[Doubtful nosological validity of the chronic whiplash syndrome]. / Fragliche nosologische Validität des chronischen Halswirbelschleudertraumasyndroms.

BACKGROUND: Since the 1980s, victims of traffic accidents in western countries increasingly report chronic symptoms which they attribute to a whiplash injury of the cervical spine. In an extensive review article published in 1996, it was, however, concluded that this so-called chronic whiplash syndrome has little nosological validity. It was now investigated whether this conclusion could be upheld by the results of later published studies. METHODS: Extensive evaluation was carried out of all the whiplash literature listed in Pubmed since 1996 with the question whether research over the last 15 years has achieved a better validation of this syndrome. RESULTS: Of the over 1,600 publications about whiplash since 1996, no study could be identified which confirmed the nosological validity of the chronic whiplash syndrome. CONCLUSION: As a positive consequence of the results of this study, accident victims suffering whiplash can be informed about the very good prognosis after whiplash in a more trustworthy way. Many iatrogenic injuries can thus be avoided. The expert opinion after whiplash without radiologically documented and/or neurologically confirmed significant acute traumatic injury which can cause chronic symptoms, should generally not be in favor of insurance benefits. The authors propose that all of a set of minimal criteria should be fulfilled if in exceptional cases a probable relationship between the trauma and chronic symptoms can be assumed.

Postmortem proteomic analysis in human amygdala of drug addicts: possible impact of tubulin on drug-abusing behavior.

Besides the ventral tegmental area and the nucleus accumbens as the most investigated brain reward structures, several reports about the relation between volume and activity of the amygdala and drug-seeking behavior have emphasized the central role of the amygdala in the etiology of addiction. Considering its proposed important role and the limited number of human protein expression studies with amygdala in drug addiction, we performed a human postmortem proteomic analysis of amygdala tissue obtained from 8 opiate addicts and 7 control individuals. Results were validated by Western blot in an independent postmortem replication sample from 12 opiate addicts compared to 12 controls and 12 suicide victims, as a second "control sample". Applying 2D-electrophoresis and MALDI-TOF-MS analysis, we detected alterations of beta-tubulin expression and decreased levels of the heat-shock protein HSP60 in drug addicts. Western blot analysis in the additional sample demonstrated significantly increased alpha- and beta-tubulin concentrations in the amygdala of drug abusers versus controls (P = 0.021, 0.029) and to suicide victims (P = 0.006, 0.002). Our results suggest that cytoskeletal alterations in the amygdala determined by tubulin seem to be involved in the pathophysiology of drug addiction, probably via a relation to neurotransmission and cellular signaling. Moreover, the loss of neuroprotection against stressors by chaperons as HSP60 might also contribute to structural alteration in the brain of drug addicts. Although further studies have to confirm our results, this might be a possible pathway that may increase our understanding of drug addiction.

[Death in seclusion - a worldwide phenomenon illustrated on fringe groups in Munich]. / Der Einsame Tod - Sterben in Randgruppen in München.

100 randomised cases where a person lived and died in isolation in Munich were analysed. Factors such as social background, living situation, education, physiological and psychological state of health were evaluated. Personal isolation (=seclusion) seems to depend on various social, financial, psychological or physical reasons. Lack of contact with other people not only leads to psychological problems, but isolation also contributes to increased illness and early death. In order to improve the present social situation in Munich preventive social measures are necessary to achieve increase in health status for the elder and a decrease in mortality rate.

Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport.

Expression of angiogenic factors such as VEGF under conditions of hypoxia or other kinds of cell stress contributes to neovascularization during wound healing. The inducible endoplasmic reticulum chaperone oxygen-regulated protein 150 (ORP150) is expressed in human wounds along with VEGF. Colocalization of these two molecules was observed in macrophages in the neovasculature, suggesting a role of ORP150 in the promotion of angiogenesis. Local administration of ORP150 sense adenovirus to wounds of diabetic mice, a treatment that efficiently targeted this gene product to the macrophages of wound beds, increased VEGF antigen in wounds and accelerated repair and neovascularization. In cultured human macrophages, inhibition of ORP150 expression caused retention of VEGF antigen within the endoplasmic reticulum (ER), while overexpression of ORP150 promoted the secretion of VEGF into hypoxic culture supernatants. Taken together, these data suggest an important role for ORP150 in the setting of impaired wound repair and identify a key, inducible chaperone-like molecule in the ER. This novel facet of the angiogenic response may be amenable to therapeutic manipulation.

