Clinical effects and pharmacokinetics of different dosage schedules of adriamycin.

Adriamycin was administered to 60 adults and 21 children by 3 different dosage schedules: 22.5 mg/sq m (0.6 mg/kg) daily for 4 days, 15 mg/sq m (0.4 mg/kg) every 8 hr for a total of 6 doses, and 50 to 120 mg/sq m as a single dose every 3 to 4 weeks. Objective responses lasting more than 1 month occurred in 5 subjects with acute leukemias or lymphoma, 3 with transitional cell carcinomas, 2 with sarcomas, 2 with Ewing's sarcoma and 1 each with bronchogenic carcinoma, orchidoblastoma, and thymoma. Toxic reactions included nausea, vomiting, stomatitis, alopecia, and hematopoietic depression, but significant cardiac toxicity occurred in only 1 patient. Pharmacokinetic data, collected in 25 patients by fluorometric and chromatographic assay, suggested a biphasic plasma clearance of drug with initial and secondary half-lives of about 1.5 and 14 to 21 hr, respectively. When drug was given every 8 hr there was evidence of loss of an initial very rapid phase of distribution of adriamycin and its metabolites. Urinary excretion accounted for 3.4 to 38.1% of administered fluorescence over a 72-hr period; in the first 24 hr, between 48.2 and 100% of this urinary material was in the form of adriamycin; leter, this fraction declined. No adriamycin or its fluorescent metabolites could be extracted from the stools.

Refractory metastatic breast cancer: salvage therapy with fluorouracil and high-dose continuous infusion leucovorin calcium.

Sixty women with metastatic breast cancer refractory to at least one chemotherapeutic regimen were treated with fluorouracil (FUra) and high-dose continuous infusion folinic acid (leucovorin calcium). One complete remission lasting 8.7 months and nine partial remissions ranging in duration from 1.3 to 12.8 months were observed, for an objective response rate of 17% (95% confidence interval for response, 8% to 27%). Nine of the ten responding patients had metastatic disease that had objectively progressed on previous chemotherapy with a FUra-containing regimen. This program was well tolerated, with toxicities consisting mainly of stomatitis and granulocytopenia. These results suggest that augmentation of the reduced folate levels of metastatic breast carcinomas may enhance the effectiveness of the fluoropyrimidines in this disease.

Bacteriological study of cooked ogi (fermented cereal weaning food) and its potential safety in a rural Nigerian community.

Thirty households with children receiving the fermented cereal food ogi were selected randomly from Ajara, a rural community in Lagos State, Nigeria. Eighty-one samples of ogi were collected from these households at the time of administration to the children. The degree of bacteriological contamination and pH values of the cooked ogi samples were determined. The mean pH was 3.6 +/- 0.2. Faecal coliform contamination levels of 3 to > or = 2400/ml were recorded in 26 (31.3%) of the 81 ogi samples. Levels of faecal coliforms increased significantly (P < 0.025) during storage of cooked samples for 9 h. The high contamination rate is unacceptable and is a potential health hazard. Although fermenting food like ogi, resulting in a low pH, may reduce bacterial contamination, hygienic practices during handling and preparation should be emphasized as adjuncts in intervention for control of diarrhoeal disease in developing countries.

Combination chemotherapy with cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP) for squamous cancers of the upper aerodigestive tract.

Based on the demonstration of in vitro and in vivo synergy between cytosine arabinoside (Ara-C) and cis-diamminedichloroplatinum (CDDP), we designed a Phase II trial of Ara-C plus CDDP for patients with advanced squamous cancers of the head and neck and esophagus. Sixteen patients were treated on a unique schedule of continuous-infusion Ara-C, 30 mg/m2/day over 72 h, plus CDDP, 30 mg/m2/day at hours 12, 36, and 60 of the Ara-C infusion. The objective response rate was 38% (95% confidence limits 14-62%), with two patients achieving complete clinical and radiographic response (9 and 27+ months duration) and four partial responses (median duration 4 months, range 1-7 months). There was no CDDP-related nephro- or neurotoxicities, but a flu-like syndrome of anorexia and asthenia was common. Myelosuppression was the dose-limiting toxicity, necessitating Ara-C dose adjustments in 11 cycles of therapy and leading to fatal sepsis in one patient. We conclude that the activity of this combination, though comparable to that of other CDDP-containing regimens, offers no significant therapeutic advantage, and given the excessive hematologic toxicity, should not be investigated further.

