Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

Relocation of patients after cardiac surgery: is it worth the effort?

BACKGROUND: Fast-track protocols may facilitate early patient discharge from the site of surgery through the implementation of more expedient pathways. However, costs may merely be shifted towards other parts of the health care system. We aimed to investigate the consequence of patient transfers on overall hospitalisation, follow-up and readmission rate after cardiac surgery. METHODS: A single-centre descriptive cohort study using prospectively entered registry data. The study included 4,515 patients who underwent cardiac surgery at Aarhus University Hospital during the period 1 April 2006 to 31 December 2012. Patients were grouped and analysed based on type of discharge: Directly from site of surgery or after transfer to a regional hospital. The cohort was obtained from the Western Denmark Heart Registry and matched to the Danish National Hospital Register. RESULTS: Median overall length of stay was 9 days (7.0;14.4). Transferred patients had longer length of stay, median difference of 2.0 days, p < 0.001. Time to first outpatient consultation was 41(30;58) days in transferred patients vs. 45(29;74) days, p < 0.001. 18.6% was readmitted within 30 days. Mean time to readmission was 18.4 ± 6.4 days. Median length of readmission was 3(1,6) days. There was no difference in readmissions between groups. Leading cause of readmission was cardiovascular disease with 48%. CONCLUSION: Transfer of patients does not overtly reduce health care costs, but overall LOS and time to first outpatient consultation are substantially longer in patients transferred to secondary hospitals than in patients discharged directly. Readmission rate is high during the month after surgery, but with no difference between groups.

N-terminally and C-terminally truncated forms of glucose-dependent insulinotropic polypeptide are high-affinity competitive antagonists of the human GIP receptor.

BACKGROUND AND PURPOSE: Glucose-dependent insulinotropic polypeptide (GIP) affects lipid, bone and glucose homeostasis. High-affinity ligands for the GIP receptor are needed to elucidate the physiological functions and pharmacological potential of GIP in vivo. GIP(1-30)NH2 is a naturally occurring truncation of GIP(1-42). Here, we have characterized eight N-terminal truncations of human GIP(1-30)NH2 . EXPERIMENTAL APPROACH: COS-7 cells were transiently transfected with human GIP receptors and assessed for cAMP accumulation upon ligand stimulation or competition binding with (125) I-labelled GIP(1-42), GIP(1-30)NH2 , GIP(2-30)NH2 or GIP(3-30)NH2 . KEY RESULTS: GIP(1-30)NH2 displaced (125) I-GIP(1-42) as effectively as GIP(1-42) (Ki 0.75 nM), whereas the eight truncations displayed lower affinities (Ki 2.3-347 nM) with highest affinities for GIP(3-30)NH2 and GIP(5-30)NH2 (5-30)NH2 . Only GIP(1-30)NH2 (Emax 100% of GIP(1-42)) and GIP(2-30)NH2 (Emax 20%) were agonists. GIP(2- to 9-30)NH2 displayed antagonism (IC50 12-450 nM) and Schild plot analyses identified GIP(3-30)NH2 and GIP(5-30)NH2 as competitive antagonists (Ki 15 nM). GIP(3-30) NH2 was a 26-fold more potent antagonist than GIP(3-42). Binding studies with agonist ((125) I-GIP(1-30)NH2 ), partial agonist ((125) I-GIP(2-30)NH2 ) and competitive antagonist ((125) I-GIP(3-30)NH2 ) revealed distinct receptor conformations for these three ligand classes. CONCLUSIONS AND IMPLICATIONS: The N-terminus is crucial for GIP agonist activity. Removal of the C-terminus of the endogenous GIP(3-42) creates another naturally occurring, more potent, antagonist GIP(3-30)NH2 , which like GIP(5-30)NH2 , was a high-affinity competitive antagonist. These peptides may be suitable tools for basic GIP research and future pharmacological interventions.

Species-specific action of (Pro3)GIP - a full agonist at human GIP receptors, but a partial agonist and competitive antagonist at rat and mouse GIP receptors.

