Tumor microcirculation evaluated by dynamic magnetic resonance imaging predicts therapy outcome for primary rectal carcinoma.

Contrast enhanced dynamic studies of malignant tumors performed by computed tomography or magnetic resonance imaging (MRI) are increasingly applied to characterize tumor microcirculation for the prediction of therapy outcome. The aim of our study was to correlate perfusion index (PI) values determined in primary rectal carcinoma before chemoradiation with therapy outcome. In 17 patients with clinically staged T3 primary rectal carcinoma, dynamic MRI was performed before the onset of therapy using an ultrafast T1-mapping sequence. On the basis of the acquired data sets, PI values were calculated on a pixel-by-pixel basis. To characterize the heterogeneity of tumor microcirculation, relative cumulative frequency histograms of PI values within the tumors were computed. Subsequent resection of the tumors allowed correlating PI with histopathological classification. In 12 of 17 patients, T-downstaging as a response to therapy was found, whereas in the remaining 5 patients no therapy response was observed after chemoradiation. A statistically significant difference between both groups was found for the mean PI (P < 0.001; 8.5+/-1.7 ml/min/100 g versus 11.4+/-0.7 ml/min/100 g). Analyzing the cumulative frequency histograms for both groups revealed an optimal discrimination for a P1 value of 12.6 ml/min/100 g. The fraction of pixels in the tumor with PI values larger than 12.6 ml/min/100 g was significantly different (P < 0.001) between therapy-responding (3+/-3.6%) and therapy-nonresponding tumors (21+/-4.3%). The results indicate either a reduced supply of nutrients as well as chemotherapeutic agents attributable to increased shunt flow or highly aggressive tumor cell clusters characterized by increased angiogenic activity. Noninvasive PI measurements by dynamic MRI in rectal carcinoma before therapy seem to be of predictive value for therapy outcome in patients scheduled for preoperative chemoradiation.

A double-hand transplant can be worth the effort!

BACKGROUND: Composite-tissue transplantation offers a new therapeutic option for patients with loss of a hand. Little is known, however, about the long-term outcome after such a transplant with regard to graft function and immunosuppression and its side effects. We here report on our experience with a double-hand transplant performed more than 18 months ago. METHODS: Both distal forearms and hands of an age-, gender-, and size-matched cadaveric donor were transplanted to a 47-year-old policeman 6 years after loss of both hands. He received antithymocyte globulin as induction therapy and tacrolimus, mycophenolate mofetil, and prednisone as maintenance immunosuppression. Ganciclovir and co-trimoxazole were given prophylactically for cytomegalovirus and Pneumocystis carinii infection. A special rehabilitation program based mainly on cognitive therapy was designed and continued for 1 year. RESULTS: Apart from a small area of skin that became necrotic early and some arteriovenous fistulas in the left forearm, which required ligation 6 months after transplantation, there were no surgical complications. One acute rejection episode occurred on day 55 and resolved completely after high-dose steroids and topical tacrolimus. Despite ganciclovir prophylaxis, virus replication was observed. The patient became negative for cytomegalovirus only after additional treatment with foscarnet (Foscavir) and cidofovir. At the end of 18 months, graft function with regard to motility is overall 60% of normal and enables the patient to pursue activities he could not with his myoelectric prostheses. CONCLUSIONS: Excellent long-term results can be achieved with double-hand transplantation. Prerequisites are an appropriate surgical technique, careful immunosuppression, and an extensive rehabilitation program.

Isochromosome 12p and maternal loss of 1p36 in a pediatric testicular germ cell tumor.

Analysis of a pediatric germ cell tumor by conventional cytogenetic investigation and fluorescence in situ hybridization showed consistently the presence of two isochromosomes 12p, loss of the maternal band 1p36, and other numerical and structural chromosome changes. The rearrangements observed resulted mainly from breaks occurring at paracentromeric regions. This report represents the first description of i(12)(p10) in a pediatric testicular embryonal carcinoma.

Comparison of different modes of high-frequency ventilation in surfactant-deficient rabbits.

