this third group was treated, the frequency of trypanosomes resistant to the drug dosage was estimated to be less than 1 in 10(3). The parasites which reappeared after the treatment of these animals were used to infect two additional groups of five goats intravenously. The goats in one group were treated with the same dose of drug as before, within 10 seconds of infection and were all cured. In contrast, the five goats in the second, untreated, group became parasitaemic. Finally, when the goats in which the infections had relapsed were retreated with diminazene aceturate at the same dose rate, the level of parasitaemia temporarily decreased by at least 10(3) trypanosomes ml-1. These findings suggest that diminazene-resistant T congolense occur at low levels in trypanosome populations despite attempts to select for a population resistant to the dose of drug used.

A simple method for repeated sampling of lumbar cerebrospinal fluid in goats.

A technique has been developed for repeated sampling of cerebrospinal fluid from conscious goats by means of a catheter placed surgically in the subarachnoid space between the sixth and seventh lumbar vertebrae. Uncontaminated cerebrospinal fluid in excess of 1.0 ml could be obtained readily from the cannulated goats several times daily for up to 6 weeks. Cannulated goats did not appear stressed during, and in between, sampling periods.

Pharmacokinetics of diminazene in plasma and cerebrospinal fluid of goats.

The pharmacokinetics of diminazene in the cerebrospinal fluid (CSF) and plasma of five uninfected goats treated with single intramuscular doses of 3.5 mg diminazene base kg-1 bodyweight was investigated. The concentrations of the drug were determined by high performance liquid chromatography, and were three to four times lower in CSF than in plasma. The kinetics of the drug in CSF and plasma differed significantly with respect to Cmax, tmax, AUC0-48h, AUMC0-48h, Cl and Vd(ss).