EFFECTS OF SOCIAL ESTRANGEMENT ON YOUNG PEOPLE'S MATURATION: A REVIEW OF THE RESEARCH.

A major issue among adolescents in recent years has been social isolation, or the sensation cut off and alone from peers and society. The effects of social isolation on youngsters and adolescents are investigated with special attention paying to the possible negative effects on their physical and mental health. Multiple studies have shown a link between adversity in life domains and adolescent social isolation. Firstly, it can have a major effect on mental health, raising the probability of experiencing things like anxiety, sadness and even suicidal thoughts. Second, it prevents the development of vital social abilities, making it harder to make and keep close friends. In addition, social isolation is associated with worse academic performance, which in turn reduces the number of courses a student can take and the number of jobs they can have in the future. After looking over 520 papers, 15 were chosen for the systematic review. Four researches reported the implications on general health, while two investigations reported on ramifications affecting the Hypothalamic-pituitary-adrenal (HPA) axis area along with social and mental growth of children. In conclusion, social isolation affects youth development across a wide spectrum, including psychological well-being, interpersonal skills, and academic success. Children and adolescents who experience isolation are more likely to suffer from anxiety and sadness, according to the review's findings. Cortical levels rise and mental growth slows in socially isolated children. Children and adolescents should be monitored by health professionals during and after the COVID-19 pandemic to ensure that their mental and physical health needs are met.

Outcome of percutaneous balloon kyphoplasty in vertebral compression fractures.

BACKGROUND: Incidence of vertebral compression fractures (VCFs) is increasing due to increase in human life expectancy and prevalence of osteoporosis. Vertebroplasty had been traditional treatment for pain, but it neither attempts to restore vertebral body height nor eliminates spinal deformity and is associated with a high rate of cement leakage. Balloon kyphoplasty involves introduction of inflatable balloon into the fractured body of vertebra for elevation of the end-plates prior to fixation of the fracture with bone cement. This study evaluates short term functional and radiological outcomes of balloon kyphoplasty. The secondary aim is to explore short-term complications of the procedure. MATERIALS AND METHODS: A retrospective study of 199 kyphoplasty procedures in 135 patients from March 2009 to March 2012 were evaluated with short form-36 (SF-36) score, visual analogue scale (VAS), detailed neurological and radiological evaluations. The mean followup was 18 months (range 12-20 months). Statistical analysis including paired sample t-test was done with statistical package for social sciences. RESULTS: Statistically significant improvements in SF-36 (from 34.29 to 48.53, an improvement of 14.24, standard deviation (SD) - 20.08 P < 0.0001), VAS (drop of 4.49, from 6.74 to 2.24, SD - 1.44, P < 0.0001), percentage restoration of lost vertebral height (from 30.62% to 16.19%, improvement of 14.43%, SD - 15.37, P < 0.0001) and kyphotic angle correction (from 17.41° to 10.59°, improvement of 6.82, SD - 7.26°, P < 0.0001) were noted postoperatively. Six patients had cement embolism, 65 had cement leak and three had adjacent level fracture which required repeat kyphoplasty later. One patient with history of ischemic heart disease had cardiac arrest during the procedure. No patients had neurological deterioration in the followup period. CONCLUSIONS: Kyphoplasty is a safe and effective treatment for VCFs. It improves physical function, reduces pain and corrects kyphotic deformity.

Maternal mortality in seven districts of Uttar Pradesh--an ICMR task force study.

Maternal mortality is a major health and development concern. The available information on maternal mortality in rural India is inadequate and scanty. This study presented maternal mortality data from the demographically and developmentally (including for health) poor performing state of Uttar Pradesh. A descriptive, cross-sectional survey was conducted utilizing a stratified cluster sampling design between 1989-90 in eight districts of Uttar Pradesh. Four good performing districts namely, Agra, Farrukhabad, Ghaziabad and Badaun from the western region and four poor performing districts from the eastern region namely, Gorakhpur, Basti, Varanasi and Pratapgarh were chosen. A door-to-door household interview survey was carried out in the selected villages covering a population of 11.67 lakhs in 889 villages. Maternal mortality rates during 1989 ranged between 533745 per 100,000 live births except in Ghaziabad district where the rate was as low as 101 per 100,000 live births. The rate in Eastern U.P. was higher (573 per 100,000 live births) as compared to that in Western U.P. (472 per 100,000 live births). A total of 286 maternal deaths were reported during the study period. The direct obstetric causes accounted for 55.7% of maternal deaths with haemorrhage (26.4%) being the most prevalent. Anaemia and jaundice (17.4%) were the most prevalent indirect causes of maternal deaths. Most of the maternal deaths could have been prevented if timely medical care was available.

