Digital breast tomosynthesis changes management in patients seen at a tertiary care breast center.

Objectives. To study factors that predict changes in management with digital breast tomosynthesis (DBT). Methods. The Institutional Review Board approved this HIPAA compliant study. 996 patients had DBT with full field digital mammography (FFDM). Univariate analysis evaluated predictors of management change and cancer detection. Results. DBT changed management in 109 of 996 (11%); 77 (71%) required less imaging. Recalled patients after abnormal FFDM screen were most likely to have management change-25% (24 of 97 patients) compared to 8% (13/163) of symptomatic patients and 10% (72/736) of screening patients (P < 0.001). Dense breasted patients had a higher likelihood of having DBT change management: 13% (68/526) compared to 9% (41/470) (P = 0.03). Of the 996 patients, 19 (2%) were diagnosed with breast cancer. 15 cancers (83%) were seen on FFDM and DBT; 3 (17%) were diagnosed after DBT (0.3%, 95%CI: 0.1-0.9%). One recurrence was in the skin and was not seen on DBT nor was it seen on FFDM. The increase in cancer detection rate was 17% for asymptomatic patients, 0% for symptomatic patients, and 100% for recalled patients. Conclusions. DBT increased cancer detection rate by 20% and decreased the recall rate in 8-25%. Advances in Knowledge. DBT led to a doubling of the cancer detection rate in recalled patients.

Fatal outcome of a sand aspiration.

Although extensive deep aspiration of sand, gravel, or dirt is a very rare incident, its consequences may be severe ranging from the necessity of immediate intensive care to death. Cases reported so far were due to external causes such as cave-ins, near drowning, or being buried under sand masses. We report a case of a 2 1/2-year-old boy who ingested sand while playing in a sandbox with his older brother. Despite early resuscitation and endotracheal intubation efforts, he died subsequently showing clinical signs of asphyxia due to airway obstruction. Autopsy revealed sand masses obstructing the trachea and lobar bronchi of both lungs as well as brain edema, while no signs of blunt trauma, forced sand ingestion, or preexisting medical conditions were found. This case demonstrates that fatal self-administered sand aspiration may occur in early childhood. The pathophysiology of the lethal outcome with regard to the physical properties of sand and implications for the clinical assessment of emergency situations are discussed.

Medicolegal assessment of blood transfusion errors--an interdisciplinary challenge.

Given a current total incidence of erroneously administered blood transfusions of 1:12,000-1:36,000 (AB0 incompatible 1:38,000), the percentage of lethal outcomes ranges between 2 and 5%; i.e. the sole fact of an erroneous transfusion does not mandatorily result in a causal connection with lethal outcome, which can give rise to problems in the medicolegal assessment. We report on the conception and results of a novel interdisciplinary approach to assess the lethal significance of blood transfusion errors. Besides autopsy, histological investigation and immunohistochemical detection of AB0 incompatible foreign red blood cells in autopsy specimens, transfusion medicine investigations offer the opportunity to assess several immunohaematologic features. We assessed the immunohaematologic gel card ("microcolumn") technique for suitability in the forensic assessment of an AB0 incompatible transfusion incident in a septic patient, who had had no history of previous blood transfusions, with lethal outcome. After such an erroneous transfusion had been simulated in vitro, pre-transfusion and cadaver patient blood samples (p.m. interval: 3 days) were analysed. Amongst other things, IgG-loaded erythrocytes were detected in pre- and post-transfusion samples; the presence of irregular antibodies directed against blood group antigens and anti-A or anti-B isoagglutinins, respectively, especially in the pre-transfusion sample was ruled out. Besides the demonstration of AB0 incompatible red blood cells in the cadaver blood sample, blood group incompatibilities other than AB0 were excluded. With regard to the cause of death, in synopsis with autopsy findings and clinical symptoms, the results did not allow for a final discrimination between the impact of the pre-existing septic inflammatory response syndrome and sepsis, respectively, and potential lethal effects of a (haemolytic) transfusion reaction. Besides pre- and post-transfusion compatibility testing in clinical transfusion medicine as required by German National Guidelines, the reported immunohaematologic investigations offer an important supportive tool for the forensic assessment of lethal erroneous transfusions and investigation of blood samples of survivors of transfusion incidents as well. Besides established morphological techniques, they allow for a certain evaluation of the pathophysiological impact of transfusion incidents as well as a diversified assessment of immunohaematologic features beyond the AB0 system.

An unusual case of thermal injuries with a hot glue gun. Deliberate self-harm or maltreatment?