Various modes of high-frequency ventilation (HFV) have been developed to avoid the disadvantages of conventional mechanical ventilation. In the present study, we examined the hypothesis that high-frequency oscillation (HFO) is superior to high-frequency positive pressure ventilation (HPPV) and combined high-frequency ventilation (CHFV) in surfactant-deficient rabbits. The aim of the ventilator strategy was to adjust the mean airway pressure to 2 cm above critical opening pressure of the inflation limb of the respiratory system pressure volume (P/V) curve, achieve a normal tidal volume (VT) (5 ml/kg body weight) and apply repeated sustained inflations. We studied the effect of these HFV modes on oxygenation, lung mechanics and lung histology in 15 New Zealand White rabbits during a 6-hour experiment. Statistically, the HFO group demonstrated significantly better oxygenation (P < 0.05), lung mechanics (lung stability index: P < 0.05), and better lung tissue histology compared to the HPPV and CHFV groups. In contrast to the HPPV and CHFV groups, the P/V curves of the HFO group showed significant recovery over the 6-hour period after lavage. The lungs of the HFO-treated group had a more uniform distribution of alveoli and less overdistention than the HPPV group (P < 0.002), and less atelectasis than the CHFV group (P < 0.05). The HFO group had less lung injury than the CHFV groups (P < 0.01) and its lungs contained significantly less water than both other groups (P < 0.05). We conclude that the relationship between mean and end-expiratory pressures impacts strongly on both oxygenation and the progression of injury during HFV at the same mean airway pressures. The HFO group showed less acute lung injury than the other ventilatory groups.

A new biliodigestive anastomosis technique to prevent reflux and stasis.

BACKGROUND: The Roux-en-Y procedure for biliodigestive drainage is most widely accepted, but 10% to 15% of patients postoperatively suffer from a blind-loop syndrome or cholangitis due to motility disorders. A new biliodigestive technique is evaluated in a rat model to prevent these complications. METHODS: This experimental study in Wistar rats compares the Roux-en-Y technique with a new biliodigestive anastomosis creating a jejunal loop with luminal occlusion. Clinical parameters, small bowel motility, bacteriologic growth, and liver histopathology were evaluated in native and postoperative animals within a study period of 180 days. RESULTS: Both operative procedures were well tolerated. After 6 months intense fibrosis of the liver and high-grade purulent cholangitis were observed in animals in the Roux-en-Y group. In these animals enterobacter and enterococci overgrowth was found. Myoelectric small bowel recordings revealed significant impairment of slow-wave frequency, aboral velocity, and action potentials (percentage of phase III) in Roux-en-Y animals. CONCLUSIONS: Motility disorders after conventional Roux-en-Y biliodigestive anastomosis are pivotal for histomorphological damage and infectious findings and can be prevented by using the new technique to create a jejunal loop with luminal occlusion.

Connexin 26 in human fetal development of the inner ear.

Specialized for intercellular communication, gap junctions have been theorized to provide a means (the epithelial and connective tissue gap junction systems) by which fluid and ions might be transported for maintenance of high levels of endolymphatic K+ [Kikuchi et al., 1994. Acta Otolaryngol. 114, 520-528] in the inner ear. A primary constituent of these gap junctions is connexin 26 (Cx26), a protein encoded by the gene GJB2 and found in both epithelial and connective tissue cells. It has been shown that a mutation in Cx26 accounts for 50% of patients with autosomal recessive nonsyndromic hearing loss. In the present study, we document the emergence and distribution features of Cx26 through various stages (weeks 11-31) of gestation in human, fetal cochleae. Comparative patterns of Cx26 distribution are also presented in the mature rat. The cochleae were fixed in 4% paraformaldehyde within 2 h post mortem. Immunohistochemical studies were performed using a rabbit polyclonal antibody raised against synthetic peptide and corresponding with amino acids 108-122. Specimens were mounted into paraffin sections. Results show that Cx26-like immunoreactivity is evident at a prenatal age of 11 weeks and maintains a high intensity of reactivity through 31 weeks of gestation. The appearance of this reactivity seemed to modulate in parallel with the onset of development and histological maturation as well as provide functional maintenance. In the human fetal cochlea, Cx26-like immunoreactivity distribution resembled adult patterns by fetal week 20. At the completion of morphological development by week 31, reactivity appeared to achieve an adult profile of distribution. Descriptions and discussion of Cx26 distribution patterns are presented in detail.