Aflatoxin B1 contamination in wheat grain samples collected from different geographical regions of India: A multicenter study.

In a multicenter study conducted by the Indian Council of Medical Research, 1,646 samples of wheat grain collected from rural and urban areas of 10 states representing different geographical regions of India were analyzed for aflatoxin B1 (AFB1). AFB1 concentrations of > or = 5 microg kg(-1) were recorded in 40.3% of the samples, and concentrations above the Indian permissible regulatory limit of 30 microg kg(-1) were found in 16% of the samples. The proportion of samples with AFB1 concentrations above the Indian regulatory limit ranged from 1.7 to 55.8% in different states, with the minimum in Haryana and the maximum in Orissa. The variation in wheat contamination among states seems to be mainly the result of unsatisfactory storage conditions. Median AFB1 concentrations of 11, 18, and 32 microg kg(-1) were observed in samples from Uttar Pradesh, Assam, and Orissa, respectively; concentrations in other states were <5 microg kg(-1). The maximum AFB1 concentration of 606 microg kg(-1) was observed in a sample from the state of Uttar Pradesh. The calculated probable daily intakes of AFB1 through consumption of contaminated wheat for the population in some states were much higher than the suggested provisional maximum tolerable daily intake. Human health hazards associated with such AFB1 exposure over time cannot be ruled out.

Residues of DDT and HCH in wheat samples collected from different states of India and their dietary exposure: A multicentre study.

Under a multicentre study conducted by the Indian Council of Medical Research, 1712 samples of wheat grain/flour were collected from urban and rural areas in 11 states representing different geographical regions of India. These samples were analysed for residues of DDT (2,2-bis (p-chlorophenyl)-1,1,1-trichloro ethane) and different isomers of HCH (1,2,3,4,5,6-hexachloro cyclohexane, a mixture of isomers) by gas-liquid chromatography. Residues of DDT were detected in 59.4% of 1080 samples of wheat grain and in 78.2% of 632 samples of wheat flour. Different isomers of HCH were present in about 45-80% of the samples of wheat grain/flour. Medians of DDT and total HCH, respectively, for pooled samples of wheat grain were 0.013 and 0.035 mg kg(-1), while those for wheat flour were 0.01 and 0.02 mg kg(-1). Estimated daily intakes of DDT and different isomers of HCH through the consumption of wheat contaminated at their median and 90th percentiles constituted a small proportion of their acceptable daily intakes. Amongst the pesticide residues analysed, statutory maximum residue limits have been fixed only for gamma-HCH in wheat in India, as 0.1 mg kg(-1) in wheat grain and zero in wheat flour. Residue levels of gamma-HCH exceeded these maximum residue limits in five of 1080 samples of wheat grain and in 340 of 632 samples of wheat flour. The failure to meet the requirement of the gamma-HCH maximum residue limit in large number of wheat flour samples was attributed to the fixation of practically unachievable zero limit. Comparing the previous studies and the present one, the levels of residues of DDT and HCH in wheat were significantly decreased.

Aflatoxin B(1) contamination of parboiled rice samples collected from different states of India: A multi-centre study.

Under a multi-centre study conducted by the Indian Council of Medical Research, 1,511 samples of parboiled rice were collected from rural and urban areas of 11 states representing different geographical regions of India. These samples were analysed for contamination with aflatoxin B(1.) The presence of aflatoxin B(1) at levels=5 microg g(-1) was found in 38.5% of the total number of samples of the parboiled rice. About 17% of the total samples showed the presence of aflatoxin B(1) above the Indian regulatory limit of 30 microg kg(-1). No statistically significant difference in percentage of samples contaminated with >30 microg kg(-1) was observed between pooled rural (19.4%) and urban (14.5%) data. A median value of 15 microg kg(-1) of aflatoxin B(1) was observed in samples from Assam, Bihar and Tripura. In all other states surveyed the median value was <5 microg?kg(-1).

Prevalence of anemia among pregnant women and adolescent girls in 16 districts of India.

