Further studies to evaluate methods of leucoreduction to prevent alloimmune platelet refractoriness and induce tolerance in a dog platelet transfusion model.

OBJECTIVES: Three leucoreduction filters were evaluated - when used alone or combined with centrifuge leucoreduction (C-LR) - to prevent alloimmune platelet refractoriness in a dog platelet transfusion model. MATERIALS AND METHODS: Donor platelet-rich plasma (PRP) or buffy coat (BC) platelets were either filter leucoreduced (F-LR) or F-LR/C-LR, (51) Cr radiolabelled and transfused. Weekly transfusions were given for up to 8 weeks or until platelet refractoriness. Recipients who accepted treated transfusions were then given non-leucoreduced (non-LR) platelets to determine whether donor-specific tolerance had been induced. RESULTS: Acceptance of F-LR PRP transfusions ranged from 29% to 66%. F-LR/C-LR transfusions prepared from PRP were accepted by 92%, from BC by 63% and from pooled PRP by 75% of recipients (p=NS); overall acceptance rate of F-LR/C-LR transfusions was 83%. Tolerance to subsequent non-LR transfusions occurred in 45% of the F-LR-/C-LR-accepting recipients unrelated to DR-B compatibility between donors and recipients (P = 0·18). CONCLUSION: In a dog platelet transfusion model, acceptance of donor platelets required combining F-LR with C-LR as apparently each process removes different immunizing WBCs.

Differences in right ventricular-pulmonary vascular coupling and clinical indices between repaired standard tetralogy of Fallot and repaired tetralogy of Fallot with pulmonary atresia.

PURPOSE: The purpose of this study was to compare ventricular vascular coupling ratio (VVCR) between patients with repaired standard tetralogy of Fallot (TOF) and those with repaired TOF-pulmonary atresia (TOF-PA) using cardiovascular magnetic resonance (CMR). MATERIALS AND METHODS: Patients with repaired TOF aged>6 years were prospectively enrolled for same day CMR, echocardiography, and exercise stress test following a standardized protocol. Sanz's method was used to calculate VVCR as right ventricle (RV) end-systolic volume/pulmonary artery stroke volume. Regression analysis was used to examine associations with exercise test parameters, New York Heart Association (NYHA) class, RV size and biventricular systolic function. RESULTS: A total of 248 subjects were included; of these 222 had repaired TOF (group I, 129 males; mean age, 15.9±4.7 [SD] years [range: 8-29 years]) and 26 had repaired TOF-PA (group II, 14 males; mean age, 17.0±6.3 [SD] years [range: 8-29 years]). Mean VVCR for all subjects was 1.54±0.64 [SD] (range: 0.43-3.80). Mean VVCR was significantly greater in the TOF-PA group (1.81±0.75 [SD]; range: 0.78-3.20) than in the standard TOF group (1.51±0.72 [SD]; range: 0.43-3.80) (P=0.03). VVCR was greater in the 68 NYHA class II subjects (1.79±0.66 [SD]; range: 0.75-3.26) compared to the 179 NYHA class I subjects (1.46±0.61 [SD]; range: 0.43-3.80) (P<0.001). CONCLUSION: Non-invasive determination of VVCR using CMR is feasible in children and adolescents. VVCR showed association with NYHA class, and was worse in subjects with repaired TOF-PA compared to those with repaired standard TOF. VVCR shows promise as an indicator of pulmonary artery compliance and cardiovascular performance in this cohort.

Progesterone vaginal ring as a new contraceptive option for lactating mothers: Evidence from a multicenter non-randomized comparative clinical trial in India.