Wife battering in Nigeria.

OBJECTIVE: To determine the prevalence, types and regularity of spouse abuse among Nigerian women. The effects of socio-economic status, education and alcohol consumption were also investigated. METHOD: Questionnaire survey of 1000 randomly chosen Nigerian women was undertaken. RESULT: Wife abuse was found to be as prevalent in Nigeria as in other parts of the world, 81.0% of the respondents had suffered either verbal abuse (68.6%) or both physical and verbal abuse (31.4%); occasionally (77.4%), regularly (16.2%) or always (6.0%), Almost half of them (46.2%) were abused in the presence of their children. Education and occupation were found to influence the prevalence, type and regularity of abuse and their children witnessing the abuse. CONCLUSION: Wife battering has been found to be very prevalent in Nigeria. However, further research is needed to identify the causes and the psychological effects on these women and their children. This information will be invaluable for designing appropriate medico-social rehabilitation for them.

Sexual activity, contraceptive practice and abortion among adolescents in Lagos, Nigeria.

Nine hundred fifty randomly selected secondary school girls were surveyed. Sexual activity was claimed by 29%, the youngest age was 12 years and age had no influence on the frequency of sexual intercourse. Multiple sexual partners, a high risk behaviour for contracting STD including AIDS was demonstrated in 33.7% and only 20.3% used orthodox methods of contraception. Induced abortion was procured by 23.5% and most were procured from unskilled personnel and by dangerous methods.

Marital disruption--the welfare of the children thereafter in Nigeria.

Departure from the traditional society is being witnessed in Nigeria and many cultural values and control are being lost. Many marriages are contracted between the individuals as opposed to between families, and so poorly withstand the test of time and stress of modern day living, hence more children witness family disruption than before. One thousand randomly selected State Social Welfare case records were studied in depth and information regarding the socioeconomic and demographic characteristics of the families, the nature of their problems, welfare status of the children including paternal contribution for their maintenance were extracted, collated and analyzed. Some important variables were also cross-tabulated. Young maternal age was found to statistically influence the type of case/nature of complaint and the living arrangement of the children (p = .001 and p = .00035 respectively). Income level of the mother also affected the type of case/nature of complaint significantly (p = .00001). About 53.6% of the cases were for maintenance and 23.1% for custody. Most of the children were underage; 56.8% of the first born were under 5 years of age. Single custody was commonly practiced, 63.6% of the children lived with their mothers only and 10.2% with their fathers only before intervention, thereafter 16 of those living with their mothers only were transferred to their fathers. Only .09% of the women remarried and about half of these women had children from their previous marriages living with them; some had their new husbands helping with maintenance. Many of the biological fathers were not responsible for the maintenance of their children and the few that were defaulted regularly. The mothers had to seek redress; the steps taken included social welfare intervention (95.5%), police and legal (4%), and family intervention (0.3%). The inadequacy, inappropriateness, and obsolete nature of our social laws were highlighted by this study. Therefore, urgent attempts at revising and reforming them in line with the demands of the society vis-à-vis our level of development and improving standards of living are strongly recommended.

Epidemiologic survey of menstrual patterns amongst adolescents in Nigeria.

Nine hundred and fifty secondary school girls aged between 10 and 18 years were randomly selected and surveyed. Information on their age at menarche, regularity of menstruation at onset and the time of survey and length of period of irregularity were sought using a well structured questionnaire. Estimation of blood loss per period premenstrual symptoms and signs, prevalence and severity of dysmenorrhoea were also inquired about. This study demonstrated a secular trend in the age at menarche when compared with other similar studies conducted in the previous decade in Nigeria. A higher prevalence of 71.8% of any grade of dysmenorrhoea was found in this study when compared with figures from developed countries, this and the short mean duration of irregular menstruation (3.7 months after menarche) were taken to be evidence of early establishment of regular ovular menstruation.