Assessing injuries in forensic medicine casework, examiners are often confronted with the question of self-infliction versus third parties' influence, respectively, deliberate self-harm versus maltreatment. We report the case of a 40-year-old male who presented with numerous partially healed thermal injuries of different age. These burns were shaped like capital letters and little circles, which were arranged in lines in a regular form. The lesions were found on the whole body with exclusion of face, genitals, hands and feet. Furthermore, four bitemarks at the right shoulder were noted. Investigations revealed that the man had been abused by his 25-year-old wife (presumably a borderline personality disorder patient) for at least 1 year. In addition to another series of abuses, the woman may have inflicted the shaped burns with a hot glue gun as punishment for breaking certain "rules" she had established. When assessing injuries of patients in forensic medicine, several considerations regarding etiology have to be taken into account. In principle, the victim's testimony, the anamnesis, the police investigation results and the findings from the forensic physical examination have to be balanced against each other. The injury pattern in the present case showed contradictory single characteristics both of deliberate self-harm and of maltreatment. After forensic analysis, it was assessed as injuries inflicted by an assistant with the patient's consent.

Laryngohyoid fractures after agonal falls: not always a certain sign of strangulation.

Haemorrhagic fractures of the thyroid cartilage and hyoid bone are frequently observed in cases of strangulation and often regarded as evidence for an assault against the neck. In contrast, two cases of laryngohyoid fractures after agonal falls in prone position are presented to draw attention to alternative causes of these injuries with special regard to practical medicolegal casework. A 45-year-old man collapsed at a fairground and died after unsuccessful resuscitation. He showed excoriations at his elbows and right knee, a crush injury at the mentum and his mandibular front teeth were knocked out. The upper parts of the chest and the head showed blue discolouration as a marked sign of congestion due to heart failure. The right coronary artery (RCA) was completely obturated by a 5 cm long post-stenotic thrombus with subsequent myocardial infarction of the lateral part of the left ventricle. Both superior horns of the thyroid cartilage were fractured with surrounding haemorrhage, the skin and muscles of the neck uninjured. In the second case, a 63-year-old woman with a mobility handicap had fallen from a 2m high lifting platform and was found in prone position with her wheelchair on her. Resuscitation efforts were not successful. Autopsy showed signs of blunt external force against head, neck, chest and limbs. Examination of the neck revealed haemorrhage of the right sternocleidomastoid muscle, both superior horns of the thyroid cartilage were fractured, as well as the hyoid bone, with slight haemorrhage of the surrounding soft tissue and mucosa. On the same level, the fifth intervertebral disk was ruptured, without any injury of the spinal cord. These cases demonstrate that laryngohyoid fractures should not be overestimated as unequivocal indication of neck compression and may well be caused by falls, even at ground level.

Two simultaneous suicidal gunshots to the head with robbed police guns.

The suicidal infliction of two gunshot wounds to the head represents a critical issue for medicolegal investigation. In principle, simultaneous infliction with two firearms or third parties' involvement, i.e. two consecutive gunshots, have to be considered. We report for the first time on a case of suicidal infliction of two simultaneous gunshots to the head (oral, temporal) with Action 4 expanding ammunition. A male had robbed two service guns and committed suicide thereafter under the influence of high-dose alcohol and cocaine. Interestingly, Action 4 ammunition had been used, leading to an uncommon gunshot wound morphology and extensive backspatter. At the scene, these findings caused confusion; moreover, the number of gunshot wounds was unclear, until autopsy revealed two gunshot wounds to the head, which had obviously been inflicted simultaneously. Expanding ammunition like QD-PEP and Action 4, used by several German federal state police forces, can cause an atypical gunshot wound morphology, most probably due to its peculiar deformation behaviour. Investigators should be careful when interpreting gunshot wound morphology at the scene after usage of such expanding ammunition. With regard to reconstruction in cases of two gunshot wounds to the head and two guns at the scene, two simultaneous gunshots should be taken into consideration.

Spinal epidural haematoma after blunt trauma to the neck and hyperflection of the cervical spine.