Teratoma of the umbilical cord. Case report with review of the literature.

Teratomas of the umbilical cord are very rare lesions. We found only five cases in the literature from 1887 to 1993, the latest reported in 1985. We report a case of a 10 x 7 x 5-cm mass located just at the end of an omphalocele in the umbilical cord of a full-term baby. The mass exhibited something like a cranial and a caudal pole, and tissues of all three germinal layers could be found, but there were no skeletal structures. Therefore, this lesion was diagnosed as a teratoma of the umbilical cord. We review the literature and discuss the relationship between the teratoma of the umbilical cord and the holoacardius amorphus.

DNA ploidy determination of early molar pregnancies by image analysis: comparison to histologic classification.

BACKGROUND: To improve histologic diagnosis of molar pregnancies, updated guidelines have been proposed recently. These guidelines take into account that less developed molar gestations differ from their fully developed counterparts. OBJECTIVE: To test the validity of these criteria by correlating histologic diagnosis with ploidy determination accomplished by means of image analysis. DESIGN: Fifty archival cases of early molar pregnancy were reclassified according to the new criteria. The diagnosis had to be changed from partial to complete hydatidiform mole (PM to CM, respectively) in 9 cases and from CM to PM in 4 cases. DNA image cytometry could be performed in 40 cases (CM, n = 21; PM, n = 19). RESULTS: There was 100% agreement between histologic diagnosis and a diploid or polyploid histogram in CM and 79% agreement between triploidy and PM, when the updated diagnostic criteria were used. This represents an improvement compared with diagnoses made with former criteria. Nevertheless, problems of correct classification remain: In 3 cases classified as PMs, fetal remnants were accompanied by the histologic appearance of a CM. These 3 cases could represent either a true embryonic development in CM or a twin gestation with one normal pregnancy and one mole, or they could belong to a (very rare) third type of mole. All of them show the same risk of persistent trophoblastic disease observed in classic CM. CONCLUSIONS: As the groups at risk for developing persistent trophoblastic disease can be identified by their DNA histograms, ploidy analysis would be desirable in addition to histologic examination.

Immunohistochemical and morphological studies on the human fetal cochlea: a comparative view on methods.

The preservation of morphology and antigenicity can vary uncontrollably with human fetuses since these rely heavily on immediate fixation of the temporal bone following spontaneous abortion. Once good fixation is established, there is the question of the approach taken for morphologic and immunohistochemical studies. To achieve maximal preservation for the purpose of studying normal and pathologic fetal cochleae, commonly used preparation methods for analyzing the cochlea were reviewed and compared for both immunohistochemical and morphologic studies. Cochleae obtained after spontaneous abortion ranged from the 9th gestational week to birth. Four different methods were compared for morphologic study: the block surface method; a microslicing technique; paraffin; and celloidin sectioning. For immunohistochemical study, three methods were compared: pre-embedding; paraffin; and frozen sectioning. For morphologic preservation, the block surface method gave best overall results, showing good representation of the fetal cochlea for surface preparation, light, and electron microscopy. Celloidin sectioning was also found to show good light microscopic results for both the middle and inner ear. To achieve optimal results, preservation quality, fixation procedures, and antibody all contribute to the efficacy of a methods choice.

Cerebro-oculo-facio-skeletal syndrome as a human example for accelerated cochlear nerve degeneration.

