An unusual case of Pseudohypoaldosteronism coexisting with cystic fibrosis.

Pseudohypoaldosteronism type 1 is a rare congenital autosomal recessive disorder, characterised by failure of receptor response to aldosterone. It is caused by mutation in SCNN1A gene with clinical features like failure to thrive in infancy, hyponatraemia, hyperkalaemia and metabolic acidosis. We present a male infant with seizures, hyperkalaemia and with failure to thrive, diagnosed at day 6 of life. The baby required repeated correction for hyperkalaemia; hence, after ruling out treatable causes for hyperkalaemia, exonerated sequencing was done which showed pathogenic mutation for cystic fibrosis and recessive mutation for pseudohypoaldosteronism. But the child was clinically in favour of pseudohypoaldosteronism. Hence, features of pseudohypoaldosteronism predominate cystic fibrosis; they both may coexist.

Microcornea, cerebellar hypoplasia and hyperlax joints-unusual combo in rare Ehlers-Danlos syndrome-musculocontractural type 1.

Ehlers-Danlos syndrome is a group of connective tissue disorders with 14 subtypes, involving joint hyperlaxity, tissue fragility, hypertensive skin and other systemic organs with an incidence of 1 in 1 000 000 worldwide. We report a middle childhood female born of second degree consanguineous marriage with limping gait with muscle weakness, with normal development and IQ. Examination revealed microcornea, distal joint laxity of fingers and wrist, hypotonia and broad-based limping gait. Fracture dislocation right hip was managed by fixation. With the atypical neuroimaging finding of cerebellar vermis hypoplasia, exome sequencing was ordered and confirmed as Ehlers-Danlos syndrome (musculocontractural type-1). Hence, genetic counselling was done and prognosis of the child was explained.

Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Assessment of behavioural problems in preschool and school going children with epilepsy.

Introduction: Children with epilepsy are at greater risk of developing psychiatric and behavioural disorders such as attention deficit/hyperactivity disorder (ADHD), conduct disorder, autism spectrum disorder (ASD), as well as affective and aggressive disorders than normal children which may affect the well- being and quality of life of the child. Aim and Objectives: This study aims at identifying behavioural problems in children with epilepsy enabling early diagnosis and intervention. The objectives were to assess the presence and type of behavioural problems in children with epilepsy. Methods: A prospective cross-sectional study was conducted on children who were diagnosed as epilepsy in two age groups of 1.5-5 years and 6-18 years recruited by non-probability convenience sampling. Data regarding seizure semiology, clinical features and treatment were obtained. Children underwent IQ assessment, electroencephalogram and brain neuroimaging. Child Behaviour Check List (CBCL) was administered to parents or primary caregivers after obtaining informed consent. Results were analyzed for presence of behavioural problems using SPSS-23. Results: In the study, out of 50 study subjects, 72% were between 6-18 years. 60% children had generalised seizures, 58% children had epilepsy for <2 years and abnormal EEG was present in 80% children. 6% children had behavioural problems and 4% had borderline presentations. Co-relation of behavioural problems with age was statistically significant with p value 0.027. Behavioural problems identified were aggressiveness and anxiety. Conclusion: Childhood epilepsy is associated with behavioural problems along with other co-morbidities warranting a search during follow-up visits. Take-home message: Early identification and treatment of behavioural problems in children with epilepsy by periodic assessment during follow up visits, careful selection of combination of drugs and appropriate dose can improve the overall outcome in children taking antiepileptic drugs (AEDs) for epilepsy.

Lightning Characteristics Over Humid Regions and Arid Regions and Their Association With Aerosols Over Northern India.