A study on female circumcision in Nigeria.

A total of 181 women were randomly chosen from the women attending the family planning clinic of the Department of Community Health, College of Medicine, University of Lagos, from February 1984 to September 1984. Of these, 84.7% were aged between 25 and 44 years and most of them are Yorubas (70.7%). A high proportion (56.4%) claimed to have been circumcised but examination revealed that 24.5% had no clinical evidence of circumcision. The Edo tribe had the highest proportion circumcised amongst the respondents, 76.7%, followed by the Ibos, 61%, and least of all the Efiks, 20%. Age at circumcision revealed that most had their circumcision as infants (78.8%) and only 5.9% had theirs as adults, however, the Ibos and Yorubas had high rates of infant circumcision. Some of the respondents were aware of the associated side effects and it was found that the more educated women were less likely to circumcise their daughters. All circumcised daughters were from circumcised mothers except one and she had to circumcise her daughter in conformity with her husband's tribal practice. Accurate statistics of morbidity and mortality from female circumcision will be difficult to gather as circumcision is performed mostly in the houses, nevertheless, the complications are severe enough to merit authoritative intervention. It is recommended that public awareness of female circumcision, its complications and other attendant health hazards should be embarked upon by health authorities especially amongst the tribes practising it.

PIP: A total of 181 women were randomly chosen from the women attending the family planning clinic of the Department of Community Health, College of Medicine, University of Lagos, from February-September 1984. Of these, 84.7% were between 25-44 years of age and most of them were Yorubas (70.7%). A high proportion (56.4%) claimed to have been circumcised by examination revealed that 24.5% had no clinical evidence of circumcision. The Edo tribe had the highest proportion circumcised among the respondents, 76.75 followed by the Ibos, 61% and lastly the Efiks, 20%. Age at circumcision revealed that most had their circumcision as infants (78.8%) and only 5.9% has theirs when adult; the Ibos and Yorubas had the highest rates of infant circumcision. Some of the respondents were aware of the associated side effects and it was found that the more educated women were less likely to circumcise their daughters. All circumcised daughters were from circumcised mothers with the exception of 1 and she circumcised her daughter in conformity with her husband's tribal practice. Accurate statistics of morbidity and mortality from female circumcision will be difficult to gather as circumcision is performed mostly in the houses. Nevertheless, complications are severe enough to merit authoritative intervention. It is recommended that public awareness of female circumcision, its complications, and other attendant health hazards should be issues dealt with by health authorities, especially among the tribes who practice it. (author's modified)

Ethnographic study on childhood diarrhoeal diseases in a rural Nigerian community.

Mothers in thirty households in a rural Nigerian community were subjected to ethnographic studies on food handling practices as they relate to diarrhoeal diseases in children. The study had a first phase of three open-ended unstructured interviews each lasting about 2 hours and a second phase of direct observations on food handling practices during preparation, administration and storage by mothers. Results indicated that as many as 20 (66.7%) of the mothers identified diarrhoea as a common cause of childhood diseases. Diarrhoea due to food contamination was recognized by as many as 18 (60.0%) respondents. Four important food handling practices relating to water treatment, handwashing before preparation and feeding, administration and storage were recognized in the first phase but the claimed practices in the first phase differed significantly from the observed practices in the second phase (p < 0.025). Many (32.1%) mothers had contaminating food handling behaviours. The low literacy level, poverty and lack of good personal hygiene among the studies population were the most likely causes of the behaviours observed.

Adolescents AIDS knowledge, attitude and beliefs about preventive practices in Nigeria.