Spinal epidural haematomas (sEDH) can be regarded as rare events, in principle a spontaneous and a traumatic aetiology can be distinguished. Spontaneous spinal epidural haematomas can arise, e.g. from vascular malformations, coagulopathies, etc. On the other hand, traumatic sEDH are related to, e.g. spinal trauma or intraoperative vascular injuries. With regard to clinical significance, spinal epidural haematomas accompanied by transient mild neurological symptoms up to lethal outcomes have been observed. We report on a 53-year-old male alcoholic who was found in the kitchen of his asylum in a grotesquely fixed body position, with his head and cervical spine in a maximum anteflected position. A general practitioner had ruled for a non-natural manner of death due to "broken neck" and alcohol intoxication, therefore, the prosecution authorities called for a medicolegal autopsy. At autopsy, paravertebral soft tissue haemorrhage in between the shoulder blades was disclosed. Furthermore, a spinal epidural haematoma, extending from the foramen magnum down to the middle portion of the thoracic spine was found. No fractures of vertebrae nor lesions of spine ligaments or bleedings of intervertebral discs were found. Blood alcohol concentration was determined 1.92 g/l and urine alcohol concentration was 1.76 g/l. Further morphological findings were cerebral oedema and cardiac hypertrophy; the urinary bladder was found filled to bursting. Neuropathological investigations confirmed the presence of the spinal epidural haematoma and assigned lethal significance to this finding. There were no histological signs of axonal injury. Reconstruction revealed that when sitting on a chair in a drunk condition, the individual's upper part of the body had fallen backwards in the corner and subsequently got stuck with maximum anteflection of the head and cervical spine, causing rupture of vessels and spinal epidural haematoma. Acute respiratory failure caused by impairment of the phrenic nerve following spinal epidural haematoma with potential synergism of alcohol intoxication was ascertained as the cause of death.

[Causes of death in nursing homes--a retrospective autopsy study]. / Todesursachenspektrum im Altenheim im Spiegel eines rechtsmedizinischen Sektionsgutes.

Autopsies from 34 fatalities in nursing homes covering a 10-year period (1991-2000) were retrospectively analyzed with regard to criminal investigative issues, causes of death and relevance of the forensic medical findings for the outcome of the criminal investigations. The material consisted of 22 females and 12 males, with the ages ranging from 62 to 102. The allegations to be investigated comprised wrongful death, improper nursing, medical maltreatment, suspicion of poisoning and the causal relationship between falls and the occurrence of death. The manner of death, respectively cause of death encountered included 21 deaths from natural cause (coronary insufficiency, pneumonia), 9 accidental deaths (hypothermia, choking, scalding burns and injuries due to fall) and 4 cases which remained undetermined. In 30 out of 34 cases, the cause of death was unequivocally established. In every case, the medicolegal investigation provided adequate evidence for the legal assessment. Of particular significance was the exclusion of a causal relationship between falls and the occurrence of death. Without exception, all investigations failed to uncover criminal causes for death in this sample.

Typical versus atypical presentation of obturator hernia.

Although it is a rare occurrence among all pelvic hernias diagnosed the obturator hernia continues to be a diagnostic challenge for surgeons today. These patients, who often have multiple concurrent medical problems, are subject to high morbidity and mortality rates resulting from late presentation and delayed surgical intervention. The vast majority of patients with obturator hernias are admitted with signs and symptoms of intestinal obstruction, namely anorexia, nausea, vomiting, constipation, and distension of 2 to 3 days' duration. In this paper, however, we highlight a small subset of obturator hernia patients who present without obstructive symptoms and do well after elective repair. The case reports that follow serve to compare and contrast two very different presentations of this surgical problem.

Identification of a metaplastic cell lineage associated with human gastric adenocarcinoma.

Metaplastic cell lineages arising in response to chronic injury are precursors for the evolution of dysplasia and adenocarcinoma. Although a subtype of intestinal metaplasia has been associated with gastric adenocarcinoma, the link between this lineage and the evolution of gastric adenocarcinoma has remained unclear. Wang et al (1998) have reported that an aberrant metaplastic cell lineage with morphological characteristics similar to Brunner's glands of the duodenum develops in the fundic mucosa of mice infected with Helicobacter felis. This metaplastic lineage expresses the trefoil peptide spasmolytic polypeptide (SP). Given the epidemiological association of Helicobacter species infection with gastric cancer, we hypothesized that this SP-expressing metaplastic (SPEM) lineage may represent a precursor to or appear commensurate with gastric adenocarcinoma. The SPEM lineage was present in 68% of fundic biopsies from patients with fundic Helicobacterpylori-associated gastritis, but was absent in biopsies of fundic mucosa from patients without H. pylori infection. In a review of archival samples from 22 resected gastric adenocarcinomas, we found the SPEM lineage in 91% of cases, typically located in mucosa adjacent to the carcinoma or areas of dysplasia. Importantly, 59% of resections showed SP immunoreactivity within dysplastic cells. These data indicate a strong association of the SPEM lineage with both chronic H. pylori infection and gastric adenocarcinoma.

AKAP350, a multiply spliced protein kinase A-anchoring protein associated with centrosomes.