OBJECTIVES: Evaluate and compare contraceptive efficacy, safety, continuation rates and duration of lactational amenorrhea (LA) in married lactating women (20-35 years) using the progesterone vaginal ring (PVR) or Copper-T380A intrauterine device (IUD) during the first postpartum year. STUDY DESIGN: We conducted a one-year multicenter, non-randomized, non-inferiority, open-label, comparative trial at 20 centers in India and compared efficacy, safety, continuation and LA plus feeding patterns and growth/well-being of participants' infants. Women used four 3-month PVRs consecutively (lost PVRs were not replaced) and were to breastfeed at least four times/day. We used Pearl Index (PI) and Kaplan Meier (K-M) rates to analyze pregnancy and K-M for continuation. RESULTS: We enrolled 789 women (459 PVR, 330 IUD). Neither PI nor K-M one-year pregnancy rates differed significantly between groups (PI: PVR-0.62; IUD-0.35); (K-M: PVR-0.7; IUD-0.4, p = 0.58). Continuation rates at 12 months were 78.5% (IUD) vs. 56.9% (PVR) (p < 0.001). Ring expulsions and menorrhagia were the most common discontinuation among PVR/IUD users respectively. The median duration of LA among PVR vs. IUD users was 405 vs. 120 days (p < 0.001). Both groups reported similar adverse events (PVR: 24.2%; IUD: 23.0%); there were no serious adverse events among PVR users. Infants from both groups fed 12-7 times/day and grew at expected rates. CONCLUSIONS: Efficacy and safety outcomes were comparable among women in both groups. Continuation rates for PVR, a woman-controlled method, were shorter than IUD rates while PVR users maintained LA significantly longer than IUD users. Infant breastfeeding and growth patterns/well-being were favorable in both groups. IMPLICATIONS: PVR, a user-controlled device, offers an additional contraceptive choice for lactating women for one-year postpartum use and can help to address the unmet need for contraception among postpartum women while encouraging breastfeeding to enhance infant growth and well-being.

Bladder Carcinoma Associated with BK Virus in a Renal Allograft Recipient.

Bladder carcinoma is a relatively rare carcinoma reported in renal allograft recipients. While many oncogenic viruses have been implicated as causative factors for certain malignancies, questions have been raised about possible role of BK virus in pathogenesis of urothelial cancers. In this report, we have described a patient who developed BK virus nephropathy followed 3 years later by bladder carcinoma. Interestingly, while the tumor tissue demonstrated BK virus, the adjacent normal urothelium was stained negative for BK virus. Considering the viral potential to inhibit tumor suppressors and its differential localization within tumor tissue, it is possible that the virus contributes to tumorigenesis.

Nonoxynol-9 vaginal pessary: a preliminary Indian experience.

BACKGROUND: Barrier methods of contraception do not have systemic effects and allow the user complete control over their use. For women, the ease of use of a contraceptive is often more important than its efficacy. Hence, barrier methods could be offered as a useful alternative method of contraception. Nonoxynol-9 (a spermicide) is a locally acting, non-hormonal method free from systemic side-efforts. It is a woman-controlled, reversible method which is to be used before intercourse. There are little data available on its efficacy, side-effects and acceptability among Indian women. METHODS: The vaginal pessary nonoxynol-9 was offered as a contraceptive option to 3200 women attending the Family Planning clinics at 31 Human Reproduction Research Centres (HRRCs) of the Indian Council of Medical Research. The other contraceptives offered included an intrauterine device, oral pills, condoms, Norplant, tubal sterilization and vasectomy using the cafeteria approach. Those who accepted nonoxynol-9 were followed up to assess the rates of continuation, failure and side-effects. RESULTS: The nonoxynol-9 pessary was accepted by 541 women who were followed up for 3470 woman-months of use. The reasons given for acceptance were that it was user-controlled and/or they did not wish to use other methods because of the side-effects or contraindications of these methods. The overall continuation rates were 41.2% and 33% at 9 and 12 months of use, respectively. Most women (31.3%) discontinued its use due to personal reasons such as husband dissatisfaction, desire for further pregnancy, irregular use of pessary and difficulty in insertion. Twenty-nine women became pregnant during the study period (15 due to method failure and 14 due to user failure) giving a use-effectiveness of 8.8% at 12 months. The method failure rate was 4.3% at 12 months of use. The failure rates were lower compared with the reported failure rates of barrier contraceptives (1%-30% at 1 year of use) and the side-effects were minimal. CONCLUSION: Nonoxynol-9 had low acceptability (16.9%) and overall continuation rates--41.2% and 33% at 9 and 12 months of use. It could be offered to women looking for a short term, user-controlled contraceptive.