The association between aerosol and lightning has been investigated with long-term decadal data (2005-2014) for lightning, aerosol optical depth (AOD), relative humidity, and effective cloud droplet size. To understand the complex relationship between aerosol and lightning, two different regions with different climatic and weather conditions, a humid region R1 (22°-29° N, 89°-92° E) and an arid region R2 (23°-28° N, 70°-76° E) of northern India, were chosen for the study domain. The results show that lightning activity was observed to occur more over the humid region R1, i.e., 1141 days (1/3 of total days), than over the arid region R2, i.e., 740 days (1/5 of total days). Also, over the humid region R1, the highest lightning flash density was recorded as nearly 4.6 × 10-4 flashes/km2/day observed for 18 days (1.5%); on the contrary, over the arid region R2, the maximum lightning flash density was observed to be 2.5 × 10-4 flashes/km2/day and occurred for about 22 days (2.9%). The analysis shows that a nonlinear relationship exists between aerosol and lightning with a highly associated influence of relative humidity. A very significant positive and negative co-relation that varies with relative humidity has been observed between AOD and lightning for both humid and arid regions. This shows relative humidity is the key factor in determining the increase or decrease of lightning activity. This study also shows that the larger the cloud droplet size, the higher the relative humidity and vice versa. This study emphasizes that aerosol concentration in the atmosphere influences cloud microphysics by modulating the size of cloud droplets and thereby regulating the lightning frequency. The atmospheric humidity is the driving factor in deciding the positive or negative co-relationship between aerosol and lightning. Supplementary Information: The online version contains supplementary material available at 10.1007/s00024-022-02981-6.

Prevalence of Developmental Co-ordination Disorder in School Children.

Developmental co-ordination disorder (DCD) is a hidden complex childhood disorder seen in school aged children. There are only few Indian literatures supporting the prevalence of DCD among Indian school children but this current research has attempted to make a confirmatory diagnosis of DCD. Objective of the study was to estimate the prevalence rate of DCD among school children. This study was designed as cross-sectional study; sample size was 944 students. Outcome measure used was Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM V) criteria. On screening 944 children the overall prevalence rate was 3.8% (36). The gender wise distribution showed more male children were affected compared to female children. Age wise distribution showed a higher prevalence rate between the age group 9 to 14 y. This study yielded a comprehensive, well controlled overview in the prevalence of DCD, therefore early diagnosis is now a great concern and areas of theoretical, and clinical importance should be considered.

Patient experiences and health system responsiveness among internal migrants: A nationwide study in 13 Indian cities.

OBJECTIVE: To report various components of health system responsiveness among poor internal migrants who availed the government health facilities in 13 Indian cities. MATERIALS AND METHODS: Cluster random sampling was used to select 50,806 migrant households, of which 14,263 households avail the government health facility in last six months. In addition, 5072 women, who sought antenatal care and 3946 women who had delivery in government health facility during last six months were also included. Data on different domains of health system responsiveness were collected using an interviewer-administered questionnaire, developed based on the World Health Survey of WHO. RESULTS: Of the eight domains of responsiveness, namely, autonomy, communication, confidentiality, dignity, choice, quality of basic facilities, prompt attention and access to family and community, seven domains, except the 'choice', are assessed, and they are moderate. Only about 30% of participants said that doctor discussed on treatment options (autonomy). And 50-60% of participants said positively for questions of clarity of communication. About 59% of participants acknowledged the confidentiality. Not more than 40% of participants said they were treated with dignity, and privacy is respected (dignity). The responses to quality basic amenities, prompt attention and access to family and community domains are fairly satisfactory. CONCLUSIONS: This study has implications as many urban poor, including migrants do not utilize the services of public healthcare facilities. Hence, a responsive health system is required. There should be a policy in place to train and orient healthcare workers on some of the domains of health system responsiveness.

MRI-Based Texture Analysis to Differentiate Sinonasal Squamous Cell Carcinoma from Inverted Papilloma.

