Prostate-induced orgasms: A concise review illustrated with a highly relevant case study.

Current medical literature does not describe precisely the activation and mechanisms of prostate orgasms. This brief review describes what we know about the anatomy and physiology of the prostate and its involvement in reproduction and especially its stimulation for sexual recreation. It is illustrated with a highly relevant case history. Clin. Anat. 31:81-85, 2018. © 2017 Wiley Periodicals, Inc.

The effects of hypothyroidism and fasting on electrogenic amino acid transfer: possible evidence for multiple neutral amino acid carrier systems in rat jejunum.

The jejunal mechanisms for the electrogenic transfer of four neutral amino acids (alanine, leucine, methionine, valine) and for sarcosine were characterised by an electrical method in vitro. The values for apparent Km obtained electrically agree well with those assessed by conventional chemical techniques. Hypothyroidism and/or fasting rats for 3 days induced differential changes in the apparent Km and p.d.max for the various amino acids. These alterations were interpreted as indicating the presence of at least three mechanisms for neutral amino acid transfer and one for sarcosine. In euthyroid rats, only alanine showed changes in apparent Km (decrease) and p.d.max (decrease) after fasting for 3 days. With hypothyroidism the kinetic parameters of electrogenic transfer for alanine, valine and sarcosine were significantly altered while those for leucine and methionine were unaffected.

Digestion and absorption of carbohydrates--from molecules and membranes to humans.

Hydrolysis in the luminal bulk fluid by secreted enzymes is the major pathway for the breakdown of polysaccharides to oligosaccharides, and further hydrolysis is accomplished by a battery of carbohydrates in the brush border of the mature enterocytes. The glucose, galactose, and fructose produced are absorbed across the enterocytes of the upper half of the villus. Glucose and galactose (and other glucalogues) are actively transported into the enterocyte by the Na(+)-glucose cotransporter SGLT1 (gene on chromosome 22) via the transmembrane electrochemical Na+ gradient, and exit across the basolateral membrane by the glucose transporter GLUT2 (gene on chromosome 3). The critical importance of the correct expression of SGLT1 for human sugar absorption is shown by the rare genetic disease of glucose-galactose malabsorption. People with this disease cannot absorb hexoses and have severe watery diarrhea, which, if untreated, is terminal. Fructose absorption is by an Na(+)-independent transport system that has not been fully characterized (possibly GLUT5). Despite many kinetic and other studies in animals, and some in humans, that suggest multiple Na(+)-glucose transporters, only SGLT1 is expressed in enterocytes. Absorption of monosaccharides from disaccharides appears to have a kinetic advantage (disaccharide-related transport system). Hexose absorption is enhanced by dietary intake of hexoses by increased activity of SGLT1 and GLUT2 and by increased enterocyte numbers.

Regulation of human head and neck squamous cell carcinoma growth in tissue culture by opioid growth factor.

Squamous cell carcinoma of the head and neck (SCCHN) is the sixth most common malignancy worldwide. Approximately half of the patients afflicted die within 5 years of diagnosis, and surviving patients may be left with severe esthetic and functional compromise. In this study, we discovered that an endogenous opioid peptide, [Met5]-enkephalin, inhibited the growth of human SCCHN in vitro; in view of this pentapeptide's action it has been termed opioid growth factor (OGF). OGF was found to be a constitutively expressed, receptor-mediated growth inhibitory agent that appears to be autocrine produced and secreted. Growth regulation was dose-related, reversible, cytostatic, and independent of serum. All 6 human SCCHN cell lines examined exhibited growth modulation by OGF. Blockade of peptide-receptor interaction by opioid antagonists (naltrexone), or addition of antibody to OGF, resulted in substantial increases in cell number compared to control levels, showing the tonic nature of OGF-zeta activity. Immunocytochemical studies detected both OGF and its related receptor, zeta, in these cells, correlating with earlier findings of peptide and receptor in specimens of SCCHN obtained at surgery. These data suggest that a native opioid peptide, OGF, interacts with a novel opioid receptor, zeta, to tonically arrest the growth of human SCCHN.

Opioid growth factor regulates the cell cycle of human neoplasias.