BACKGROUND: Nutritional anemia is one of India's major public health problems. The prevalence of anemia ranges from 33% to 89% among pregnant women and is more than 60% among adolescent girls. Under the anemia prevention and control program of the Government of India, iron and folic acid tablets are distributed to pregnant women, but no such program exists for adolescent girls. OBJECTIVE: To assess the status of anemia among pregnant women and adolescent girls from 16 districts of 11 states of India. METHODS: A two-stage random sampling method was used to select 30 clusters on the basis of probability proportional to size. Anemia was diagnosed by estimating the hemoglobin concentration in the blood with the use of the indirect cyanmethemoglobin method. RESULTS: The survey data showed that 84.9% of pregnant women (n = 6,923) were anemic (hemoglobin < 110 g/L); 13.1% had severe anemia (hemoglobin < 70 g/L), and 60.1% had moderate anemia (hemoglobin > or = 70 to 100 g/L). Among adolescent girls (n = 4,337)from 16 districts, the overall prevalence of anemia (defined as hemoglobin < 120 g/L) was 90.1%, with 7.1% having severe anemia (hemoglobin < 70 g/L). CONCLUSIONS: Any intervention strategy for this population must address not only the problem of iron deficiency, but also deficiencies of other micronutrients, such as B12 and folic acid and other possible causal factors.

Efficacy of nonhormonal vaginal contraceptives from a hydrogel delivery system.

This investigation describes the synthesis of a biodegradable hydrogel composed of a core surrounded by four concentric sheaths containing dextran, copolymers of polylactide and epsilon-caprolactone. The hydrogel was impregnated with iron (II) d-gluconate dihydrate, which causes complete spermiostasis due to lipid peroxidation, ascorbic acid to increase the viscosity of the cervical mucus and mixtures of polyamino and polycarboxylic acids to sustain vaginal pH close to 4.5. The combined effects of the agents in the daily eluates of the hydrogel were efficacious up to 16 days, within 30 s, as shown by sperm penetration tests. For in vivo studies, rabbits were chosen as the experimental model because they are easy to handle and the female is always in estrus. The anterior vagina of estrous female rabbits was instilled with the hydrogel, and then inseminated with the semen from a fertile male. Postinsemination flush from the female rabbits showed that all of the sperm were dead. These observations demonstrate the potential for the development of a biocompatible, nonhormonal, intravaginal contraceptive device.

Iodine deficiency disorders in 15 districts of India.

METHODS: A multicentre study to assess iodine deficiency disorders (goitre and deaf-mutism/cretinism) in 1, 45, 264 children (6 - <12 years old) from 15 districts of ten states was carried out during 1997-2000. Urinary iodine excretion was also determined in 27481 children, while iodine content was estimated in 5881 samples of edible salt. The sampling methodology followed was a "30 cluster survey". RESULTS: The overall prevalence of goitre was 4.78% (4.66% of grade I and 0.12% of grade II) amongst the children examined. The highest prevalence of 31.02% goitre was observed in Dehradun district, while the lowest prevalence of 0.02% goitre was recorded in Bishnupur and Badaun districts. The overall prevalence of cretinism among children examined from seven districts was 0.072% whereas that of deaf-mutism was 0.27% among children examined from 8 districts. Median urinary iodine values was marginally less than the WHO cut-off values only in children of the 3 out of the 15 districts surveyed. Iodine content was found to be adequate in 55.45% of the salt samples. CONCLUSION: The results suggested a significant decline in the prevalence of goitre in most parts of the country.

Residues of DDT and HCH pesticides in rice samples from different geographical regions of India: a multicentre study.

As part of a multicentre study conducted by the Indian Council of Medical Research, 2000 samples of rice were collected from rural and urban areas of 13 states representing different geographical regions of India. The samples were analyzed for residues of DDT [2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and different isomers of HCH [1,2,3,4,5,6-hexachlorocyclohexane, a mixture of isomers] by gas-chromatography. Residues of DDT and HCH, respectively, were detected in about 58 and 73% of the samples analysed. Medians of both DDT and HCH in rice samples were around 0.01 mg kg (-1). Concentrations of alpha-, beta-, gamma- and delta-HCH exceeded a maximum residue limit of 0.05 mg kg (-1) for each isomer in rice fixed by the Ministry of Health and Family Welfare of the Indian Government in 4.3, 2.6, 1.7 and 1.2% of the samples, respectively. There is no statutory limit fixed in India for DDT residues in cereals. Its maximum residue limit of 0.1 mg kg (-1) in cereals recommended by Codex was exceeded by about 2% of the samples examined. Estimated intake of DDT and isomers of HCH through consumption of rice contaminated at their median and 90th percentiles constituted a small proportion of their acceptable daily intakes.