Analysis of large-scale nonhuman primate islet isolations.

AIMS: It is important to have clinically relevant large animal models, especially nonhuman primates, to improve the efficacy of islet isolation and transplantation prior to clinical trials. The aim of this study was to improve the efficacy of islet isolation by analyzing large-scale nonhuman primate islet isolations. METHODS: Sixty-one islet isolations were evaluated using nonhuman primates. An automated isolation method was scaled down for islet isolation. Islet yields of prepurification, postpurification, and postculture, purity of islets, viability of islets, and functionality with glucose stimulation test were assessed. Initially, we analyzed relationships between endpoints then analyzed additional factors for successful islet isolation. Those factors included donor characteristics, the two-layer method (TLM) of pancreas preservation, trypsin inhibition during digestion, and digestion and collection time. RESULTS: Prepurification islet yields were strongly correlated with postpurification yields and postculture yields. It weakly but significantly correlated with purity, viability, and functionality. The average prepurification yield was 16,267 IE/g with each case divided into either above-average (high-yield group) or below-average groups (low-yield group). In 8 cases, TLM and trypsin inhibition were used and all cases belonged to the high-yield group. There were no significant differences between high- and low-yield groups in terms of donor age, body weight, pancreas weight, and cold ischemic time. The high-yield group had significantly longer digestion times and shorter collection times. CONCLUSIONS: TLM, trypsin inhibition, complete digestion, and quick collections were key for successful islet isolation. Analysis of nonhuman primate islet isolation techniques provided useful information, which should help to improve clinical islet transplantation.

Immunogenetic analysis suggests different pathogenesis for obese and lean African-Americans with diabetic ketoacidosis.

OBJECTIVE: When presenting with diabetic ketoacidosis (DKA), lean and obese patients differ in their subsequent clinical course. Although lean patients tend to remain insulin dependent, most obese patients recover endogenous insulin secretion and discontinue insulin therapy. The aim of this study was to determine whether obese African-American patients with DKA could be determined to have type 1 or type 2 diabetes based on insulin secretion or the presence of immunological and genetic markers. RESEARCH DESIGN AND METHODS: This was a prospective study that analyzed the clinical characteristics, insulin secretion indices, immunological markers (islet cell, GAD, ICA512, and insulin autoantibodies), and HLA susceptibility genes (DR/DQ) in 131 patients with DKA (77 obese and 54 lean), 51 obese patients with hyperglycemia but no DKA, and 25 nondiabetic subjects. All subjects were African-American. Beta-cell function was evaluated by the C-peptide response to glucagon (1 mg i.v.) within 48 h of resolution of DKA or hyperglycemia. RESULTS: The acute C-peptide response was lower in obese DKA patients (1.0+/-0.1 ng/ml) than in obese patients with hyperglycemia (1.7+/-0.2 ng/ml, P < 0.01), but was higher than that in lean DKA patients (0.2+/-0.1 ng/ml, both P < 0.01). The overall prevalence of autoantibodies in obese subjects with DKA (17%) and obese subjects with hyperglycemia (16%) was lower than that in lean subjects with DKA (65%, P < 0.01). Obese patients with hyperglycemia and positive autoantibodies had lower rates of insulin secretion than those without antibodies. Regardless of body weight, all DKA patients with GAD autoantibodies carried the DQB1*0201 allele. However, there were no significant differences in HLA distribution between the three patient groups. CONCLUSIONS: Our results indicate that most obese African-American patients with DKA have type 2 diabetes characterized by higher insulin secretion, the absence of autoimmune markers, and a lack of HLA genetic association. In contrast, most lean African-American patients with DKA have metabolic and immunological features of type 1 diabetes. At presentation, assessment of beta-cell function and determination of autoimmune markers allow for correct classification of diabetes in African-Americans with hyperglycemic crises.

Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women.

BACKGROUND AND PURPOSE: Although family studies have suggested a genetic influence on hemorrhagic stroke, the underlying genetic risk factors remain poorly defined. Coagulation factor XIII, which is involved in hemostasis, fibrinolysis, vascular remodeling, and tissue repair, represents a candidate gene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding-sequence polymorphisms, along with a promoter polymorphism of plasminogen activator inhibitor-1 (PAI-1, which is also involved in fibrin stabilization and vascular remodeling), in young white women with hemorrhagic stroke. METHODS: Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and for PAI-1 -675 4G/5G was performed in a population-based case-control study of 42 white women aged <45 years with nonfatal hemorrhagic stroke and 345 demographically similar control subjects. RESULTS: Compared with the respective homozygous wild-type genotypes, the Tyr204/Phe204 genotypes (age-adjusted odds ratio [OR] 2.9, 95% 95% CI 1.1 to 7.5) and the Leu564/Leu564 genotype (OR 4.3, 95% CI 1.4 to 13.7) were each associated with an increased risk of nonfatal hemorrhagic stroke. The risk estimate associated with the Phe204 variant was highest in women with subarachnoid hemorrhage and in nonsmokers, whereas the risk estimate of the Leu564/Leu564 genotype was highest in women with intracerebral hemorrhage and in smokers. Women who carried either the Phe204 allele or the Leu564/Leu564 genotype in combination with the PAI-1 5G/5G genotype had a nearly 20-fold increased risk of hemorrhagic stroke (OR 18.9, 95% CI 3.8 to 95.1). CONCLUSIONS: Our findings suggest that the Phe204 and Leu564 variants of coagulation factor XIII may be markers for genetic susceptibility to hemorrhagic stroke in women aged <45 years.

Analysis of platelet glycoprotein Ia (alpha2 integrin) allele frequencies in three North American populations reveals genetic association between nucleotide 807C/T and amino acid 505 Glu/Lys (HPA-5) dimorphisms.

Glycoprotein Ia (alpha2 integrin) is a subunit of the heterodimeric membrane complex (GPIa/IIa) that mediates platelet adhesion to collagen. Several nucleotide sequence variations of GPIa have been described. A nucleotide 1648 G/A dimorphism that leads to a Glu/Lys substitution at amino acid 505 is responsible for the human platelet antigen system, HPA-5. Recently, two other linked GPIa nucleotide dimorphisms involving codons Phe224 and Thr246 were identified: a C/T substitution at nucleotide 807 and a G/A substitution at nucleotide 873(1). Using restriction enzyme digestion of amplified GPIa genomic DNA fragments (PCR-RFLP) to distinguish genotypes, we have determined the allele frequencies of the GPIa 807C/T and Glu/Lys505 dimorphisms in three North American populations, and a panel of non-human primates. Our results indicate a genetic relationship between the 807C/T and Glu/Lys505 dimorphisms that leads to an evolutionary model of GPIa isoforms.

Evolution of HLA class I epitopes defined by murine monoclonal antibodies: distribution in macaques.