BACKGROUND: Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare autosomal-recessive disorder that includes microcephaly, severe mental retardation, and multiple congenital anomalies. Otologic findings are usually limited to descriptions of the auricles. PATIENT AND METHODS: The authors report inner ear histopathologic findings of a deceased 13-year-old patient with COFS. A histologic study of the inner ear in COFS syndrome has not yet been described. This patient was documented as having a profound bilateral sensorineural hearing loss at the age of 2 years. RESULTS: Histologic evaluation revealed accelerated neural and neuronal degeneration at the cochlear and retrocochlear levels. Remaining myelinated nerve fibers, counted in the spiral lamina, had degenerated by up to 97% when compared with normal innervation densities. Afferent nerve fibers innervating inner hair cells were completely absent, whereas medial efferent fibers to outer hair cells were found. Vestibular nerve fibers were less affected. CONCLUSION: The authors report inner ear findings that differ from animal models of primary cochlear neural degeneration and that resemble the pattern of hereditary cochlear nerve degeneration reported in Friedreich's ataxia.

Goldenhar's syndrome: congenital hearing deficit of conductive or sensorineural origin? Temporal bone histopathologic study.

BACKGROUND: Oculoauriculovertebral dysplasia (OAVD) (Goldenhar's syndrome) is a congenital syndrome with ipsilateral deformity of the ear and face, epibulbar lipodermoids, coloboma, and vertebral anomalies. Goldenhar's anomaly has often been associated with a degree of congenital hearing deficits, almost always of a conductive origin, but a sensorineural component is also suspected in some cases, evident through malformations of the inner ear. PATIENTS AND METHODS: Both temporal bones of a 10-day-old deceased patient with oculoauriculovertebral dysplasia were examined by light microscopy. RESULTS: The ear deformities included deformity of the auricle, atresia of the external auditory canal, and malformation of the tympanic cavity and ossicles. Abnormalities of the stria vascularis and the semicircular canals were also demonstrated. Further inner ear deformities were not identified in this case. CONCLUSION: These histopathologic findings appear to confirm the conductive component of the congenital hearing deficit, but a sensorineural component could not be omitted. The ear alterations favor early developmental field defects. The causes of this condition are controversial. Recent results in genetic research pertaining to the MSX class genes permit better understanding of the variety, variability, and different degrees of severity of the anomalies described here.

The impact of jejunal transplant peristalsis on enteric flora.

The importance of phase III of the migrating myoelectric complex (MMC) for homeostasis of enteric flora is well documented. The goal of this study was to evaluate in an isogeneic rat model the effect of MMC changes on the self-purging capacity of the jejunal graft. The proximal 25% of the entire jejunoileum of Lewis rats was transplanted orthotopically. Electrodes were then fixed to the graft. Native bowel of five rats and five rats with analogue jejunal segmentation served as controls. Myoelectric recordings were carried out until day 21, when animals were killed for bacteriologic analysis of the segments analyzed myoelectrically and the of neighboring gut. MMCs were observed in all animals during all recordings. Phase III was irregular in transplants because of long-lasting periods of phase III absence alternating with phase III occurring more frequently. The variation coefficient of phase III periodicity calculated for grafts was 48.74, for native bowel 14.79, and for segmented jejunum 22.9. Enteric flora found in all specimens consisted of colonic-like microorganisms. Titers of microorganisms in grafts did not differ from control segments. These findings show that phase III periodicity is severely altered in jejunal grafts. Homeostasis of enteric flora, however, is not influenced by the transplant procedure.

Necrotizing sialometaplasia in two patients with bulimia and chronic vomiting.

The purpose of this report was to present two unusual cases of necrotizing sialometaplasia of the hard palate, in which the patients were suffering from bulimia and chronic self-induced vomiting. It emphasizes the importance of confirming the diagnosis by incisional biopsy and discusses local mucosal trauma as a possible etiologic factor.

Topographic variations in anatomical structures of the anterior neck of children: an ultrasonographic study.