A new technique for the transcrestal sinus floor elevation and alveolar ridge augmentation with press-fit bone cylinders: a technical note.

BACKGROUND: The minimally invasive sinus floor elevation as first described by Summers is limited in the volume of augmentation that is possible. In contrast, the more invasive approach is the sinuslift of Tatum which is indicated for greater bone deficiencies. Therefore, a new technique was developed for transcrestal elevation of the sinus floor and alveolar ridge augmentation with bone dowels in press-fit technique. MATERIALS & METHODS: The crestal cortical bone is cut with a hollow grinder followed by an indirect sinus floor elevation with a plunger. The cylindrical defect is then filled with a cylindrical bone transplant with the press-fit technique. RESULTS: The method was tested in ten fresh porcine skulls and was successful when applied subsequently in two fresh human cadavers (both female, age 60 and 92 years). This was followed by the insertion of another cylinder in overlapping mosaic manner with the dowel-lift technique in the left maxilla in one cadaver. A sinoscopy of the second cadaver experiment showed no perforation of the maxillary sinus membrane. The result was convincing. CONCLUSION: A new method for transcrestal elevation of the maxillary sinus floor and alveolar ridge augmentation with bone cylinders in press-fit technique was developed. The operation combines the minimally invasive approach of Summers with a large augmentation volume otherwise requiring the direct technique of Tatum. These results should encourage further preclinical experiments.

[Autopsy]. / Die wichtigsten Regeln für die Leichenschau.

The basic tasks of a physician when performing an autopsy are the establishment of death, the time of death, the manner of death and the cause of death as well as detecting communicable diseases. The person performing the autopsy must decide if a postmortem investigation is to be undertaken or whether the deceased can be buried without further examination. Thus, the physician has a crucial function that requires a high measure of diligence.

[Typical findings of maltreated children]. / So differenzieren Sie zwischen Unfall und Cewalttat. Indizien der Kindesmisshandlung.

Childhood maltreatment manifests in a variety of forms and the underlying causes are manifold. In contrast to other offences involving physical injury, reporting behavior has, statistically speaking, remained unchanged. Patterns of injury must first be established and documented, and this involves a complete examination of the child's body. Depending on the constellation of findings, a radiological diagnosis is usually necessary. When all the findings have been collected, the further steps to be taken--where indicated a report to the police--must be discussed. All the evidence must be recorded, and photos obtained of all externally visible injuries before they fade. It is not the task of the physician to develop criminalistic ambitions, for example, by grilling (a parent) on the cause of the injuries. However, he/she has a duty to do everything necessary to protect the well-being of the child.

A template for broad consent in biobank research. Results and explanation of an evidence and consensus-based development process.

BACKGROUND: Biobanks increasingly presume long-term storage of biomaterials and data that shall be used for future research projects which are today unspecified. Appropriate consent documents for sample donors must therefore explain the breadth of consent and other elements of the biobank governance framework. Recent reviews demonstrated high variability in what issues these documents mention or not and how the issues are explained. This might undermine the protection of sample donors, complicate networked biobank research, create research waste and impact on public trust. METHODS: A systematic analysis of international research guidelines and existing broad consent templates was performed. Based on this information an interdisciplinary expert group from the AKMEK (Permanent Working Party of German RECs) developed a draft template and organized a comprehensive stakeholder consultation. After revision the final template was consented by all 53 German RECs. RESULTS: This paper briefly explores the spectrum of potentially relevant issues for broad consent forms. It then elaborates the template and how it was designed to be applicable in different types of biobanks. DISCUSSION: To further improve the validity and applicability of broad consent forms in biobank and other big data research, practice evaluations are needed. We hope that in this regard the presented template supports the development of new consent forms as well as the evaluation and revision of existing ones.