The native opioid growth factor (OGF), [Met5]-enkephalin, is a tonic inhibitory peptide that modulates cell proliferation and migration, as well as tissue organization, during development, cancer, homeostatic cellular renewal, wound healing, and angiogenesis. OGF action is mediated by the OGF receptor (OGFr). To investigate the target of OGF as to cell proliferation, the effects of excess OGF, and a deprivation of OGF-OGFr interaction by an opioid antagonist, naltrexone (NTX), were examined in 3 human cancer cell lines: pancreatic (BxPC-3), colon (HT-29), and head and neck (CAL-27). OGF exposure decreased growth, DNA synthesis, and mitosis, and increased the doubling time from control levels. FACS analysis revealed a marked increase in cells in the G0/G1 phase and compensatory reduction in cells in S and G2/M phases. Consistent with this observation, the percentage of labeled mitosis (PLM) analysis showed a notable increase in the time of the G0/G1 phase. Receptor blockade with NTX increased the rate of growth, length of DNA synthesis and mitotic phases, and decreased doubling time from control values. FACS analysis indicated an increase in the proportion of cells in S and G2/M phases, and a decrease in the number of cells in the G0/G1 phase. PLM evaluation demonstrated a shortening of the length of the S and G2 phases in the 3 cell lines, and decreases in the M and G0/G1 phases in some cancers. These results indicate that OGF action is directed at the G0/G1 phase, but interruption of OGF-OGFr interfacing has widespread repercussions on the cell cycle. The data on blockade of OGF-OGFr during log phase growth suggest a requisite escorting of the growth peptide and its receptor through the cell cycle.

A journey through two lumens!

This account describes studies from the Institute of Medical Physiology in the University of Copenhagen, starting in the mid 1970's, which included some of the earliest European laboratory investigations on human female genital function. The measurements involved vaginal pH, pO2, blood flow, motility, fluid and its ionic concentrations, amino-acid concentrations and electrical activity (transvaginal potential difference) usually in both the basal and sexual aroused states. The blood flow monitoring pioneered the use of the heated oxygen electrode. Other studies examined the effects of arousal to orgasm on cervical secretion, on the heart rate as an objective indicator of orgasmic excitement and investigated the actions of TRH and the cholinergic antagonist atropine on a number of vaginal parameters. The work was part of the scientific watershed that divided the previous descriptive era of human genital mechanisms from the now prevalent quantitative assessments.

Sex and the human female reproductive tract--what really happens during and after coitus.

The scientific study of the interaction of human genitals during coitus and after ejaculation with and without female orgasm has always been difficult and controversial with ethical, technical and social problems. The present brief review examines critically the results from these studies. Early observations utilised changes induced in sexually self-aroused subjects or by coitus with artificial (transparent) penes with few objective measurements. These culminated in the synthesis of the useful unitary descriptive, EPOR (excitation, plateau, orgasm, resolution)-model by Masters and Johnson (1966). Later investigations by other workers developed or employed instrumentation to record objectively the changes induced in the motility and pressures of genital muscles, in genital blood flow, in the ion and fluid movements creating the neurogenic transudate of vaginal lubrication, in its pH and pO2 and in the disposition of the ordered spurting ejaculate with subsequent sperm transport. More recently, studies have begun to use endoscopy and ultrasound imaging to picture what really happens especially during penile thrusting. While the newer techniques have often confirmed selected features of the original EPOR model they have also shown that the characterisation of the coital changes just by a unitary model is inappropriate. New observations suggest a plurality in the changes that can occur. Coital mechanisms are dynamic and our investigations and descriptions of them should match their dynamism. The knowledge gained will be more than helpful in the treatment of infertility, genital dysfunctions and disease transmission.

Academic medical centers and the care of underserved populations.

As the number of Americans at risk of being underserved continues to rise, a better understanding of safety-net providers of health care is needed to help ensure continuing care for the underserved. In this article, the authors have begun the process of defining the role of academic medical centers (AMCs) as a group in the care of those persons most at risk of being underserved--the medically indigent and members of minority and poor populations--by quantifying the amount of inpatient care that AMCs provide to these individuals. The study went beyond previous work by using nationally representative sources of data (from 1989 to 1994) and by examining more than one underserved population rather than only the medically indigent. The study focused on AMCs and other hospitals in urban areas and excluded hospitals in rural areas. The detailed findings confirm previous observations that urban AMCs of all types provide a large and disproportionate share of care for the medically indigent and the underserved members of minority and poor populations and that members of these populations constituted the majority of patients cared for in many AMCs in recent years. The findings show that the proportion of patients from underserved groups admitted to all urban hospitals is rising and that this growth is faster among AMCs than other hospitals. The authors comment that AMCs, because of their prominent and historical role in caring for the underserved, have the opportunity to lead efforts to continue such service through innovative approaches to health care and the prevention of illness. Whether AMCs can seize this opportunity when confronted by price competition and government policies that reduce AMCs' capacity to care for the underserved remains to be seen.