Resuscitation of asphyxiated newborns with room air or 100% oxygen at birth: a multicentric clinical trial.

OBJECTIVE: To compare the short-term efficacy of room air versus 100% oxygen for resuscitation of asphyxic newborns at birth. DESIGN: Multicentric quasi randomized controlled trial. SETTING: Teaching hospitals. INCLUSION CRITERIA: Asphyxiated babies weighing greater than 1000 grams, with heart rate less than 100 per min and/or apnea, unresponsive to nasopharyngeal suction and tactile stimuli and having no lethal abnormalities. INTERVENTION: Asphyxiated neonates born on odd dates were given oxygen and those on even dates room air for resuscitation. OUTCOME MEASURES: Primary: Apgar score at 5 minutes; Secondary: Mortality and Hypoxic ischaemic encephalopathy (HIE) during first 7 days of life. RESULTS: A total of 431 asphyxiated babies, 210 in the room air and 221 in 100% oxygen group were enrolled for the study. Both the groups were comparable for maternal, intrapartum and neonatal characteristics. The heart rates in room air and 100% oxygen groups were comparable at 1 minute (94 bpm and 88 bpm), 5 minutes (131 bpm and 131 bpm) and 10 minutes (135 bpm and 136 bpm). Median apgar scores at 5 min [7 versus 7] and 10 minutes [8 versus 8 ], in the room air and oxygen groups respectively, were found to be comparable. Median time to first breath (1.5 versus 1.5 minutes) was similar in the room air and oxygen group. Median time to first cry (2.0 versus 3.0 minutes) and median duration of resuscitation (2.0 versus 3 minutes) were significantly shorter in the room air group. The number of babies with HIE during first seven days of life in the two treatment groups (35.7% babies in room air and 37.1% in the 100% oxygen group) were similar. There was also no statistically significant difference in the overall and asphyxia related mortality in the two treatment groups (12.4% and 10.0% in room air versus 18.1% and 13.6% in oxygen group). CONCLUSION: Room air appears as good as 100% oxygen for resuscitation of asphyxic newborn babies at birth.

Vitamin A deficiency disorders in 16 districts of India.

A multicentre study to assess vitamin A deficiency disorders (Bitot's spot and corneal scars) in 164,512 children (< 6 years) and night blindness among 113,202 children (24-71 months) from 16 districts of 11 states was carried out during 1997-2000. The prevalence of night blindness among 6,633 pregnant women from 15 districts was also assessed. The sampling methodology followed was a "30 cluster survey". The highest prevalence of Bitot's spot (4.71%), corneal scar (0.5%) and night blindness (5.17%) in children was found in Gaya district whereas the highest prevalence of night blindness (19.62%) among pregnant women was observed in Dibrugarh. No case of Bitot's spot was found in children screened from Mandi, Dehradun and Badaun districts. Similarly prevalance of night blindness was 'nil' among pregnant women of Badaun, Baramulla, Dehradun, Mainpuri, Srinagar, Bikaner and Raigarh.

Modulation of ovarian function in female dogs immunized with bovine luteinizing hormone receptor.

Adult female dogs were immunized with 0.5 mg bovine luteinizing hormone receptor (LH-R) encapsulated in a silastic subdermal implant and subsequently with four intramuscular booster injections of 0.1 mg LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks post-implant. The appearance of LH-R antibody was associated with a decline in the serum progesterone concentrations to a range of 0-0.5 ng/ml until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation and corpus luteum function in immunized dogs. The immunized dogs did not show signs of 'standing heat' and failed to ovulate when induced by LH-RH challenge. Serum oestradiol levels, however, remained in the range of 30-40 pg/ml in both the immunized and the control dogs. With the decline in the antibody titres, the hormonal profile and vaginal cytology returned to a fertile state and the dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs immunized with LH-R did not show any serious metabolic, local or systemic adverse effects. The hypothalamic--pituitary gonadal axis remained intact as indicated by little difference in pituitary LH levels between control and immunized animals, and by the release of LH by LH-RH challenge. These studies demonstrate that active immunization of female dogs with LH-R could immunomodulate ovarian function to cause a reversible state of infertility. It may be postulated that, due to extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other vertebrates.