BACKGROUND AND PURPOSE: Specific, high potency receptor antagonists are valuable tools when evaluating animal and human physiology. Within the glucose-dependent, insulinotropic polypeptide (GIP) system, considerable attention has been given to the presumed GIP receptor antagonist, (Pro3)GIP, and its effect in murine studies. We conducted a pharmacological analysis of this ligand including interspecies differences between the rodent and human GIP system. EXPERIMENTAL APPROACH: Transiently transfected COS-7 cells were assessed for cAMP accumulation upon ligand stimulation and assayed in competition binding using (125) I-human GIP. Using isolated perfused pancreata both from wild type and GIP receptor-deficient rodents, insulin-releasing, glucagon-releasing and somatostatin-releasing properties in response to species-specific GIP and (Pro3)GIP analogues were evaluated. KEY RESULTS: Human (Pro3)GIP is a full agonist at human GIP receptors with similar efficacy (Emax ) for cAMP production as human GIP, while both rat and mouse(Pro3)GIP were partial agonists on their corresponding receptors. Rodent GIPs are more potent and efficacious at their receptors than human GIP. In perfused pancreata in the presence of 7 mM glucose, both rodent (Pro3)GIP analogues induced modest insulin, glucagon and somatostatin secretion, corresponding to the partial agonist activities observed in cAMP production. CONCLUSIONS AND IMPLICATIONS: When evaluating new compounds, it is important to consider interspecies differences both at the receptor and ligand level. Thus, in rodent models, human GIP is a comparatively weak partial agonist. Human (Pro3)GIP was not an antagonist at human GIP receptors, so there is still a need for a potent antagonist in order to elucidate the physiology of human GIP.

Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco.

We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco.

Choristomas of the oral cavity: a review.

The choristoma is a tumorlike mass of normal cells in an abnormal location. Intraoral choristomas have been reported under a wide variety of names. This comprehensive review of the English-language literature on oral choristomas offers a classification of these lesions, analyzes their clinical and histologic features, and discusses possible pathogeneses and treatment.

Peripheral (extraosseous) calcifying odontogenic cyst. A review of forty-five cases.

The peripheral calcifying odontogenic cyst (PCOC) is a rare lesion. The number of well-documented cases reported in the English-language literature until now is 38. The purpose of the present study is twofold: (1) to report seven new cases of PCOC and (2) to review and analyze the clinical and histomorphologic features of the previously reported cases of PCOC together with those of the present study. Most of the lesions were located in the maxillary and mandibular gingiva or alveolar mucosa anterior to the region of the first molar. Histologically, 66% of the lesions were of the cystic variant and 34% of the solid (neoplastic) variant. The terminology of the lesion and its histogenesis are discussed.

Melanocytic hyperplasia of the oral mucosa.

Lesions that exhibit melanocytic hyperplasia are uncommon in the oral mucosa. They are even more rare than the various morphologic types of nevomelanocytic lesions. This article reports the clinicopathologic features of oral lesions diagnosed as lentigo simplex, junctional lentigo ("jentigo"), atypical melanocytic hyperplasia (melanoma in situ), and melanocanthoma. The proper terminology for these lesions is also discussed.

Oral focal mucinosis.

Oral focal mucinosis (OFM) is an uncommon clinicopathological entity which is considered to be the oral counterpart of cutaneous focal mucinosis and/or cutaneous myxoid cyst. It is comprised of a clinically elevated mass with a histological picture of localized areas of myxomatous connective tissue. The present study adds 15 new cases of OFM to the literature and analyzes their clinical, histological and histochemical features. Most of the lesions were located in the gingiva and alveolar mucosa. The nature of the lesion is unclear and it is suggested that the mucinous accumulation is the result of fibroblastic overproduction of hyaluronic acid.

Hyaline ring granuloma: a distinct oral entity.

Hyaline ring granuloma (HRG) is a distinct oral entity. In this study, 64 cases from the literature are analyzed and two new cases are reported. The lesions could be classified by location as central hyaline ring granuloma (42%) and peripheral hyaline ring granuloma (53%). Radiographically, a radiolucent area irregularly outlined by well-formed trabeculae of bone was found in central HRG, and a poorly defined erosion at the crest of the alveolar ridge was often found in peripheral HRG. Occasionally, the lesion occurred in the connective tissue wall of cysts (5%). The etiology of this condition is controversial, but most lesions were in edentulous areas and most patients had a history of tooth extraction or other trauma. The majority of cases (83%) occurred in the mandible, usually posterior to the premolar. The mean age of patients at diagnosis was 43 years, and the male/female ratio was 1.9:1. Pain was not a symptom, although local discomfort, such as recurrent swelling and tenderness, was noted in many cases. Hyaline rings with giant cell inclusions are the significant features for histopathologic diagnosis. HRG is treated by curettage or surgical excision, care being taken to remove the entire lesion. The removal of a peripheral HRG in an edentulous jaw should be followed by careful smoothing of the bone surface, since the lesion tends to infiltrate and is not well demarcated. Recurrence, probably due to incomplete excision, is uncommon.