The volume and mix of inpatient services provided by academic medical centers.

This is the first in a series of AAMC Papers that analyze the clinical spectrum of patients treated in the nation's teaching hospitals. As stated in the separate Introduction, "The Transformation of Data into Knowledge," subsequent papers will examine trends in the provision of care to the indigent and make comparisons of quality of care among teaching and non-teaching hospitals. These analyses, carried out by the AAMC's Center for the Assessment and Management of Change in Academic Medicine (CAMCAM), are made possible by a reorganization of the AAMC's information infrastructure, in which many formerly separate databases have been linked. The Introduction concludes with a description of specific AAMC-CAMCAM initiatives that are being planned. This initial analysis examines the volume and mix of clinical services provided by AMCs, examines trends in these services over time, and compares services provided at different AMCs, in different markets, and between AMCs and non-teaching hospitals. Data from a variety of sources were used in these secondary analyses. The American Hospital Association's Annual Survey of Hospitals database was used to analyze volumes of inpatient services provided in AMCs and other hospitals. The AAMC's Clinical-Administrative Data Service database was used to analyze the volume and mix of clinical services provided in individual AMCs. The Agency for Health Care Policy and Research's Nationwide Inpatient Sample was used to compare the mix of clinical services provided in AMCs and other hospitals. Volumes of inpatient services in AMCs changed little between 1991 and 1994 and totaled six million hospitalizations, 41 million inpatient days, and two million inpatient surgeries in 1994. The mix of inpatient services in AMCs also showed little variation over time among individual AMCs, in markets with both high and low managed care penetrations, between public and private AMCs, or between AMCs and non-teaching hospitals, with the ten most frequent diagnoses accounting for significant proportions of total services. In contrast, several specialized services were much more likely to be offered and provided by AMCs. Despite rapid change in the health care environment, the volume and mix of clinical services provided by AMCs have been relatively stable. Implications for hospital planners, service chiefs and administrators, medical educators, clinical investigators, and health policymakers are discussed.

The opioid growth factor receptor in human head and neck squamous cell carcinoma.

Carcinoma of the head and neck is the sixth leading cause of cancer in the world, and the third most common neoplasia in developing countries. More than 90% of head and neck cancers are squamous cell carcinomas (SCCHN). Approximately half of the patients afflicted die within 5 years of diagnosis and survival rates for cancer of the upper aero-digestive tract have not changed in 25 years. The opioid growth factor (OGF), ¿Met5-enkephalin, inhibits the growth of SCCHN in vitro and in vivo, and acts in a receptor-mediated fashion. Receptor binding assays using CAL-27 human SCCHN cells in culture and ¿3H-¿Met5-enkephalin were employed to identify and characterize the receptor responsible for the growth-regulatory effects of OGF. Specific and saturable binding was recorded, and Scatchard analysis showed that the data were consistent for a single binding site with a binding affinity (Kd) of 5.0+/-0.9 nM and maximal binding capacity (Bmax) of 47.5+/-1.7 fmol/mg protein. Subcellular fractionation studies determined that the optimal binding occurred with the nuclear fraction. Competition experiments demonstrated that cold ¿Met5-enkephalin was at least 7-fold greater than ligands selective for classical opioid receptors. Binding was detected in 4 other SCCHN cell lines. Receptor number in xenografts of CAL-27 was decreased almost 5-fold compared to the same cells grown in vitro. Binding to radiolabeled ¿Met5-enkephalin was recorded in SCCHN obtained from surgical resections. The function, pharmacological and biochemical characteristics, distribution and subcellular location of OGF binding in human SCCHN were consonant with the OGF receptor (OGFr).

Effect of feed interval and feed type on splanchnic haemodynamics.

AIM: To study the effect of enteral feeding on splanchnic blood flow velocity in preterm infants. METHOD: Coeliac axis and superior mesenteric artery (SMA) blood flow velocity were measured longitudinally in a cohort of 61 babies using Doppler ultrasound. RESULTS: Babies fed 1 hourly had significantly higher preprandial SMA peak systolic velocity (PSV) than those fed 3 hourly (70 vs 53 cm/s). Those fed 1 hourly showed no postprandial change whereas those fed 3 hourly showed significant postprandial hyperaemia. This hyperaemia had longer latency (42 vs 27 mins) and smaller amplitude (31 vs 25 mins) after expressed breast milk compared with preterm formula. The addition of long chain polyunsaturated fatty acids to the formulas had no effect on the postprandial response. CONCLUSION: Hourly bolus feeding leads to a persistent hyperaemic state in the SMA. The composition of feeds is an important determinant of the postprandial response of the SMA to 3 hourly feeding.