[Paternity tests--current methods and legal background]. / Vaterschaftstests: Wie sie funktionieren und worauf es vor Gericht ankommt: Meins oder seins?

Paternity expertises are established on the basis of so-called STR (short-tandem repeat) polymorphisms. As a rule, they are requested by a judge for use as evidence in the clarification of the question of fathershaft in civil court cases. In addition to this, however, they are being requested more and more frequently by private persons, in the majority of cases with the aim of challenging presumptive fathershaft. In this latter case, however, it must be noted that when a minor is involved, the consent of the person who has the care and custody of the child must be available.

Testosterone and androstenedione concentrations in human testis and epididymis during the first two years of life.

Testosterone and androstenedione were measured in testicular and epididymal tissue of 37 previously healthy infants between 1 and 24 months of age who died suddenly. In half of the patients elevated plasma levels of cortisol and androstenedione suggested preterminal stress. Plasma testosterone levels, however, did not differ from those in healthy infants. Testicular testosterone concentrations were maximal in boys from 1-3 months of age (median, 36.6 ng/g; range, 7-380 ng/g) with peak values similar to those found in pubertal or even adult testes. Thereafter testicular testosterone concentrations decreased and after the age of 6 months all values were below 12.5 ng/g, which corresponds to the low normal range of older prepubertal boys. Plasma testosterone and testicular testosterone correlated significantly (P less than 0.001). On average the testicular concentrations were 36.4 times higher than the corresponding plasma concentrations. Testicular androstenedione was low but correlated significantly with testicular testosterone (P less than 0.001). Epididymal testosterone concentrations were surprisingly high (1-3 months: median, 10.3 ng/g; range, 4-42.7 ng/g) and averaged 30% of the testicular testosterone concentration. Thus, epididymal testosterone concentrations were significantly higher than the circulating plasma testosterone levels, indicating the capacity of the infant epididymis to accumulate androgens. These findings suggest that high local testosterone concentrations during early infancy are important not only for the testis itself but particularly for the developing epididymis.

Contribution of the adrenal gland to the production of androstenedione and testosterone during the first two years of life.

Androstenedione and testosterone were measured in whole adrenal glands of 56 previously healthy boys who died suddenly between birth and 2 yr of age. In each adrenal gland, the concentration of androstenedione considerably exceeded that of testosterone. The highest concentrations were found during the first week of life (median, 295 ng/g; range, 98-320 ng/g). Thereafter, values decreased rapidly until the end of the first year of life (median, 10 ng/g; range, 4.4-22.7 ng/g). Adrenal testosterone concentrations averaged 15% of those of androstenedione in the same gland and similarly decreased until the end of the first year. The decrease of adrenal androgen concentrations paralleled the involution of the fetal adrenal zone. A close correlation existed between the concentration of androstenedione in adrenal tissue and plasma. However, no correlation existed between adrenal and plasma testosterone. When the adrenals and testes of the same infant were compared, there was 10 times more androstenedione in the adrenals than in the testes during the first 2 yr of life. The testes contained more testosterone than the adrenals only during the first 4 months. Thus, in infant boys the adrenals are the main source of androstenedione during the first 2 yr. After the sixth month of life, they also are the main source of testosterone.

Analysis of human sodium iodide symporter gene expression in extrathyroidal tissues and cloning of its complementary deoxyribonucleic acids from salivary gland, mammary gland, and gastric mucosa.