BACKGROUND AND PURPOSE: Because sinonasal inverted papilloma can harbor squamous cell carcinoma, differentiating these tumors is relevant. The objectives of this study were to determine whether MR imaging-based texture analysis can accurately classify cases of noncoexistent squamous cell carcinoma and inverted papilloma and to compare this classification performance with neuroradiologists' review. MATERIALS AND METHODS: Adult patients who had inverted papilloma or squamous cell carcinoma resected were eligible (coexistent inverted papilloma and squamous cell carcinoma were excluded). Inclusion required tumor size of >1.5 cm and preoperative MR imaging with axial T1, axial T2, and axial T1 postcontrast sequences. Five well-established texture analysis algorithms were applied to an ROI from the largest tumor cross-section. For a training dataset, machine-learning algorithms were used to identify the most accurate model, and performance was also evaluated in a validation dataset. On the basis of 3 separate blinded reviews of the ROI, isolated tumor, and entire images, 2 neuroradiologists predicted tumor type in consensus. RESULTS: The inverted papilloma (n = 24) and squamous cell carcinoma (n = 22) cohorts were matched for age and sex, while squamous cell carcinoma tumor volume was larger (P = .001). The best classification model achieved similar accuracies for training (17 squamous cell carcinomas, 16 inverted papillomas) and validation (7 squamous cell carcinomas, 6 inverted papillomas) datasets of 90.9% and 84.6%, respectively (P = .537). For the combined training and validation cohorts, the machine-learning accuracy (89.1%) was better than that of the neuroradiologists' ROI review (56.5%, P = .0004) but not significantly different from the neuroradiologists' review of the tumors (73.9%, P = .060) or entire images (87.0%, P = .748). CONCLUSIONS: MR imaging-based texture analysis has the potential to differentiate squamous cell carcinoma from inverted papilloma and may, in the future, provide incremental information to the neuroradiologist.

Epilepsy in KCNH1-related syndromes.

KCNH1 mutations have been identified in patients with Zimmermann-Laband syndrome and Temple-Baraitser syndrome, as well as patients with uncharacterized syndromes with intellectual disability and overlapping features. These syndromes include dysmorphic facial features, nail hypo/aplasia, thumb and skeletal anomalies, intellectual disability, and seizures. We report the epilepsy phenotype in patients with KCNH1 mutations. Demographic data, electroclinical features, response to antiepileptic drugs, and results of significant diagnostic investigations of nine patients carrying mutations in KCNH1 were obtained from referring centres. Epilepsy was present in 7/9 patients. Both generalized and focal tonic-clonic seizures were observed. Complete seizure control was achieved with pharmacological treatment in 2/7 patients; polytherapy was required in 4/7 patients. Status epilepticus occurred in 4/7 patients. EEG showed a diffusely slow background in 7/7 patients with epilepsy, with variable epileptiform abnormalities. Cerebral folate deficiency and an increase in urinary hypoxanthine and uridine were observed in one patient. Epilepsy is a key phenotypic feature in most individuals with KCNH1-related syndromes, suggesting a direct role of KCNH1 in epileptogenesis, although the underlying mechanism is not understood.

The Impact of Middle Turbinate Concha Bullosa on the Severity of Inferior Turbinate Hypertrophy in Patients with a Deviated Nasal Septum.

BACKGROUND AND PURPOSE: Inferior turbinate hypertrophy and concha bullosa often occur opposite the direction of nasal septal deviation. The objective of this retrospective study was to determine whether a concha bullosa impacts inferior turbinate hypertrophy in patients who have nasal septal deviation. MATERIALS AND METHODS: The electronic medical record was used to identify sinus CT scans exhibiting nasal septal deviation for 100 adult subjects without and 100 subjects with unilateral middle turbinate concha bullosa. Exclusion criteria included previous sinonasal surgery, tumor, sinusitis, septal perforation, and craniofacial trauma. Nasal septal deviation was characterized in the coronal plane by distance from the midline (severity) and height from the nasal floor. Measurement differences between sides for inferior turbinate width (overall and bone), medial mucosa, and distance to the lateral nasal wall were calculated as inferior turbinate hypertrophy indicators. RESULTS: The cohorts with and without concha bullosa were similarly matched for age, sex, and nasal septal deviation severity, though nasal septal deviation height was greater in the cohort with concha bullosa than in the cohort without concha bullosa (19.1 ± 4.3 mm versus 13.5 ± 4.1 mm, P < .001). Compensatory inferior turbinate hypertrophy was significantly greater in the cohort without concha bullosa than in the cohort with it as measured by side-to-side differences in turbinate overall width, bone width, and distance to the lateral nasal wall (P < .01), but not the medial mucosa. Multiple linear regression analyses found nasal septal deviation severity and height to be significant predictors of inferior turbinate hypertrophy with positive and negative relationships, respectively (P < .001). CONCLUSIONS: Inferior turbinate hypertrophy is directly proportional to nasal septal deviation severity and inversely proportional to nasal septal deviation height. The effect of a concha bullosa on inferior turbinate hypertrophy is primarily mediated through influence on septal morphology, because the nasal septal deviation apex tends to be positioned more superior from the nasal floor in these patients.

Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome.

Zimmermann-Laband syndrome (ZLS) is a developmental disorder characterized by facial dysmorphism with gingival enlargement, intellectual disability, hypoplasia or aplasia of nails and terminal phalanges, and hypertrichosis. We report that heterozygous missense mutations in KCNH1 account for a considerable proportion of ZLS. KCNH1 encodes the voltage-gated K(+) channel Eag1 (Kv10.1). Patch-clamp recordings showed strong negative shifts in voltage-dependent activation for all but one KCNH1 channel mutant (Gly469Arg). Coexpression of Gly469Arg with wild-type KCNH1 resulted in heterotetrameric channels with reduced conductance at positive potentials but pronounced conductance at negative potentials. These data support a gain-of-function effect for all ZLS-associated KCNH1 mutants. We also identified a recurrent de novo missense change in ATP6V1B2, encoding the B2 subunit of the multimeric vacuolar H(+) ATPase, in two individuals with ZLS. Structural analysis predicts a perturbing effect of the mutation on complex assembly. Our findings demonstrate that KCNH1 mutations cause ZLS and document genetic heterogeneity for this disorder.

Immunological profiling in chronic rhinosinusitis with nasal polyps reveals distinct VEGF and GM-CSF signatures during symptomatic exacerbations.

BACKGROUND: The mechanisms and immune pathways associated with chronic rhinosinusitis (CRS) are not fully understood. Immunological changes during acute exacerbation of CRS may provide valuable clues to the pathogenesis and perpetuation of the disease. OBJECTIVE: To characterize local and systemic immune responses associated with acute worsening of sinonasal symptoms during exacerbation in CRS with nasal polyps (CRSwNP) compared to controls. METHODS: This was a non-interventional prospective study of individuals with CRSwNP and normal controls. Subjects underwent a baseline visit with collection of nasal secretions, nasal washes, and serum specimens. Within 3 days of acute worsening of sinonasal symptoms, subjects underwent a study visit, followed by a post-visit 2 weeks later. The sinonasal outcome test-22 (SNOT-22) scores and immunological parameters in the specimens were analysed using a novel, unsupervised learning method and by conventional univariate analysis. RESULTS: Both CRSwNP patients and control subjects showed a significant increase in SNOT-22 scores during acute exacerbation. Increased nasal levels of IL-6, IL-5, and eosinophil major basic protein were observed in CRSwNP patients. A network analysis of serum specimens revealed changes in a set of immunological parameters, which are distinctly associated with CRSwNP but not with controls. In particular, systemic increases in VEGF and GM-CSF levels were notable and were validated by a conventional analysis. CONCLUSIONS: CRSwNP patients demonstrate distinct immunological changes locally and systemically during acute exacerbation. Growth factors VEGF and GM-CSF may be involved in the immunopathogenesis of subjects with CRS and nasal polyps experiencing exacerbation.

Radiation dose reduction in paranasal sinus CT using model-based iterative reconstruction.