Three hundred ninety-eight randomly selected Nigerian adolescents were surveyed using well structured questionnaires to collect all information on their knowledge, attitude, beliefs and practice regarding AIDS. The questionnaires were carefully administered and analysed. Most of the respondents, aged 10-20 years, were born in metropolitan cities (83.9%), grew up in such cities (93.2%) and have always lived in them (92.7%). Only 37.9% of them knew the causative agent of AIDS, although 96% claimed to have heard of the disease called AIDS. Seventeen percent (17%) knew all the important routes of transmission and 19.1% identified the groups at high risk for contracting AIDS. Limited knowledge and practice of preventive measures were demonstrated. AIDS was identified as a serious health problem for the world but not yet for Nigeria. Nigerian urban youths have been found to be sexually active with multiple sexual partners. Their knowledge of AIDS is limited, and few of them practice preventive measures. They should, thus, be regarded as a high risk group. Coordinated health education programmes coupled with communication and involvement of these youths should be urgently undertaken.

PIP: 398 adolescents from 8 secondary schools in Lagos, Nigeria were surveyed to assess their knowledge, attitudes, beliefs, and practices of preventive measures in terms of AIDS and to evaluate AIDS education efforts. None of the students thought AIDS was a serious health problem in Nigeria, but 84.2% thought it was the most serious health problem in the world. 96% were aware of AIDS, yet just 37.9% knew that it is caused by a virus. Only 17.1% knew that sexual intercourse, blood transfusions, and mother to child were 3 transmission routes for AIDS. In fact, more students (21.8%) did not know any route. Just 19.1% knew that prostitutes, homosexuals, and drug abusers were groups at high risk of acquiring AIDS, and most teenagers (34.7%) could not identify any high risk groups. Only .7% (3) realized using condoms could prevent AIDS, but 73% (111) of the 152 students who said family planning methods could prevent AIDS mentioned condoms as an AIDS prevention method. 64.1% thought that changes in behavior or life style can prevent AIDS, yet 20% of these students did not know what changes needed to be done to prevent AIDS. 40.7% of the teenagers said they had changed their life style or some behaviors once they heard about AIDS. The main change was not having sexual intercourse with prostitutes. 52.3% believed they would never get AIDS. 33.2% of the students did not list a source of information on AIDS. 41.7% received information from the mass media, especially television and newspapers/periodicals. To effect behavior and life style changes, public health professionals should plan information, education, and communication programs on AIDS which provide accurate information to correct misconceptions and to promote prevention practices.

Assessment of post-vaccination tuberculin sensitivity in Lagos-Nigeria.

An increase in the number of cases of tuberculosis, especially in children, has been observed recently. Post-vaccination conversion rate in babies immunised with BCG was assessed. Sensitization was detected as early as 4 weeks after BCG inoculation. Although 84.2% had physical evidence of BCG inoculation only 69.8% had developed detectable sensitization to the tubercle bacilli as shown by the Mantoux test.

AIDS: awareness and blood handling practices of health care workers in Lagos, Nigeria.

A questionnaire survey of 260 health care workers from 13 randomly selected health care facilities was undertaken. Their knowledge, attitude, belief and blood handling practices regarding HIV/AIDS were enquired about. Virtually all (99.0%) respondents had heard about AIDS but only 57.0% had seen an AIDS patient before. Although 83.0% knew that AIDS is caused by a virus, a high proportion still confuses mode of transmission with causative agent. Deficient knowledge was exhibited when asked about groups of people who were at a higher risk of contracting HIV and AIDS: Only 54.6% and 51.5% identified homosexuals and i.v. drug users as being at a higher risk. Almost all (97.0%) of our respondents claimed to have been more careful in their blood handling practices since the emergence of AIDS, 68.5% wore gloves for all procedures involving handling of blood and 28.5% sometimes although as many as 30.4%, 40.4% and 18.1% do not wear gloves for cleaning up blood stained materials, nursing procedures and taking obstetric delivery respectively. It was evident from their responses that not all the health workers knew the correct method for disposing of used bloodstained instruments and left-over blood samples and neither were they all adhering to the safety guidelines recommended for handling these materials. Education of all health care workers in Nigeria on the Universal Precautions Guidelines issued by the Centers for Disease Control (CDC) in 1987 regarding blood, body fluids and contaminated instruments' handling precautions is urgently recommended.

Combination chemotherapy with cyclophosphamide (NSC-26271), cytosine arabinoside (NSC-63878), and methotrexate (NSC-740) in advanced solid tumors.