Protein kinase A-anchoring proteins (AKAPs) localize the second messenger response to particular subcellular domains by sequestration of the type II protein kinase A. Previously, AKAP120 was identified from a rabbit gastric parietal cell cDNA library; however, a monoclonal antibody raised against AKAP120 labeled a 350-kDa band in Western blots of parietal cell cytosol. Recloning has now revealed that AKAP120 is a segment of a larger protein, AKAP350. We have now obtained a complete sequence of human gastric AKAP350 as well as partial cDNA sequences from human lung and rabbit parietal cells. The genomic region containing AKAP350 is found on chromosome 7q21 and is multiply spliced, producing at least three distinct AKAP350 isoforms as well as yotiao, a protein associated with the N-methyl-D-aspartate receptor. Rabbit parietal cell AKAP350 is missing a sequence corresponding to a single exon in the middle of the molecule located just after the yotiao homology region. Two carboxyl-terminal splice variants were also identified. Both of the major splice variants showed tissue- and cell-specific expression patterns. Immunofluorescence microscopy demonstrated that AKAP350 was associated with centrosomes in many cell types. In polarized Madin-Darby canine kidney cells, AKAP350 localized asymmetrically to one pole of the centrosome, and nocodazole did not alter its localization. During the cell cycle, AKAP350 was associated with the centrosomes as well as with the cleavage furrow during anaphase and telophase. Several epithelial cell types also demonstrated noncentrosomal pools of AKAP350, especially parietal cells, which contained multiple cytosolic immunoreactive foci throughout the cells. The localization of AKAP350 suggests that it may regulate centrosomal and noncentrosomal cytoskeletal systems in many different cell types.

Membrane potassium channels and human bladder tumor cells. I. Electrical properties.

These experiments were conducted to determine the membrane K+ currents and channels in human urinary bladder (HTB-9) carcinoma cells in vitro. K+ currents and channel activity were assessed by the whole-cell voltage clamp and by either inside-out or outside-out patch clamp recordings. Cell depolarization resulted in activation of a Ca(2+)-dependent outward K+ current, 0.57 +/- 0.13 nS/pF at -70 mV holding potential and 3.10 +/- 0.15 nS/pF at 30 mV holding potential. Corresponding patch clamp measurements demonstrated a Ca(2+)-activated, voltage-dependent K+ channel (KCa) of 214 +/- 3.0 pS. Scorpion venom peptides, charybdotoxin (ChTx) and iberiotoxin (IbTx), inhibited both the activated current and the KCa activity. In addition, on-cell patch recordings demonstrated an inwardly rectifying K+ channel, 21 +/- 1 pS at positive transmembrane potential (Vm) and 145 +/- 13 pS at negative Vm. Glibenclamide (50 microM), Ba2+ (1 mM) and quinine (100 microM) each inhibited the corresponding nonactivated, basal whole-cell current. Moreover, glibenclamide inhibited K+ channels in inside/out patches in a dose-dependent manner, and the IC50 = 46 microM. The identity of this K+ channel with an ATP-sensitive K+ channel (KATP) was confirmed by its inhibition with ATP (2 mM) and by its activation with diazoxide (100 microM). We conclude that plasma membranes of HTB-9 cells contain the KCa and a lower conductance K+ channel with properties consistent with a sulfonylurea receptor-linked KATP.

Does intervention improve the natural course of glomus tumors? A series of 108 patients seen in a 32-year period.

To acquire more insight into the results of treatment versus the "natural" course of glomus tumors, we studied the clinical data of 108 patients, in 58 of whom the disease was hereditary. During a period of 32 years (1956 to 1988), 175 tumors were diagnosed: 52 glomus jugulotympanic tumors, 32 vagal body tumors, and 91 carotid body tumors. The results of radical surgical treatment were disappointing for tumors located at the skull base, ie, nonradical in 59% (n = 23) of the cases, but very good for the carotid body tumors, for which 96% (n = 68) radical excision was achieved. Moreover, surgery at the level of the skull base dramatically increased morbidity, since it frequently induced cranial nerve palsy. During the follow-up period (maximal observation time 32 years, mean 13.5 years) none of the patients died of residual or recurrent tumor or developed distant metastases, irrespective of the mode and outcome of treatment. When these results are combined with the results of pedigree analysis, a realistic approximation of the "natural" course of the disease for both hereditary and nonfamilial tumors can be made. The results raise the question of whether this natural behavior is really improved by intervention. We conclude that removal of carotid body tumors and solitary vagal body tumors should be considered in order to prevent future morbidity. However, for skull base and bilateral glomus tumors a more conservative monitored "wait and see" policy can be sensible and should be considered in any proposal for treatment of head and neck paragangliomas.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA flow cytometry of hereditary and sporadic paragangliomas (glomus tumours).