Murine anti-HLA monoclonal antibodies (MoAbs) to monomorphic and polymorphic epitopes were compared for their reactivity in humans vs. pigtailed macaques (Macaca nemestrina). Five MoAbs to monomorphic class I epitopes in humans displayed distinct patterns in macaques: two were unreactive, one reacted with 93% of animals tested, another with 17%, and one with only 8% of animals tested. Thus, epitopes that are monomorphic in one species can be highly polymorphic in another. Most of the 23 MoAbs (91%) against polymorphic epitopes in humans also detected polymorphisms in macaques. The epitopes detected by MoAbs could be divided roughly into two groups: epitopes that were expressed at the same frequency in both species, i.e., monomorphic, public, or private epitopes in both species, or epitopes that had quite different expression in the two species, e.g., a "public" epitope in one species expressed as a "private" epitope in the other. The genes encoding some of these polymorphisms were shown to segregate in families and thus some anti-HLA MoAbs are useful typing reagents for macaques. Two MoAbs thought to detect the same specificity in humans were found to react in macaques with different animals. Thus, reactivity patterns of anti-HLA class I MoAbs in primate populations enabled MoAbs to closely associated epitopes to be distinguished.

Increased frequency of HLA class II alleles DRB1*0301 and DQB1*0201 in Lambert-Eaton myasthenic syndrome without associated cancer.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune neuromuscular disorder characterized by pathogenic autoantibodies directed against the presynaptic voltage-gated calcium channels (VGCC), resulting in a clinical syndrome of proximal muscular weakness and autonomic dysfunction. Sixty percent of LEMS cases are associated with cancer, most commonly small cell carcinoma of the lung. In the 40% of LEMS patients without carcinoma, the stimulus for the production of VGCC autoantibodies is unknown; however, these LEMS patients have multiple other organ-specific autoantibodies. To investigate the autoimmune basis of noncancer associated LEMS (NCA-LEMS), high resolution typing of major histocompatibility loci was performed in 23 patients with NCA-LEMS. NCA-LEMS was strongly associated with DRB1*0301 (p<0.0001) and DQB1*0201 (p<0.0001), suggesting that NCA-LEMS is an autoimmune disorder associated with the DR3-DQ2 extended haplotype.

The major histocompatibility complex, MnLA, of pigtailed macaques: definition of fifteen specificities.

The major histocompatibility complex (MHC) of pigtailed macaques (Macaca nemestrina, Mn) is defined and designated as MnLA. Twenty-nine alloantisera were generated by fullsib alloimmunization and tested against a panel of 220 unrelated animals. The reactivities of different alloantisera were analyzed statistically in pairwise comparisons. Using 2 X 2 contingency tables, we calculated chi 2 independence, chi 2 allelism, and correlation coefficient values. Initially, specificities were defined by significant associations of certain sera, but some sera defined specificities individually. In all, 15 specificities were defined, and by family studies and negative correlation coefficients, a two-locus model was evident. Genetic analyses, together with statistical applications, revealed that the behavior of these specificities is consistent with the nature of MHC in other primate species, including man.

Low-dose streptozotocin induces sustained hyperglycemia in Macaca nemestrina.

The potential for using macaques to create a nonhuman primate diabetic model was investigated. The significant objectives were to determine a) prognosis of STZ induced permanent beta cell destruction in nonhuman primates, and b) the potential to use STZ treated animals in a model of autoimmune diabetes by following adoptively transferred lymphocytes into MHC identical macaques. Beta cell impairment was achieved by a single intravenous, low dose (10-40 mg/kg body weight) streptozotocin injection in a majority of pigtailed macaques (Macaca nemestrina). Multiple injections, even at low doses at close intervals affected liver and kidney functions in addition to beta cell destruction. Abnormal IVGTT were observed in all streptozotocin-treated animals, in some within a week to 10 days. The fasting blood glucose levels rose from <70 mg/dl in pre-STZ stage to above 400 mg/dl in severely diabetic macaques. Histological evidence suggests loss of beta cells when animals were euthanized within two to four weeks post-STZ treatment. Near complete destruction of beta cells was observed in animals maintained longer than three months on insulin. Donor T cells from STZ-treated animals were incubated overnight with 10U/ml IL-2 and 2.5 ug/ml PHA and then injected iv into a MHC-identical non-diabetic sibling. Three weeks later a second injection of donor PMBC labeled with vital dye Cell Tracker Green was given and the animal was euthanized after 24 hours. The recipient showed labeled donor T cells in the pancreas, spleen and peripheral blood, consistent with specific homing of activated lymphocytes from the diabetic donor.