Effect of caffeine on neonatal splanchnic blood flow.

Doppler ultrasound was used to study the effect of the first intravenous dose of caffeine on splanchnic haemodynamics in preterm neonates. Peak systolic velocity in the superior measenteric artery and coeliac axis was significantly reduced for 6 hours after caffeine infusion. The effect of this reduction in blood flow to the neonatal gut is not known.

Expression of the opioid growth factor, [Met5]-enkephalin, and the zeta opioid receptor in head and neck squamous cell carcinoma.

Despite the prevalence of cancers of the head and neck, survival rates have not changed in the past few decades. Recent work has implicated peptide growth factors and their receptors in the genesis and progression of head and neck squamous cell carcinoma. Opioid growth factor (OGF, [Met5]-enkephalin) is a tonically active, autocrine and/or paracrine produced, inhibitory factor that influences the growth of normal and abnormal cells and tissues. This peptide interacts with the zeta (zeta) opioid receptor to modulate cellular proliferation, migration, and survival. Both OGF and the zeta receptor are present in mammalian tongue epithelium and skin, and modulate DNA synthesis. In the present study we examined the presence and distribution of OGF and the zeta opioid receptor in the head and neck squamous cell carcinomas from seven individuals. All specimens expressed this growth factor and its receptor regardless of tumor stage, location, and histologic grade. Immunoreactivity for both OGF and the zeta receptor were associated with the cytoplasm but not the nucleus in cells of each of these carcinomas. Our findings that a potent negative growth regulator and its receptor are present in head and neck squamous cell carcinoma lead us to suggest that OGF may modulate the growth of these types of cancers.

Aggressive papillary tumors of the temporal bone: an immunohistochemical analysis in tissue culture.

Aggressive papillary tumors of the temporal bone are neoplasms that are locally invasive and destructive. Previously classified on histologic study as middle ear adenomas or adenocarcinomas, observational evidence suggested that they arose from endolymphatic sac. To evaluate this hypothesis, we established a tissue culture from cells derived from such a papillary tumor and compared immunohistochemical stains of the original tumor with stains on endolymphatic epithelium. Similarities in expression of neuroectodermal antigens were observed. Similar staining antigens in cells derived from tumor and the endolymphatic sac provide evidence that epithelium from endolymphatic sac is the site of origin for these aggressive neoplasms. In tissue culture the cells remain contact inhibited and dependent on serum or growth factors with survival beyond the expected senescence at 30 to 50 generations. Therefore the cell culture technique provides a model for study of the disruption of growth control and invasive properties of this tumor.

Plating techniques and plate orientation in repair of mandibular angle fractures: an in vitro study.

A biomechanical model utilizing polystyrene mandibles was devised to evaluate the fixation efficacy of various plating techniques for repair of mandibular angle fractures. A simple angle fracture was created in the mandible models at a standardized location and was repaired using five different plating techniques. Each experimental group consisted of 15 mandibles, with fracture site, plate placement, load application, and fracture displacement measurement standardized to ensure consistency among experimental groups. Measurement of fracture distraction under load application generated a load deformation curve and corresponding slope for each technique. Comparison of load deformation slopes allowed assessment of fixation stability. When applied with a subapical, medially placed monocortical tension band, bicortical compression plating demonstrated the most stable fracture fixation. The data show that biplanar plate placement in both monocortical noncompression and bicortical compression techniques yields a stronger fixation than monoplanar placement.

Neuroectodermal antigens persist in benign and malignant salivary gland tumor cultures.

OBJECTIVE: To determine whether a heterogeneous collection of salivary gland tumors shared common antigenic characteristics and growth patterns in tissue culture. DESIGN: Cell cultures were derived from benign and malignant salivary gland neoplasms, cultured conservatively, and serially analyzed for epithelial, myoepithelial, and neuroectodermal antigens. SUBJECTS: Nineteen samples reflecting the spectrum of salivary tumor pathologic characteristics were established in tissue culture. Most were derived from benign pleomorphic adenomas, and several were from carcinomas, including carcinoma ex pleomorphic adenoma, and mucoepidermoid and adenoid cystic carcinoma. RESULTS: All cultures were epithelial as determined by morphologic and antigenic examination, using antibodies for cytokeratin. The phenotype of cells derived from benign tumors, especially the pleomorphic adenomas, resembled those in the original neoplasm. Those from carcinomas were similar, with less differentiated characteristics. Manipulation of growth conditions altered the phenotypes shown in culture. Some cultures contained cells expressing vascular smooth-muscle actin and glial fibrillary acidic protein or nestin. CONCLUSIONS: This model cell system containing proliferative cells from several tumor types is consistent with a stem-cell theory of salivary gland tumor origin. Our data were not consistent with the bicellular or multicellular theory. We hypothesize a neuroectodermal origin for this group of apparently heterogeneous tumors. These cultured cells will be valuable for in-depth investigation of the loss of proliferation controls in benign and malignant tumors of the salivary gland.

