Severe child abuse: a study of cases reported to the police.

AIM: To investigate the characteristics of severe abuse of children and possible differences in comparison with less severe abuse. METHOD: Cases of abuse reported to the police within a single police district (n=142) in Sweden were studied. The severe cases were compared to all the remaining cases. RESULTS: Severe abuse constituted 14% of the total cases and was reported by agencies to a greater degree than minor cases. The suspected perpetrators were socially disadvantaged people in both groups. Half of the most serious cases led to conviction in the courts, compared to 8% in the reference group. The children who had been subjected to abuse were often already known to social services and reports of child abuse had frequently been made. CONCLUSION: In comparison between cases of severe and minor child abuse reported to the police, the results did not show any crucial differences except the pattern of reporting and a higher occurrence of prosecution/conviction in the severe cases. This finding places a responsibility on agencies outside of the justice system to consider all cases of reported abuse as serious warning signals and to make independent evaluations to identify risks and the possible need for child protection.

Physical child abuse in Sweden: a study of police reports between 1986 and 1996.

BACKGROUND: This study aims at investigating physical child abuse in Sweden during 1986-1996, a period when alarm was being raised about an increased number of police reports on physical child abuse. The study focuses on abuse committed by a parent or carer and aims at analyzing the victim and the perpetrator, family environment, injuries and judicial consequences of physical abuse. METHOD: All police reports on physical child abuse (0-14 years old) in a designated police district in Sweden during 1986-1996 were examined, as well as any judicial proceedings that followed. RESULTS: Our research yielded three major findings. Firstly, a large part of the increased number of police reports had to do with violence outside the family: 145 children (0.5 per 1000 children) were found abused within the families, by a parent or a carer. Secondly, there was a tendency toward males abusing boys and females abusing girls, and the biological father was the most frequent suspected perpetrator. Thirdly, 20% of the police reports led to prosecutions, and the investigations were time consuming. Known risk factors for physical abuse, such as unemployment, violent spouse relations, substance and drug abuse and poor mental health were found in several families, often among the prosecuted perpetrators. When examining incidence of physical abuse, Sweden was comparable to the other Scandinavian countries, where legislation and social context are similar. CONCLUSIONS: The numbers of physically abused children that have been reported to the police in Sweden has increased during the investigated period. Familiar risk factors are present in our study, accompanied by new findings, such as, for instance, a gender preference towards the abuse victim.

Replication of continuous-relief diffractive optical elements by conventional compact disc injection-molding techniques.

Continuous-relief diffractive optical elements have been replicated by use of conventional compact disc injection-molding techniques. Two continuous-relief microstructures, a blazed grating and a fan-out element, were chosen to evaluate the replication process. Original elements were fabricated by direct-write electron-beam lithography. Optical measurements and atomic force microscopy were used for investigating the replication fidelity.

Isolation and characterization of the human chorionic gonadotropin beta subunit (CG beta) gene cluster: regulation of transcriptionally active CG beta gene by cyclic AMP.

The alpha and beta subunit genes encoding chorionic gonadotropin (CG) are regulated transcriptionally in placental cells by cyclic AMP (cAMP). The regulatory response sequences of the alpha gene have been studied extensively. Similar studies of the CG beta subunit (CG beta) gene have not been possible because transcriptionally active sequences have not been identified in the clones isolated to date. The CG beta subunit genes form a complex cluster of seven structurally similar genes that include six CG beta-like genes and a single luteinizing hormone beta subunit (LH beta) gene. We isolated overlapping clones containing the entire CG beta/LH beta gene cluster (68 kilobases) from a human genomic cosmid library. The organization of the gene cluster was similar to that found in previous analyses, as determined by Southern blots of genomic DNA, but differed from some of the gene assignments, as determined by fragments cloned in lambda phage. The 5'-flanking sequence of the most active CG beta gene (CG beta 5) was linked to the chloramphenicol acetyltransferase (CAT) coding sequence for analyses of transient expression in different cell types. CG beta CAT was expressed preferentially in JEG-3 choriocarcinoma cells, and expression was markedly stimulated by treatment with 8-bromo-cAMP. Deletion mutagenesis of the CG beta 5'-flanking sequence revealed that multiple regions were required for maximal expression. The kinetics for cAMP stimulation of alpha CAT and CG beta CAT expression were different, suggesting that different pathways may be involved in cAMP-stimulated expression of the alpha and CG beta genes.

Human follicle-stimulating hormone beta-subunit gene encodes multiple messenger ribonucleic acids.