Complexity of human immune response profiles for CD4+ T cell epitopes from the diabetes autoantigen GAD65.

Complex protein antigens contain multiple potential T cell recognition epitopes, which are generated through a processing pathway involving partial antigen degradation via proteases, binding to MHC molecules, and display on the APC surface, followed by recognition via the T cell receptor. We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM. Using sets of 20-mer peptides spanning the GAD65 molecule, multiple immunostimulatory epitopes were identified, with diverse class II DR molecules functioning as the restriction element. The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. Antigen-specific T cell clones and lines were derived from peripheral blood samples of pre-diabetic and IDDM patients and T cell recognition and response were measured. Highly variable proliferative and cytokine release profiles were observed, even among T cells specific for a single GAD65 epitope.

Genetic and immunological markers of insulin dependent diabetes in Black Americans.

ICA and GAD65 autoantibody profiles and HLA-DR and DQ analysis were performed on 43 Black juvenile onset IDDM patients and 34 unrelated Black controls from Tennessee, USA. 75% of patients were positive for GAD65 autoantibodies but only 53% had ICA; 39% both ICA and GAD65 antibodies. The strongest HLA association was with the DR3 haplotype DRB1*03 DQA1*0501 DQB1*0201 (63% of patients v 12% of controls RR = 13.0, p < 0.00002). DRB1*04 DQA1*0301 DQB1*0302, associated with IDDM in Caucasians but rare in Negroids, occurred in 27% of patients and 6% of controls (RR = 5.9, p < 0.04). All patients carried DQB1*0302 or DQB1*0201. DQB1*0602 was significantly reduced in patients (2.4% v 41%, RR = 0.036, p < 0.008) and DRB1*1501 was absent in patients (0% v 35%). The frequency of GAD65 autoantibodies in Black American IDDM patients is comparable to that in Caucasians; however ICA positivity is reduced. GAD65 antibodies may therefore be a more sensitive serological test to identify individuals in the Black American general population for markers associated with increased risk of developing IDDM. Current screening methods for predicting preclinical IDDM in Caucasians relies on a combination of immune and HLA markers of IDDM; studies of these markers in the Black Americans will make it possible to extend these options to additional genetically diverse populations.

Inverse relationship between GAD65 antibody levels and severe retinopathy in younger type 1 diabetic patients.

Several risk factors for severe non-proliferative and proliferative retinopathy in type 1 diabetes mellitus have been proposed without explaining the rapid progression of retinopathy in some patients. Since GAD65 autoantibodies (GAD65Abs) are detected against glutamic acid decarboxylase (GAD), which is mainly expressed in islets and nervous tissue in type 1 diabetic patients, the aim of the present investigation was to test the hypothesis whether GAD65Abs are associated with rapidly progressing severe retinopathy. Patients with severe non-proliferative or proliferative retinopathy (n = 27) were compared with another group, which in spite of long diabetes duration had no or only mild signs of retinopathy (n = 28). GAD65Abs were analysed in a radioimmunoassay using in vitro translated human GAD65, and the levels were expressed as an index in relation to positive and negative reference samples. Using a cut-off level representing the 99th percentile of normals, 6/27 (22%) with and 9/28 (32%) without severe retinopathy were considered GAD65Ab positive. Although there was no difference in the number of GAD65Ab positive patients, the GAD65Ab levels were lower in patients with (0.30; 0.11-0.64) than without (0.68; 0.34-1.12) severe retinopathy (P = 0.03). The patients were also subjected to HLA-DR and DQ typing by PCR and hybridization with oligospecific probes. DQ2/8 was more common in patients with (56%) than without (29%) severe retinopathy (P = 0.05), but DQ2/8 could not account for the lower GAD65Ab levels in patients with severe retinopathy. It is concluded that GAD65Ab levels are inversely correlated with severe retinopathy in young type 1 diabetic patients.