Cholinergic modulation of electrogenic ion transport in different regions of the rat small intestine.

Acetylcholine acting via muscarinic receptors located in the intestinal mucosa controls ion and fluid transport. This study examined the pathway(s) by which cholinergic receptors mediate secretion in rat isolated duodenum, jejunum and ileum using the short-circuit current (Isc) as an index of electrogenic CL- secretion. Carbachol and bethanechol induced electrogenic CL- transport which was insensitive to the neural blocker tetrodotoxin, indicating their direct action on the enterocytes. Functional characterization of electrogenic secretion activated via muscarinic receptors on jejunal and ileal enterocytes was achieved by use of selective muscarinic antagonists in the presence of tetrodotoxin. In both regions the rank order of potency of these compounds (atropine > 4-diphenylacetoxy-N-piperidine methiodide (4-DAMP) > hexahydro-sila-difenidol (HHSiD) > pirenzepine > methoctramine) indicated the M3 receptor subtype. Secretion activated by the muscarinic agonist 4-[[(3-chlorophenyl)amino]carbonyl]-N,N, N-trimethyl-2-butyn-1-ammonium chloride (McN-A-343) was sensitive to tetrodotoxin and pirenzepine but not to the ganglionic blocker, hexamethonium, indicating the M1 receptor subtype on post ganglionic neurons. Regional differences for bethanechol-activated secretion showed an increasing gradient in secretory capacity (Isc max) in a proximal-to-distal direction along the small intestine. Responses to McN-A-343 also showed regional differences but these were unlike those of bethanechol. These results show that cholinomimetic-induced electrogenic CL- secretion in rat isolated small intestine appears to be mediated by two dissimilar populations of muscarinic receptor: M3 muscarinic receptors positioned on enterocytes and M1 muscarinic receptors sited on submucosal neurons.

Human immunodeficiency virus--associated non-Hodgkin's lymphoma presenting as an auricular perichondritis.

AIDS-related NHL is an aggressive neoplasm, usually of high or intermediate grade, frequently extranodal at initial treatment, and often the first manifestation of AIDS. Although complete remissions have been reported, they occur in only a minority of patients. We describe a patient with NHL of the external ear that masqueraded as an auricular perichondritis. This is the first case reported in which AIDS-related NHL first appeared in the ear, and this should alert physicians who treat patient with AIDS to be aware of the protean manifestations of this disease.

Hybrid tumors or salivary gland tumors sharing common differentiation pathways? Reexamining adenoid cystic and epithelial-myoepithelial carcinomas.

Three adenoid cystic carcinomas and two epithelial-myoepithelial carcinomas, which focally shared common histologic features, were studied to examine the common differentiation pathways manifested by these tumors and to discuss criteria for hybrid salivary gland tumors. Regions of the adenoid cystic carcinomas had cellular features ranging from simple clear cell change of basal/myoepithelial cells to combined clear cells and prominent ductal structures mimicking epithelial-myoepithelial carcinoma. Conversely, two epithelial-myoepithelial carcinomas had adenoid cystic carcinoma-like regions caused by the formation of "pseudocysts"; this resulted in a focal cribriform pattern. Electron microscopy of two additional but typical epithelial-myoepithelial carcinomas revealed both excess basal lamina at the margins of cellular nests and widened intercellular spaces containing reduplicated basal lamina and accumulations of glycosaminoglycans; these ultrastructural features were identical to those seen in adenoid cystic carcinomas. The five current cases are not examples of hybrid tumors, but they demonstrate the effects of gene expression and the resulting differentiation of synthetic products and tumor cells that are generally restricted to one or the other of these two tumor types by as-yet-unknown means. To avoid misdiagnosis and its prognostic implications, adenoid cystic carcinoma-like regions in epithelial-myoepithelial carcinoma and epithelial-myoepithelial-like regions in adenoid cystic carcinoma should be recognized simply as anomalous differentiation.