Low-amplitude, extremely low frequency magnetic fields for the treatment of osteoarthritic knees: a double-blind clinical study.

CONTEXT: Noninvasive magnetotherapeutic approaches to bone healing have been successful in past clinical studies. OBJECTIVE: To determine the effectiveness of low-amplitude, extremely low frequency magnetic fields on patients with knee pain due to osteoarthritis. DESIGN: Placebo-controlled, randomized, double-blind clinical study. SETTING: 4 outpatient clinics. PARTICIPANTS: 176 patients were randomly assigned to 1 of 2 groups, the placebo group (magnet off) or the active group (magnet on). INTERVENTION: 6-minute exposure to each magnetic field signal using 8 exposure sessions for each treatment session, the number of treatment sessions totaling 8 during a 2-week period, yielded patients being exposed to uniform magnetic fields for 48 minutes per treatment session 8 times in 2 weeks. The magnetic fields used in this study were generated by a Jacobson Resonator, which consists of two 18-inch diameter (46-cm diameter) coils connected in series, in turn connected to a function generator via an attenuator to obtain the specific amplitude and frequency. The range of magnetic field amplitudes used was from 2.74 x 10(-7) to 3.4 x 10(-8) G, with corresponding frequencies of 7.7 to 0.976 Hz. OUTCOME MEASURES: Each subject rated his or her pain level from 1 (minimal) to 10 (maximal) before and after each treatment and 2 weeks after treatment. Subjects also recorded their pain intensity in a diary while outside the treatment environment for 2 weeks after the last treatment session (session 8) twice daily: upon awakening (within 15 minutes) and upon retiring (just before going to bed at night). RESULTS: Reduction in pain after a treatment session was significantly (P < .001) greater in the magnet-on group (46%) compared to the magnet-off group (8%). CONCLUSION: Low-amplitude, extremely low frequency magnetic fields are safe and effective for treating patients with chronic knee pain due to osteoarthritis.

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.

A Canadian multicenter, double-blind study of paroxetine and fluoxetine in major depressive disorder.

BACKGROUND: Recent studies have suggested clinical differences among selective serotonin reuptake inhibitors. In a 12-week randomized, multicenter, double-blind trial, the antidepressant and anxiolytic efficacy of the selective serotonin reuptake inhibitors paroxetine and fluoxetine was compared in patients with moderate to severe depression. METHODS: A total of 203 patients were randomized to fixed doses (20 mg/day) of paroxetine or fluoxetine for the first six weeks of therapy. From week 7-12, dosing could be adjusted biweekly, as required (paroxetine 20-50 mg/day, and fluoxetine 20-80 mg/day). The mean prescribed doses were paroxetine 25.5 mg/day (range 20.0-40.2 mg/day), and fluoxetine 27.5 mg/day (range 20.0-59.5 mg/day). Emergence of motor nervousness or restlessness was assessed using the ESRS scale for akathisia. RESULTS: Both active treatments demonstrated comparable antidepressant efficacy (HAM-D, CGI). Anxiolytic activity of the two drugs (COVI, STAI, HAM-D) was also comparable. However, paroxetine was found to be superior to fluoxetine on two subscore measures at week 1 of therapy (HAM-D Agitation item, p < 0.05; Psychic Anxiety item, p < 0.05), with no differences detected after week 2. The overall incidence of adverse effects was comparable in the two treatment groups. Constipation, dyspepsia, tremor, sweating and abnormal ejaculation were more common in paroxetine-treated subjects, whereas nausea and nervousness were more frequent in fluoxetine-treated patients. Weight loss was more common in the fluoxetine versus paroxetine group (11.88% versus 2.94%, respectively). ESRS scores for akathisia were low throughout the study and showed little change. LIMITATIONS: Differences observed between the two drugs in antianxiety effects were limited to two measures of anxiety among several others. DISCUSSION: The data indicate that paroxetine and fluoxetine have comparable antidepressant and anxiolytic efficacy. Paroxetine appears to produce an earlier improvement in agitation and psychic anxiety symptoms compared with fluoxetine.

The treatment of negative symptoms: a clinical and methodological study.