OBJECTIVE: Tracheostomies in children are frequently used for temporary airway support during surgical procedures. In pediatric patients with congenital craniofacial malformations, preoperative assessment of the delicate anatomy of the airway is necessary. The purpose of this study was to assess the ultrasonographic anatomy of the anterior neck with regard to the performance of tracheostomy. STUDY DESIGN: Ultrasonographic investigation was done in 50 pediatric patients (age range, 6 to 15 years) to analyze the relationships among the anatomical structures that are of practical interest with respect to tracheostomy. RESULTS: The data reveal that information concerning variations in anatomical structures lying in the immediate vicinity of the tracheostomy site was readily obtainable with the techniques used. CONCLUSIONS: In pediatric patients requiring tracheostomy for surgical treatment of severe congenital craniofacial malformations, preoperative ultrasonography may be used to diagnose individual anatomical variations at the tracheostomy site.

Idiopathic maxillary pain: prevalence of maxillary sinus hyperreactivity in relation to allergy, chronic mucosal inflammation, and eosinophilia.

OBJECTIVE: In patients with chronic orofacial pain, an underlying sinus hyperreactivity may contribute to the clinical symptoms of a diagnosis of atypical odontalgia, trigeminal neuralgia, or temporomandibular disorders. The purpose of this study was to assess the prevalence of histamine-related maxillary sinus hyperreactivity in patients manifesting signs and symptoms of idiopathic maxillary pain and to correlate the respective findings with the presence or absence of chronic maxillary sinusitis-related diagnoses such as allergy, chronic mucosal inflammation, and eosinophilia. STUDY DESIGN: Fifty patients who had been assigned a diagnosis of idiopathic maxillary pain underwent skin allergy tests, maxillary sinus histamine provocation tests, and maxillary sinus mucosa biopsy. Histamine challenge to a selected area was performed during transoral sinuscopy of the maxillary sinus; a positive test result was defined as the development of a significant local mucosa response such as reddening and swelling. RESULTS: Comparison of the data showed most patients (38%) to have an absence of chronic maxillary sinusitis-related diagnoses, whereas the most common multiple diagnosis was found to be chronic mucosal inflammation in combination with eosinophilia (22%). Regarding the prevalence rates of positive histamine provocation test outcomes, a significant difference was found between the diagnostic subgroup "absence of chronic maxillary sinusitis-related diagnoses" (36.9%) and the diagnostic subgroups "chronic mucosal inflammation" (20%; P< .05), "chronic mucosal inflammation in combination with eosinophilia" (18.2%; P< .05), and "chronic mucosal inflammation in combination with eosinophilia and allergy" (14.3%; P < .01). An analysis of the distribution of chronic maxillary sinusitis-related diagnoses revealed absence of chronic mucosal inflammation-related diagnoses to be significantly more frequently associated with positive histamine provocation test outcomes than with negative histamine provocation test outcomes (41.2% vs 19.7%; P< .01), whereas chronic maxillary sinusitis (41.0% vs 29.4%), eosinophilia (26.2% vs 17.6%), and allergy (13.1% vs 11.8%) were found to be more prevalent in patients with negative histamine provocation test outcomes. CONCLUSIONS: The findings of this study suggest patients with idiopathic maxillary pain to be associated with a low rate of sinus hyperreactivity, whereas a positive test outcome with histamine provocation may not be linked to the presence of chronic maxillary sinusitis-related diagnoses such as allergy, chronic mucosal inflammation, and eosinophilia. Further investigations using a larger sample size of patients with idiopathic maxillary pain and nonidiopathic maxillary pain are necessary to demonstrate the presence or absence of an idiopathic maxillary pain-specific prevalence of maxillary sinus hyperreactivity.

[Epidemiology of autopsy verified infection]. / Epidemiologie der autoptisch verifizierten Sepsis.

In a retrospective study of 35,220 autopsies performed from 1950 to 1984 in our department, septicaemia was found in 707 cases (2% of all autopsies). The incidence of pyaemia decreased after 1960, whereas that of septicaemia increased significantly. This increase was observed in surgical and medical departments due to patients suffering from neoplastic disease who died of septicaemia (40% of our cases). In the paediatric departments, however, mortality from septicaemia decreased slowly, but continuously. Age distribution revealed two peaks, one in infancy and one in patients older than 60 years. Over the past decade the mean age increased significantly (15 years on average). In blood cultures gram negative bacteria were found more often than gram positive strains.