BACKGROUND AND PURPOSE: CT performed with Veo model-based iterative reconstruction has shown the potential for radiation-dose reduction. This study sought to determine whether Veo could reduce noise and improve the image quality of low-dose sinus CT. MATERIALS AND METHODS: Twenty patients consented to participate and underwent low- and standard-dose sinus CT on the same day. Standard-dose CT was created with filtered back-projection (120 kV[peak], 210 mA, 0.4-second rotation, and 0.531 pitch). For low-dose CT, mA was decreased to 20 (the remaining parameters were unchanged), and images were generated with filtered back-projection and Veo. Standard- and low-dose datasets were reconstructed by using bone and soft-tissue algorithms, while the low-dose Veo reconstruction only had a standard kernel. Two blinded neuroradiologists independently evaluated the image quality of multiple osseous and soft-tissue craniofacial structures. Image noise was measured by using multiple regions of interest. RESULTS: Eight women and 12 men (mean age, 63.3 years) participated. Volume CT dose indices were 2.9 mGy (low dose) and 31.6 mGy (standard dose), and mean dose-length products were 37.4 mGy-cm (low dose) and 406.1 mGy-cm (standard dose). Of all the imaging series, low-dose Veo demonstrated the least noise (P < .001). Compared with filtered back-projection low-dose CT using soft-tissue and bone algorithms, Veo had the best soft-tissue image quality but the poorest bone image quality (P < .001). CONCLUSIONS: Veo significantly reduces noise in low-dose sinus CT. Although this reduction improves soft-tissue evaluation, thin bone becomes less distinct.

The genetic basis of DOORS syndrome: an exome-sequencing study.

BACKGROUND: Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. We aimed to identify the genetic basis of this syndrome by sequencing most coding exons in affected individuals. METHODS: Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. Participants were recruited from 26 centres in 17 countries. Families described in this study were enrolled between Dec 1, 2010, and March 1, 2013. Collaborating physicians enrolling participants obtained clinical information and DNA samples from the affected child and both parents if possible. We did whole-exome sequencing in affected individuals as they were enrolled, until we identified a candidate gene, and Sanger sequencing to confirm mutations. We did expression studies in human fibroblasts from one individual by real-time PCR and western blot analysis, and in mouse tissues by immunohistochemistry and real-time PCR. FINDINGS: 26 families were included in the study. We did exome sequencing in the first 17 enrolled families; we screened for TBC1D24 by Sanger sequencing in subsequent families. We identified TBC1D24 mutations in 11 individuals from nine families (by exome sequencing in seven families, and Sanger sequencing in two families). 18 families had individuals with all five main features of DOORS syndrome, and TBC1D24 mutations were identified in half of these families. The seizure types in individuals with TBC1D24 mutations included generalised tonic-clonic, complex partial, focal clonic, and infantile spasms. Of the 18 individuals with DOORS syndrome from 17 families without TBC1D24 mutations, eight did not have seizures and three did not have deafness. In expression studies, some mutations abrogated TBC1D24 mRNA stability. We also detected Tbc1d24 expression in mouse phalangeal chondrocytes and calvaria, which suggests a role of TBC1D24 in skeletogenesis. INTERPRETATION: Our findings suggest that mutations in TBC1D24 seem to be an important cause of DOORS syndrome and can cause diverse phenotypes. Thus, individuals with DOORS syndrome without deafness and seizures but with the other features should still be screened for TBC1D24 mutations. More information is needed to understand the cellular roles of TBC1D24 and identify the genes responsible for DOORS phenotypes in individuals who do not have a mutation in TBC1D24. FUNDING: US National Institutes of Health, the CIHR (Canada), the NIHR (UK), the Wellcome Trust, the Henry Smith Charity, and Action Medical Research.

Evaluating the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium: a prospective, randomized, double blind, placebo-controlled study.

BACKGROUND: Patients undergoing craniotomy, experience moderate to severe pain in postoperative period. Flupirtine does not have side effects like sedation and increase postoperative bleeding, so it may be a useful analgesic in neurosurgical patients. We designed this prospective, randomized, double blind, placebo-controlled study to evaluate the role of flupirtine for postcraniotomy pain and compare it with diclofenac sodium. MATERIALS AND METHODS: A total of 390 adults (18 to 70 y), American Society of Anaesthesiologists I and II, of either sex, undergoing elective craniotomy, were randomly divided into 3 equal groups of 130 each. Group 1 (control) received placebo, group 2 (diclofenac) received tablet diclofenac 50 mg, and group 3 (flupirtine) received capsule flupirtine 100 mg. All medications were given 8 hourly on second postoperative day for 48 hours. Visual Analogue Scale score, level of sedation and incidence of side effects were observed. RESULTS: Nineteen patients were dropped from the study and therefore subsequent analysis was carried out for 371 patients only. There was significant reduction of Visual Analogue Scale score in flupirtine and diclofenac group when compared to control (P<0.0001). Pain relief observed in control, flupirtine, and diclofenac group was 69.8%, 90.2%, and 90.5%, respectively. Need of rescue analgesia was significantly less in flupirtine and diclofenac group as compared to control (P<0.0001). No significant difference was observed among the groups in regards to adverse effects. CONCLUSION: We conclude that oral flupirtine 100 mg is safe and as effective as oral diclofenac sodium 50 mg in reducing postcraniotomy pain.