The primary objective of this study was to evaluate the efficacy, safety and tolerability of remoxipride (controlled release) versus haloperidol in patients with negative symptoms. The study comprised a multicentre, randomised, double-blind, parallel-group clinical trial. Two hundred and five patients were randomised to either remoxipride or haloperidol. Patients eligible for this study were aged 18-65 years, met the DSM-III-R diagnosis for chronic schizophrenia and the Positive and Negative Symptoms Scale (PANSS) criteria for predominant negative symptoms. There was a statistically significant reduction in the PANSS scores of at least 20% from baseline to last rating for 39 remoxipride (49.4%) and 45 haloperidol (47.6%) treated patients. There were no statistical differences found between the two treatment groups with respect to improvement of negative symptoms and adverse events. The PANSS data suggest that both remoxipride and haloperidol improve the cluster of negative symptoms concerned with social functioning. In addition, the design of the study provides a methodology that is appropriate to the study of primary negative symptoms in schizophrenia.

DDT and HCH residues in dairy milk samples collected from different geographical regions of India: a multicentre study.

Under a multicentre study conducted by the Indian Council of Medical Research, 2205 samples of dairy milk were collected from rural and urban areas of 12 states representing different geographical regions of India. These samples were analysed for residues of DDT and different isomers of HCH by gas-liquid chromatography. Analytical quality assurance between various participating laboratories was ensured through analysis of check samples. The residues of DDT and HCH were detected in more than 80% of samples analysed. Concentrations of DDT residues, alpha-HCH, beta-HCH, gamma-HCH and delta-HCH exceeded their maximum residue limits prescribed by the Ministry of Health and Family Welfare of the Indian Government in 37, 21, 42, 28 and 4% of the samples, respectively. Median values of DDT and HCH found in dairy milk in India were more than the corresponding values reported from most other countries. The results showed significant variations in the incidence as well as level of these contaminants in dairy milk from different regions of the country.

A Canadian multicenter study of three fixed doses of controlled-release ipsapirone in outpatients with moderate to severe major depression.

Ipsapirone, an azapirone with 5-hydroxytryptamine (5-HT1A) partial agonist activity, has been shown in preliminary studies to be effective in the treatment of major depressive disorder. This 8-week, randomized, double-blind study compared the efficacy, safety, and tolerability of three fixed doses of controlled-release ipsapirone (10-, 30-, and 50-mg dose once daily) with placebo in 410 patients with moderate to severe major depression (Hamilton Rating Scale for Depression [HAM-D] score > or = 20). The 10-mg ipsapirone treatment arm was discontinued early in the study. A total of 390 patients were eligible for evaluation in the intent-to-treat sample. The primary efficacy variable was the change in HAM-D total score from baseline to visit 8. There was no significant difference in efficacy in the two treatment groups versus the placebo group. The overall treatment response, defined as a 50% decrease in the HAM-D total score from baseline, was 43% with ipsapirone 50 mg given once daily, 34% with ipsapirone 30 mg given once daily, and 35% with placebo. In subanalyses, ipsapirone 50 mg given once daily was superior to placebo according to the HAM-D Core Depression (mood, guilt, interest, psychomotor activity) subtotal (p = 0.0453) and Melancholic item (p = 0.0225). Ipsapirone 30 mg given once daily was superior to placebo only in patients with moderate depression (baseline HAM-D total score < or = 25; p = 0.0100). The most common adverse effect in all groups was headache. The only dose-dependent adverse effects were dizziness and nausea.

A mutation in the first transmembrane domain of the lutropin receptor causes male precocious puberty.

We describe a patient with onset of puberty at the age of 5 yr. characterized by accelerated growth, enlargement of genitalia, pubarche, and serum hormone levels compatible with noncentral precocious puberty. Exon 11 of the LH receptor gene was amplified from genomic DNA by PCR and directly sequenced. We identified a heterozygous C to T base change at nucleotide position 1126, exchanging codon 373 from Ala to Val in the first transmembrane domain. The LH receptor sequence of the parents was normal. The mutated receptor displayed an up to 7.5-fold increase in basal cAMP production compared to that of the wild-type receptor in transiently transfected COS-7 cells. Treatment of the patient with ketoconazole resulted in inconsistent suppression of serum testosterone levels. At the age of 9.1 yr, central activation of the hypothalamic-pituitary-gonadal axis occurred. Additional treatment with a GnRH agonist led to complete suppression of testosterone secretion. This is the first description of constitutive activation of the LH receptor in the first transmembrane segment. It suggests the involvement of the first transmembrane helix in signal transduction and provides further insight into the structural organization of the seven transmembrane domains of the glycoprotein hormone receptor proteins.