Forty patients with advanced solid tumors of diverse primary sites received a combination of cyclophosphamide (1 gm/m2), cytosine arabinoside (300 mg/m2), and methotrexate (80 mg/m2) given intermittently at 2-3-week intervals. Eight of the 40 patients received citrovorum factor rescue. The major limitation of therapy was suppression of bone marrow elements. Only minimal nonhematologic toxicity was encountered. Granulocytes appeared the most sensitive. The first course of treatment produced median nadir granulocyte and platelet counts of 1200 and 100,000 cells/mm3 respectively. Subsequent courses were tolerated with no evidence of increasing myelosuppression. Objective antitumor responses were noted in five of 16 patients with lung cancer and in eight of 14 women with breast cancer with a median duration of 8 months.

Study on the pH of ogi, Nigerian fermented weaning food, and its effect on enteropathogenic Escherichia coli, Salmonella typhi and Salmonella paratyphi.

The pH values of both cooked and uncooked ogi samples were determined and the survival of nalidixic acid-resistant enteropathogenic Escherichia coli OB 26 34/20, Salmonella typhi and Salmonella paratyphi A when seeded into cooked ogi were studied. The pH values of ogi ranged from pH 3.0 to 3.9. Cooked ogi had a slightly lower pH value than uncooked ogi. Our survival experiments showed that the inoculated enteric pathogens were considerably inhibited in cooked ogi during storage for 24 h. The antibacterial effect of cooked ogi was more pronounced on enteropathogenic E. coli with a log10 5 decline in bacterial count within 6 h.

Treatment of metastatic malignant melanoma with trimetrexate: a phase II study.

Trimetrexate glucuronate, a nonclassical antifolate, was administered to 14 patients with recurrent and progressive metastatic malignant melanoma. Thirteen patients were evaluable for response and toxicity. Five patients had received prior treatment consisting of immunotherapy (one patient), immunotherapy plus radiotherapy (one patient), radiotherapy (one patient), chemotherapy (one patient), or radiotherapy and chemotherapy (one patient). The starting dose of trimetrexate was 8 mg/m2 given as an intravenous bolus daily for 5 consecutive days of a 21-day cycle. Subsequent cycles of therapy were escalated by 25% based on individual patient tolerance. A median of two courses of trimetrexate was administered (range 1-4). No patient demonstrated a measurable objective response to this treatment regimen. Trimetrexate was well-tolerated; toxicity was mild and consisted primarily of myelosuppression or nausea and vomiting. At the dose level and schedule used in this study, trimetrexate was not effective for the treatment of disseminated malignant melanoma.

3-Deazaguanine: report of a phase I trial and drug-related cardiac toxicity.

3-Deazaguanine (Dezaguanine), a purine antimetabolite, was evaluated in a phase I trial in 42 patients with advanced solid tumors. Dezaguanine was given as a weekly intravenous infusion for three consecutive weeks of a four-week cycle. The dose ranged from 30 to 2000 mg/m2; no consistent dose-limiting hematologic or gastrointestinal toxicity was observed. Some patients reported brief episodes of burning at the infusion site or transient facial flushing immediately following the administration of dezaguanine. Three patients experienced cardiac toxicity. Two patients, at doses of 1130 and 2000 mg/m2 respectively, developed congestive heart failure. In one case the heart failure was fatal; the second patient recovered within 8 weeks. The third patient had a progressive fall in left ventricular ejection fraction but did not develop clinical evidence of heart failure before his death from progressive cancer two months later. Postmortem cardiac pathology in the two patients who died early following therapy revealed nonspecific interstitial fibrosis without inflammatory cell infiltrates. The myocardium of the third patient, who died 20 months after receiving dezaguanine, was normal. Electron microscopic analysis of myocardium from the first patient did not show myofibrillar loss or mitochondrial disorganization characteristic of anthracycline cardiomyopathy. Due to the probable cardiotoxicity of dezaguanine in this study and the lack of objective antitumor response, further development of this agent has been discontinued.