The ability to concentrate iodide is a fundamental property of normally functioning thyroid tissue and represents the first step in the production of thyroid hormones. Iodide uptake has been demonstrated in various extrathyroidal tissues, including salivary gland, gastric mucosa, and lactating mammary gland. Recently, cloning and molecular characterization of the human sodium iodide symporter (hNIS) have been reported; however, the patterns of hNIS gene expression in human tissues have remained unidentified. To examine the profiles of human hNIS gene expression in various normal human tissues, we performed high-stringency Northern blot analysis using a 32P-labeled hNIS-specific complementary DNA (cDNA) probe (nucleotides 1184-1667). To detect rare hNIS transcripts in small tissue samples, RT-PCR was performed with a pair of hNIS-specific oligonucleotide primers designed to amplify a portion (nucleotides 1184-1667) of the hNIS gene. hNIS-specific transcripts were confirmed by Southern hybridization using a digoxigenin-labeled internal hNIS-specific oligonucleotide probe (nucleotides 1460-1477). To monitor cDNA integrity and quantity, and to rule out DNA contamination and illegitimate transcription, all samples were coamplified with two pairs of intron-spanning primers designed to amplify fragments of the human beta-actin and thyroglobulin genes, respectively. Using Northern blot analysis, hNIS transcripts of approximately 4 kb were detected in thyroid gland and parotid gland but not in a broad range of endocrine and nonendocrine tissues. RT-PCR and Southern hybridization revealed hNIS gene expression in thyroid gland, salivary gland, parotid gland, submandibular gland, pituitary gland, pancreas, testis, mammary gland, gastric mucosa, prostate and ovary, adrenal gland, heart, thymus, and lung. By contrast, hNIS transcripts were not detected in normal orbital fibroblasts, colon, and nasopharyngeal mucosa. To further analyze hNIS gene sequences in parotid gland, mammary gland, and gastric mucosa, the EXPAND High Fidelity PCR System and three sets of overlapping NIS oligonucleotide primers were used for amplification and cloning. The resulting PCR products were subcloned into pBluescript-SKII(-)vector, and at least two independent cDNA clones derived from each tissue were subjected to automated sequencing. The nucleotide sequences of hNIS cDNA derived from parotid gland, mammary gland, and gastric mucosa revealed full identity with the recently published human thyroid-derived NIS cDNA sequence. In conclusion, our results demonstrate markedly variable levels of hNIS gene expression in several extrathyroidal tissues. Although the physiological role of hNIS in these tissues awaits further study, our results suggest that the capacity to actively transport iodine may be a feature common to several secretory and endocrine tissues. The diminished capacity to transport and concentrate iodide in extrathyroidal tissues (such as parotid gland, mammary gland, and gastric mucosa), compared with thyroid gland, does not seem to be caused by an altered primary structure of the hNIS cDNA. Variability of NIS gene expression levels in normal extrathyroidal tissues may rather be caused by differences in NIS gene transcriptional activity. Further studies will address this hypothesis and examine the mechanisms of tissue-specific regulation of NIS gene expression.

Expression of the insulin-like growth factor-II/mannose-6-phosphate receptor in multiple human tissues during fetal life and early infancy.

The insulin like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor has been detected in many cells and tissues. In the rat, there is a dramatic developmental regulation of IGF-II/M6P receptor expression, the receptor being high in fetal and neonatal tissues and declining thereafter. We have systematically studied the expression of the human IGF-II/M6P receptor protein in tissues from 10 human fetuses and infants (age 23 weeks gestation to 24 months postnatal). We have asked 1) whether there is differential expression among different organs, and 2) whether or not the human IGF-II/M6P receptor is developmentally regulated from 23 weeks gestation to 24 months postnatal. Protein was extracted from human tissues using a buffer containing 2% sodium dodecyl sulfate and 2% Triton X-100. Aliquots of the protein extracts were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting using an anti-IGF-II/M6P receptor antiserum (no. 66416) and 125I-protein A or an immunoperoxidase stain. IGF-II/M6P receptor immunoreactivity was detected in all tissues studied with the highest amount of receptor being expressed in heart, thymus, and kidney and the lowest receptor content being measured in brain and muscle. The receptor content in ovary, testis, lung, and spleen was intermediate. The apparent molecular weight of the IGF-II/M6P receptor (220,000 kilos without reduction of disulfide bonds) varied among the different tissues: in brain the receptor was of lower molecular weight than in other organs. Immunoquantitation experiments employing 125I-protein A and protein extracts from human kidney at different ages revealed a small, albeit not significant, difference of the receptor content between fetal and postnatal tissues: as in other species, larger amounts of receptor seemed to be present in fetal than in postnatal organs. In addition, no significant difference of the receptor content between human fetal liver and early postnatal liver was measured employing 125I-protein A-immunoquantitation in three fetal and five postnatal liver tissue samples. The distribution of IGF-binding protein (IGEBP) species, another abundant and major class of IGF binding principles, was also measured in human fetal and early postnatal lung, liver, kidney, muscle, and brain using Western ligand blotting with 125I-IGF-II: as with IGF-II/M6P receptor immunoreactivity there was differential expression of the different classes of IGFBPs in the various organs.(ABSTRACT TRUNCATED AT 400 WORDS)

Estrone and estradiol concentrations in human ovaries, testes, and adrenals during the first two years of life.