Vaginal bleeding patterns of women using different contraceptive methods (implants, injectables, IUDs, oral pills)--an Indian experience. An ICMR Task Force Study. Indian Council of Medical Research.

Irregularity in vaginal bleeding patterns is the most common clinical side effect causing discontinuation of the method reported by the-users of the newer contraceptive methods, especially hormonal ones. An objective assessment of vaginal bleeding pattern is, therefore, critical in evaluation of a new contraceptive method for its acceptance and continued use. The menstrual diary records of women participating in clinical trials of several contraceptive methods undertaken by the Indian Council of Medical Research were analysed. It was observed that the long-acting progestogen-only hormonal contraceptives like levonorgestrel (LNG)-releasing subdermal implants Norplant or intrauterine devices (LNG-IUD) as well as injectable contraceptive NET-EN 200mg given 2 or 3 monthly produced disturbances in bleeding pattern in the majority of their users. Very heavy or prolonged bleeding, a potential health hazard was uncommon and a shift more towards infrequent bleeding was observed. In Norplant-II implants users, 75 to 80% of women had irregularities in bleeding pattern during the first year of use which improved with prolonged use. However, even at 4 years of use, about half of the users of Norplant-II implants continued to have irregular bleeding patterns. The bleeding disturbances occurred in 80% users of 200mg NET-EN injectable contraceptives also during first year of use, however unlike Norplant-II implants users, there was no improvement with prolonged use. Combined monthly injectable contraceptives containing 50mg NET-EN and 5mg estradiol valerate caused less bleeding problems with half of the users experiencing normal pattern during one year of its use. Combined low-dose oral pills, both triphasic and monophasic, produced much better cycle control as compared to any of the other hormonal contraceptive-treated groups; about 90% of combined oral pill users had normal bleeding patterns during one year of method use. The use of copper IUDs was associated with increased bleeding in 18 to 20% of women during the initial period of three months which improved with prolonged use. It was observed that the women having frequent or prolonged bleeding had discontinued the contraceptive method more often as compared to those having delayed bleeding episodes or oligomenorrhoea. However, discontinuation rates due to bleeding irregularities at one year were lower in Norplant-II implants users as compared to other long acting hormonal contraceptive methods such as injectables or IUDs in spite of similar or better bleeding patterns in women using these methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Dynamics of contraceptive practice amongst urban Indian women.

BACKGROUND: Most studies on knowledge, attitude and practice regarding contraceptives have been conducted in rural areas and urban slums. In this study, a mixed urban population was surveyed. SUBJECTS: Two thousand parous women from different social and educational backgrounds residing in the metropolis of Mumbai (Bombay), Maharashtra were included in the study. RESULTS: Fifty per cent of illiterates, semi-literates and highschool educated, and 80% of college-educated couples said that they had no gender preferences for their children, but actual practice belied this. Regardless of the level of education, 25%, 75% and 95% of all couples were sexually active by 6 weeks, 3 months and 6 months after childbirth. Awareness regarding the availability of various contraceptives increased with education; 20% of all graduate couples used condoms or the rhythm method immediately after marriage. After the birth of their first child, 80% of educated couples used spacing methods whereas even after the birth of their third child more than 50% of the uneducated did not. The major complaint of the intrauterine device users was menorrhagia and abdominal pain, while that of pill users was nausea, giddiness and headache. Spacing methods were popular among the educated, and terminal ones among the uneducated. Steroidal contraceptive pills were not popular with any group, regardless of the level of education. CONCLUSION: Education was the main variable in the decisions regarding the family size, spacing interval, contraceptive awareness, its use immediately after marriage and during the postpartum period.