A comparison of carbon dioxide laser, liquid nitrogen cryosurgery, and scalpel wounds in healing.

With the carbon dioxide surgical laser, the liquid nitrogen cryoprobe, and the scalpel, wounds were created on the shaved abdomen of 24 rats, and the patterns of healing were studied. The laser wounds were the first to epithelialize, followed by the scalpel wounds, with the cryosurgery wounds the slowest to epithelialize. The results were confirmed histologically.

Ganglioneuroma of the mandible.

This article reports a very rare case of ganglioneuroma within the mandible. The patient, 15 years of age at first diagnosis, has now had 17 years of followup and remains generally healthy, despite the continued presence of the tumor. Possible origin of the lesion, histologic differentiation of this tumor from normal ganglia, and recommendations for management are discussed. Two reported cases of ganglioneuroma that occurred centrally in the mandible are also reviewed.

Clear cell odontogenic carcinoma: report of three cases with pulmonary and lymph node metastases.

Three cases of a newly described rare odontogenic tumor are reported. One patient died with pulmonary metastases, one had an associated odontogenic cyst and one exhibited regional lymph node metastasis. The cases lend support to the odontogenic origin and metastatic capability of the clear cell odontogenic tumor. The authors recommend aggressive therapy and believe that the tumor should be considered a clear cell odontogenic carcinoma.

Mixed odontogenic tumors: an analysis of 23 new cases.

The ameloblastic fibroma, ameloblastic fibrodentinoma, and ameloblastic fibro-odontoma are mixed odontogenic tumors that are considered to arise from both epithelial and mesenchymal elements of the tooth germ. This article presents the clinical and histopathologic characteristics of 23 new cases. The patients' ages ranged from 3 to 19 years (median 9). Most tumors were asymptomatic and were associated with an unerupted tooth or teeth. All patients were treated with simple enucleation of the tumor. We found that histologically these lesions comprise a spectrum. Some were probably benign odontogenic tumors (neoplasms) and others were odontomas undergoing maturation (hamartomas); however, in any given case we were, on histologic grounds, unable to differentiate the two. The majority, if not all, of our cases were nonaggressive with little or no tendency to recur, whereas some reported cases have exhibited local aggressiveness and recurrence, suggestive of neoplasia. In our opinion, it is clinically important to distinguish the mixed odontogenic tumors from ameloblastoma since the mixed tumors, found mostly in children, are relatively benign when compared to ameloblastoma, which is found in all age groups (usually adults). The usually innocuous behavior of these lesions does not justify aggressive treatment initially, and simple enucleation should be appropriate in most cases.

Aortic regurgitation after surgical relief of subvalvular membranous stenosis. A long-term follow-up study.

A postoperative follow-up study of 21 cases of discrete membranous subvalvular aortic stenosis is presented. The age at operation was 6-47 (mean 16) years, and the follow-up time 0.6-16 (mean 6.7) years. Preoperatively most patients were in NYHA function class II or III and had high peak systolic pressure gradient, left ventricular hypertrophy and/or cardiothoracic index greater than 0.50. At follow-up all but six patients were in NYHA class I, the Doppler-estimated peak systolic gradient was 0-36 (mean 18) mmHg, the cardiothoracic index unchanged and the mean left ventricular hypertrophy score had declined from 4.3 to 2.3. Of 13 patients without aortic regurgitation preoperatively, eight had regurgitation at follow-up (group I) and five did not (group II). The interval to follow-up was significantly longer and the preoperative peak systolic gradient was greater in group I than in group II. Aortic regurgitation may develop even after surgical relief of discrete membranous subvalvular aortic stenosis, possibly associated with high preoperative pressure gradient and time from operation. Regular postoperative Doppler echocardiography is therefore recommended.