To determine the origin of estrogens in infant blood, we measured estrone (E1) and estradiol (E2) in the gonads of 50 girls and 64 boys who died suddenly between birth and 2 yr of age as well as in the adrenals of 18 of these infant girls and 16 of the boys. In the adrenals, E1 [median, 2.8 ng/g (10.4 pmol/g); range, 1.1-4.8 ng/g (4.1-17.8 pmol/g)] and E2 [median, 3.0 ng/g (10.9 pmol/g); range, 1.2-5.3 ng/g (4.4-19.5 pmol/g)] were found in similar concentrations and were independent of age and sex. In the gonads, E2 was the major estrogen, but the concentrations differed markedly between the sexes; E2 exceeded E1 almost 10-fold in the ovaries and 2-fold in the testes. On the average, the gonads of the infant girls had 5 times more E2 and 2 times more E1 than those of the boys. As in plasma, E2 concentrations were highest in the ovaries of 1- to 6-month-old girls [median, 10.5 ng/g (38.5 pmol/g); range, 1.1-55.1 ng/g (4.0-202.0 pmol/g)] and in testes of 1- to 3-month-old boys [median, 1.8 ng/g (6.6 pmol/g); range, 0.6-6.4 ng/g (2.3-23.5 pmol/g)]. Ovarian E2 concentrations declined to less than 3.0 ng/g (11.0 pmol/g) by the end of the first year of life, and testicular E2 declined to less than 1.0 ng/g (3.7 pmol/g) after only 6 months of age. Gonadal estrogen concentrations paralleled changes in gonadal morphology. Ovarian weights varied in a pattern of rise and fall similar to that of ovarian E2 concentrations; the biggest ovaries contained multiple macroscopic cysts. Testicular E2 closely correlated with Leydig cell development and testicular testosterone concentrations. We infer, therefore, that the surge of plasma E2 in infant girls originates from ovarian follicles and that of boys from testicular Leydig cells, and that these both occur as a result of the postnatal surge in gonadotropin secretion. The basal plasma E1 and E2 pool, however, is derived from the adrenals and remains at a comparatively constant level in both sexes.

Changes in trabecular bone, hematopoiesis and bone marrow vessels in aplastic anemia, primary osteoporosis, and old age: a comparative histomorphometric study.

Retrospective histologic analyses of bone biopsies and of post mortem samples from normal persons of different age groups, and of bone biopsies of age- and sex-matched groups of patients with primary osteoporosis and aplastic anemia show characteristic age dependent as well as pathologic changes including atrophy of osseous trabeculae and of hematopoiesis, and changes in the sinusoidal and arterial capillary compartments. These results indicate the possible role of a microvascular defect in the pathogenesis of osteoporosis and aplastic anemia.

Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide.

Serotonergic dysfunction has been implicated in the pathophysiology of affective disorders and suicidality. Especially the density of the 5-HT2A receptor was claimed as being increased in suicidality, proposed as an adaptive upregulation due to reduced serotonergic transmission. Recent studies have shown an association of allele C of the 5-HT2A-T102C polymorphism with suicidal ideation in patients with major depression. The purpose of this study was to test whether this proposed marker indicates susceptibility not only to suicidal ideation in depressed patients but also to suicidality as a syndrome. We investigated the 5-HT2A-T102C polymorphism in 131 suicide victims with unknown underlying psychiatric diagnoses, 84 patients with major depression with or without suicidal ideation, and 125 healthy controls. We were unable to find any association of genotype or allele frequencies to major depression, suicidal ideation, or suicide as a syndrome. Thus, our results suggest that this polymorphism may not commonly be involved in the susceptibility to suicidality. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:831-835, 2000.