Medium- and long-term outcome of laparoscopic redo fundoplication.

BACKGROUND: For a small subset of patients, laparoscopic fundoplication fails, typically resulting in recurrent reflux or severe dysphagia. Although redo fundoplications can be performed laparoscopically, few studies have examined their long-term efficacy. METHODS: Using a prospectively maintained database, the authors identified and contacted 41 patients who had undergone redo laparoscopic fundoplications at the University of Washington between 1996 and 2001. The median follow-up period was 50 months (range, 20-95 months). Current symptoms were compared with those acquired and entered into the authors' database preoperatively. Patients also were asked to return for esophageal manometry and pH testing. RESULTS: All redo fundoplications were performed laparoscopically. There were no conversions. The most common indication for redo fundoplication was recurrent reflux. The most common anatomic abnormality was a herniated wrap. Heartburn improved in 61%, regurgitation in 69%, and dysphagia in 74% of the patients. Complete resolution of these symptoms was achieved, respectively, in 45%, 41% and 38% of these same patients. Overall, 68% of the patients rated the success of the procedure as either "excellent" or "good," and 78% said they were happy they chose to have it. For those who underwent reoperation for gastroesophageal reflux disease, distal esophageal acid exposure according to 24-h pH monitoring decreased after redo fundoplication from 15.7% +/- 18.1% to 3.4% +/- 3.6% (p = 0.041). CONCLUSION: Although not as successful as primary fundoplication, a majority of patients can expect durable improvement in their symptoms with a laparoscopic redo fundoplication.

Identification of bioneutralization epitopes of human follicle stimulating hormone in the regions 31-52 and 66-75 of its beta-subunit.

The crucial role played by follicle stimulating hormone (FSH) in regulating both male and female reproduction and the possibilities of developing contraceptive methods for males by blocking the function of the hormone, makes it important to delineate the hormone-specific bioneutralization epitopes of human follicle stimulating hormone (hFSH) on its beta-subunit. Predictive methods were used to identify the potential surface-oriented regions of hFSH-beta. Peptides corresponding to these regions, i.e. 31-52, 66-75 and 86-95 hFSH-beta, were synthesized, anti-peptide antibodies were elicited in rabbits and the properties of these antisera to bind hFSH and neutralize its biological activity were assessed. Anti-31-52 hFSH-beta antisera bound hFSH specifically, whereas anti-66-75 and anti-86-95 hFSH-beta antisera did not show any detectable binding, proving the region 31-52 hFSH-beta to be a specific antigenic determinant of hFSH. The bioneutralizing abilities of the anti-peptide antibodies were assessed by measuring the hFSH-induced progesterone secretion by rat granulosa cells in vitro. Antibodies to 31-52 and 66-75 hFSH-beta neutralized the bioactivity of hFSH, but anti-86-95 hFSH-beta antibodies did not. Furthermore, the three linear peptides and two disulphide looped peptides of 31-52 hFSH-beta and 86-95 hFSH-beta were also subjected to the in-vitro granulosa cell assay. The linear peptides 31-52 hFSH-beta and 66-75 hFSH-beta and the cyclic 31-52 hFSH-beta disulphide loop peptide significantly inhibited the hFSH-induced progesterone secretion by rat granulosa cells, but the linear 86-95 hFSH-beta peptide and the corresponding cyclic disulphide loop peptide did not. The results clearly show that the regions 31-52 and 66-75 of hFSH-beta harbor bioneutralization epitopes of the hormone. The studies also indicate that cyclization of the linear 31-52 hFSH-beta peptide greatly enhances receptor recognition and that the region 66-75 hFSH-beta may also be involved in hormone-receptor interaction.