FSH is a pituitary gonadotropin that is encoded by separate alpha- and beta-subunit genes. We isolated a 12 kilobase (kb) DNA fragment containing the entire human FSH beta gene from a lambda phage genomic DNA library. The nucleotide sequence of the FSH beta gene predicts a 19 amino acid signal sequence and a 111 amino acid apoprotein that differs from the reported protein sequence at three residues and lacks the carboxyterminal eight amino acids, thereby bringing the human FSH beta sequence into register with those described for other mammalian species. Southern blot analyses of human genomic DNA are consistent with a single copy of the FSH beta gene per haploid genome. The FSH beta transcriptional unit spans 3.9 kb and contains two introns. The second intron (1.4 kb) is located between amino acids 35 and 36, a position that is strictly conserved among all of the glycoprotein hormone beta-subunit genes. The first intron occurs 6 base pairs upstream from the start of translation in a location analogous to that of the TSH beta gene. The first exon contains an alternate splicing donor site resulting in 5'-untranslated sequences of 63 (Exon IA) and 33 (Exon IB) bases in length. Approximately 65% of transcripts contain exon IA and 35% contain exon IB. Two different polyadenylation sites are also used. One polyadenylation site coincides with the stop codon, while the other site, which is used in greater than 80% of FSH beta mRNA transcripts, is located approximately 1 kb downstream, resulting in an unusually long 3'-untranslated sequence. The distribution of polyadenylation sites is similar for FSH beta mRNAs containing either Exons IA or IB suggesting that intron processing and polyadenylation are regulated independently. Thus, at least four distinct species of FSH beta mRNA transcripts, all encoding identical peptides, are processed from a single FSH beta gene. The distribution of different FSH beta mRNAs is similar in normal human pituitary tissue and several different FSH producing pituitary adenomas.

Glycoprotein hormone genes are expressed in clinically nonfunctioning pituitary adenomas.

Approximately 25% of patients with pituitary adenomas have no clinical or biochemical evidence for excess hormone secretion and are classified as having null cell or nonfunctioning adenomas. To characterize the cell type of these tumors, we analyzed pituitary hormone gene expression in clinically nonfunctioning pituitary adenomas using specific oligonucleotide probes for the messenger (m)RNAs encoding growth hormone, prolactin, ACTH, and the glycoprotein hormone subunits, alpha, luteinizing hormone (LH)beta, follicle-stimulating hormone (FSH)beta, and thyroid-stimulating hormone (TSH)beta. Expression of one or more of the anterior pituitary hormone genes was found in 12/14 (86%) of the patients with clinically classified nonfunctioning adenomas. Expression of one or more of the glycoprotein hormone genes (alpha, LH beta, FSH beta, TSH beta) was identified most commonly (79%) with expression of multiple beta-subunit genes in many cases. Expression of alpha-subunit mRNA was found in each of the adenomas from patients expressing one of the beta-subunit mRNAs and in three patients with no detectable beta-subunit mRNA. Although FSH beta and LH beta mRNAs were found with similar frequencies in nonfunctioning adenomas, expression of FSH beta mRNA was generally much more abundant. TSH beta mRNA was detected in only one adenoma. The levels of glycoprotein hormone subunit mRNAs were variable in different adenomas, but the lengths of the mRNAs and transcriptional start sites for the alpha- and beta-subunit genes were the same in the pituitary adenomas and in normal pituitary. Growth hormone and prolactin gene expression were not observed in the nonfunctioning adenomas, but ACTH mRNA was found in a single case. Immunohistochemistry of the adenomas confirmed production of one or more pituitary hormones in 13/14 (93%) nonfunctioning tumors, with a distribution of hormone production similar to that of the hormone mRNAs. These data indicate that pituitary adenomas originating from cells producing glycoprotein hormones are common, but are difficult to recognize clinically because of the absence of characteristic endocrine syndromes and defective hormone biosynthesis and secretion.

Gonadotropin and thyrotropin alpha- and beta-subunit gene expression in normal and neoplastic tissues characterized using specific messenger ribonucleic acid hybridization probes.