Peripheral odontogenic fibroma.

Peripheral odontogenic fibroma (WHO type) is an uncommon lesion of the gingiva; 18 well-documented cases have been published. It is considered to be the extraosseous counterpart of the central odontogenic fibroma. Because of the paucity of reported cases, the full histomorphologic spectrum of this lesion has not yet been established. This article presents nine cases of peripheral odontogenic fibroma that illustrate the variety of its histopathologic findings. The connective tissue ranged from loose (almost myxomatous) to markedly cellular to relatively acellular and well-collagenized. Islands and/or strands of odontogenic epithelium were present in all lesions. Matrix of mineralized material was present in three cases, and juxtaepithelial hyalinization was seen in one case. To avoid the introduction of additional diagnostic terms, we suggest that all these lesions be considered a spectrum of the peripheral odontogenic fibroma (WHO type). We also suggest that the term WHO type be used to distinguish peripheral odontogenic fibromas from the peripheral ossifying fibroma with which they have often been confused.

Nuclear DNA analysis of oral hyperplasia and dysplasia using image cytometry.

We investigated the value of image analysis in discriminating among oral white lesions with hyperplasia without dysplasia and oral white or white-and-red lesions with moderate or severe dysplasia. Normal oral epithelial tissue was used as a control. Image analysis was applied to 5-micron formalin-fixed sections stained with the azure A-Feulgen reaction for nuclear DNA. For 150-200 cells from each section, 5 nuclear variables were assessed: area, form factor, total stain, average stain and ellipticity. For each variable, 2 measurements were obtained, the mean and the interquartile range, and were used for stepwise discriminant analysis. Using this test, a model of 3 measurements with the most discriminating power was developed. When the jackknife classification test was applied to this model, we could discriminate with 81% accuracy between the 4 groups of tissue studied.

Central giant cell lesions of the mandible and maxilla: a clinicopathologic and cytometric study.

Computer-assisted image analysis was used to measure four histopathologic parameters (number of giant cells, mean number of nuclei per giant cell, fractional surface area, and relative size index) in two groups of patients with central giant cell lesions in a search for possible histologic predictors of clinical behavior. The lesions of 22 patients were classified clinically into nonaggressive and the lesions of 10 patients were classified into aggressive categories in accordance with the method of Chuong and Kaban. The majority of patients with aggressive lesions had recurrent tumors within 2 years and/or experienced pain, root resorption, and cortical perforation. Giant cells were selected in 25 random high-power magnification (X400) fields and measured by means of the Leitz Texture Analysis System-Plus. Linear stepwise discriminant analysis was applied to each parameter studied. Clinically aggressive giant cell lesions were characterized by a higher number of giant cells and greater fractional surface area when compared with the nonaggressive tumors. With the use of the "jackknife" classification procedure, the accuracy of the two statistically significant parameters (number of giant cells and fractional surface area) in predicting the aggressiveness or the nonaggressiveness of our group of central giant cell granulomas was, respectively, 70% and 82%. This study provides further evidence that the use of cytometric analysis of giant cells may be helpful in predicting prognosis and in planning treatment for these often difficult-to-manage lesions.

Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new cases and review of 155 cases from the literature. Part II: Analysis of 191 cases.

Review and analysis of data on 191 cases of oral pigmented nevi from the literature and from two studies at the University of California, San Francisco, revealed that nevi of the intramucosal type are the most common, followed by the common blue nevus. Compound and junctional nevi are rare, and combined nevi are the rarest. The data on location, presence of clinical pigmentation, configuration, size, and duration of the nevi, as well as on the patient's age, sex, and race, are analyzed. Blue nevi were found mostly on the hard palate, whereas intramucosal nevi occurred on the buccal mucosa, on the gingiva, and on the lips as well as on the palate. Nonpigmented nevi were especially common (22%) in the intramucosal group. Most oral nevi are raised, which can be of help in the differential diagnosis. Oral nevi are small, most being between 0.1 and 0.6 cm at the largest dimension. Because the malignant potential of oral nevi is still uncertain and because preexisting macular pigmentation is present in about one third of all patients with oral melanoma, it is advisable to accurately diagnose all oral pigmented lesions, many of which will require microscopic examination.