X-ray microanalysis of crystalline material in the liver of a narcotics user.

A 22-year-old athlete, who had had intravenous injections of narcotics in the past, developed a viral hepatitis with markedly altered liver enzyme values. Studies revealed evidence of a virtual cure of hepatitis B virus and a current infection with delta agent. Liver biopsy showed a mixed-cell portal inflammation and doubly refractile crystalline particles. These particles were shown by energy-dispersive x-ray microanalysis to contain calcite, silica, talc, and a variety of elements including Al, P, S, Cl, K, Ti, Cr, Fe, Ni, Br, Yb, Os, Ir, and a trace U. The predominance of Ca-containing compounds suggested that the foreign material was present as a result of the chemical preparation of the narcotic or as a narcotic diluent. The potential for pathologic alteration by the various substances is discussed. These observations support the idea of particulate-induced hepatic disease advanced previously by others.

Monoclonal antibodies against human astrocytomas and their reactivity pattern.

The establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from BALB/c mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 X 10(6) chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner.

Quantitative investigations on the human entorhinal area: left-right asymmetry and age-related changes.

The total nerve cell numbers in the right and in the left human entorhinal areas have been calculated by volume estimations with the Cavalieri principle and by cell density determinations with the optical disector. Thick gallocyanin-stained serial frozen sections through the parahippocampal gyrus of 22 human subjects (10 female, 12 male) ranging from 18 to 86 years were analysed. The laminar composition of gallocyanin (Nissl)-stained sections could easily be compared with Braak's (1972, 1980) pigmentoarchitectonic study, and Braak's nomenclature of the entorhinal laminas was adopted. Cell-sparse laminae dissecantes can more clearly be distinguished in Nissl than in aldehydefuchsin preparations. These cell-poor dissecantes, lamina dissecans externa (dis-ext), lamina dissecans 1 (dis-1) and lamina dissecans 2 (dis-2), were excluded from nerve cell number determinations. An exact delineation of the entorhinal area is indispensable for any kind of quantitative investigation. We have defined the entorhinal area by the presence of pre-alpha cell clusters and the deeper layers of lamina principalis externa (pre-beta and gamma) separated from lamina principalis interna (pri) by lamina dissecans 1 (dis-1). The human entorhinal area is quantitatively characterized by a left-sided (asymmetric) higher pre-alpha cell number and an age-related nerve cell loss in pre as well as pri layers. At variance with other CNS cortical and subcortical structures, the neuronal number of the entorhinal area appears to decrease continuously from the earliest stages analysed, although a secular trend has to be considered. The asymmetry in pre-alpha cell number is discussed in the context of higher human mental capabilities, especially language.

The mechanisms of stone fragmentation in ESWL.

Currently, several mechanisms of kidney stone fragmentation in extracorporal shockwave lithotripsy (ESWL) are under discussion. As a new mechanism, the circumferential quasistatic compression or "squeezing" by evanescent waves in the stone has been introduced. In fragmentation experiments with self-focussing electromagnetic shock-wave generators with focal diameters comparable to or larger than the stone diameter, we observed first cleavage surfaces either parallel or perpendicular to the wave propagation direction. This is in agreement with the expectation of the "squeezing" mechanism. Because, for positive pulse pressures below 35 MPa and stones with radii of 15 mm or smaller, cleavage into only two fragments was observed, we developed a quantitative model of binary fragmentation by "quasistatic squeezing." This model predicts the ratio of the number of pulses for the fragmentation to 2-mm size and of the number of pulses required for the first cleavage into two parts. This "fragmentation-ratio" depends linearly alone on the stone radius and on the final size of the fragments. The experimental results for spherical artificial stones of 5 mm, 12 mm and 15 mm diameter at a pulse pressure of 11 MPa are in good agreement with the theoretical prediction. Thus, binary fragmentation by quasistatic squeezing in ESWL as a new efficient fragmentation mechanism is also quantitatively verified.