The glycoprotein hormones consist of a common alpha-subunit and distinct, but structurally related, beta-subunits which confer biological specificity. To study glycoprotein hormone gene expression, we prepared specific oligonucleotides complementary to nonhomologous regions of the alpha-subunit and each of the beta-subunit mRNAs encoding human LH, CG, TSH, and FSH. beta-Subunit mRNAs were expressed at relatively low levels in normal pituitary tissue, but were found in greater amounts in pituitary gonadotroph and thyrotroph adenomas. The lengths of the glycoprotein hormone alpha- and beta-subunit mRNAs in normal and neoplastic pituitary tissue were indistinguishable. Expression of different members of the closely related LH beta/CG beta gene family were examined in normal and neoplastic pituitary and placenta using short oligonucleotides complementary to nonhomologous regions of the genes. Although CG beta mRNA was found previously in a pituitary adenoma, none was detected in normal pituitary tissue. In placenta, there was abundant expression of the CG beta gene, but no expression of the LH beta gene, consistent with the acquisition of tissue-specific regulatory sequences in the recently evolved upstream promoter recognition site of the CG beta gene. Primer extension analysis of CG beta mRNA indicated that the same CG beta gene promoter site was used in both normal placenta and JEG-3 choriocarcinoma cells. Of the two CG beta genes that have been reported to be functional, CG beta gene 5 was preferentially expressed in both normal placenta and the neoplastic JEG-3 cell line. CG beta gene 3 expression accounted for only about 5% of the total CG beta mRNA. The previously uncharacterized human TSH beta and FSH beta mRNAs were studied in normal and neoplastic pituitary tissue. At least two species of FSH beta mRNA were found on Northern blots. Oligonucleotide-primed extension of pituitary mRNA demonstrated that FSH beta mRNA heterogeneity resulted from transcription from distinct promoter sites, encoding 5'-untranslated tracts of 48 and 83 bases. These studies demonstrate that specific oligonucleotide probes distinguish expression of the structurally related glycoprotein hormone beta-subunit mRNAs, allowing analyses of tissue-specific gene expression under different physiological conditions as well as in normal and neoplastic tissues.

Evolution of different transcriptional start sites in the human luteinizing hormone and chorionic gonadotropin beta-subunit genes.

To investigate the mechanisms related to the tissue-specific expression of luteinizing hormone (LH) in the pituitary and chorionic gonadotropin (CG) in the placenta, we compared the transcriptional start sites of the common alpha-subunit and structurally related beta-subunit genes encoding human LH and CG. The transcriptional start site of the alpha-subunit gene expressed in human pituitary and placenta is identical, encoding a mRNA with a 5'-untranslated tract of 100 bases. In contrast, the lengths of the 5'-untranslated tracts for human LH beta and CG beta mRNA are different. The human LH beta gene, like the LH beta gene in rat and cattle, transcribes a mRNA with a short 5' untranslated tract of 9 bases. Although the human CG beta gene has a TATAAA box sequence in the same location as the LH beta gene, it is not used for initiation of transcription. Instead, the promoter for the CG beta gene is located at an upstream site resulting in an extended 5' untranslated tract for CG beta mRNA of 366 bases. These results indicate that recognition of the upstream promoter site in the CG beta gene is tissue specific rather than species specific and suggest that the LH beta and CG beta genes evolved distinct regulatory regions which respond differently to intracellular signals in the pituitary and placenta.

Expression of chorionic gonadotropin-beta-like messenger ribonucleic acid in an alpha-subunit-secreting pituitary adenoma.

The mRNA and protein products produced by an alpha-subunit-secreting pituitary tumor were studied to further characterize the early steps in glycoprotein hormone biosynthesis. alpha-Subunit mRNA was readily detected by RNA blot hybridization to alpha-subunit cDNA and was qualitatively normal, with a length of about 800 bases. Although only excess free alpha-subunit was secreted by the tumor, abundant beta-subunit mRNA hybridized to a cDNA which recognized both LH beta and CG beta sequences. Surprisingly, the beta-subunit mRNA in the pituitary tumor was characteristic of CG beta mRNA. The beta-subunit mRNA migrated in parallel with placental CG beta mRNA (approximately 1000 bases) and was easily resolved from LH beta mRNA (approximately 700 bases). Using site-specific hybridization and oligonucleotide-primed extension, the beta-subunit mRNA in pituitary tumor was found to have an extended 5'-untranslated tract (366 bases) characteristic of CG beta gene transcripts rather than LH beta gene transcripts, in which the 5'-untranslated tract is only 9 bases. Activation of the CG beta-like promoter rather than the LH beta promoter indicates that the cellular mechanisms regulating tissue-specific expression of the beta-subunit gene were altered by the neoplastic changes in the pituitary tumor. Protein analysis of tumor homogenate demonstrated large amounts of alpha-subunit in the form of intact FSH and small amounts of intact LH and free alpha-subunit. Despite the presence of abundant CG beta-like mRNA in the tumor, intact hCG or hCG beta was not detected. The uncoupling of beta-subunit gene expression and protein biosynthesis in the setting of ongoing alpha-subunit biosynthesis provides a potential mechanism for unbalanced synthesis and secretion of free alpha-subunit.

Piroxicam in the treatment of primary dysmenorrhea.

In double-blind, crossover studies, piroxicam was compared with naproxen sodium and with placebo. The different parameters studied were pain intensity, patient's opinion of the drugs tested, complementary pharmacological treatment, ability to work, overall effect, treatment preference, and side effects. It was concluded that piroxicam was comparable to naproxen sodium and that piroxicam was significantly better than placebo, as regards these parameters. It was also concluded that piroxicam has an effect equivalent to that of naproxen sodium, an accepted treatment for dysmenorrhea.