Paragangliomas (glomus tumours) are benign, hypervascular tumours which in general are treated by surgical excision. The indication for treatment of these often slow-growing tumours needs additional criteria for predicting tumour progressiveness. For this reason the nuclear DNA content of 99 paragangliomas, 65 of them originating from patients with a positive family history, was analysed by flow cytometry. Unequivocal evidence of DNA aneuploidy was found in 37% of these clinically and histologically benign tumours, the average duration of follow up amounting to at least 10 years. The DNA index of the aneuploid tumours ranged from 0.90 to 2.03. No correlation was found between DNA ploidy and familiality or between DNA content and clinical criteria indicative of tumour progression, which means that DNA ploidy of these tumours cannot serve as a predictor for an expected growth pattern or familiality. DNA aneuploidy in hereditary and sporadic paragangliomas is not clinically related to malignancy, but indicates that these tumours are true neoplasias cytogenetically.

A longitudinal electrocochleographic study of a case of long-standing bilateral Lermoyez's syndrome.

An 18-year follow-up of a case of bilateral Lermoyez's syndrome is presented. The left ear having reached a stabilized hearing loss about 9 years after the onset of the disease, the right ear, apart from some isolated early periods of hearing loss, started to show the full extent of clinical symptoms after about 16 years. Electrocochleographic observations are presented. Studies were performed twice in the right ear during a period of strongly fluctuating hearing thresholds, once in an impaired and once in a relatively good condition. Electrocochleography of the stabilized left ear was performed as well. The data are compared with electrocochleographical observations in the left ear in its early fluctuating stage. Variation of cochlear physiological data during the fluctuating stage of the disease shows remarkable correspondence between the two ears. The stabilized Lermoyez ear is shown to have developed considerable hair cell loss, but may still have preserved its endolymphatic hydrops. These findings in Lermoyez's syndrome fit well into the observations reported in patients with Menière's disease.

Genomic imprinting in hereditary glomus tumours: evidence for new genetic theory.

A study based on fifteen pedigrees showed that familial glomus tumours are inherited almost exclusively via the paternal line, a finding inconsistent with autosomal dominant transmission. The results can be explained in terms of the genomic imprinting hypothesis--the maternally derived gene is inactivated during female oogenesis and can be reactivated only during spermatogenesis. Genomic imprinting may have considerable implications for genetic counselling with respect to glomus tumours and also for the understanding of other hereditary diseases.

Lermoyez's syndrome. A follow-up study in 12 patients.

Clinical studies were performed in 12 patients with the Lermoyez syndrome during a close follow-up of 2 to 31 years. The nature and temporal sequences of the symptoms of these patients are described. The incidence of Lermoyez's syndrome, as compared with Meniere's disease, is almost 18%. This is much higher than usually is assumed. In 6 out of 12 patients typical Meniere attacks were found besides their Lermoyez attacks. Almost every one of the 12 patients showed, besides the Lermoyez attacks, also hearing fluctuations without vertigo, and vertigo without hearing fluctuations. The type of vertigo was usually rotating, often with unsteadiness and in 3 patients dropping attacks were sometimes observed. The typical Lermoyez attack lasted several hours. The preceding hearing loss lasted for days to months. The hearing recovered after the attacks and remained stable for days to months. An improved hearing was noticed within some hours after the vertiginous attack in 9 out of 12 cases. Three patients noticed the hearing improvement already during the attack. In 8 out of 12 cases the disease became bilateral.

Meniere's disease: a long-term follow-up study of hearing loss.

Twenty patients suffering from Meniere's disease or Lermoyez syndrome were studied with respect to the time course of their hearing loss. Careful history-taking as well as repeated audiometry over long time spans (5-20 years) resulted in a longitudinal study of hearing loss at the standard audiometric frequencies. From these time series, correlation coefficients were computed between the changes in both ears at identical frequencies, and for changes in the same ear at different frequencies. Correlations between changes in hearing loss in both ears were more obvious in bilateral Meniere's disease than in unilateral disease. Correlations between changes in hearing loss at different frequencies were also more pronounced in Meniere's disease ears than in normal ears. If was found that recovery of hearing loss after an attack was nearly identical each time it occurred in the same ear, but differed between ears and patients. This deterministic finding in the otherwise random course of the hearing loss as a function of time may be important in deciding what mechanisms cause fluctuating hearing loss in Meniere's disease.