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Biomedical subjects

D F Cameron

Publications and source records attributed to D F Cameron.

At least 55 records · Page 3Linked to original sources

Interstitial compartment pathology and spermatogenic disruption in testes from impotent diabetic men.

Studies utilizing animal models of diabetes suggest that diabetic complications of impotence involve structural lesions in the testis as part of an overall defect in the pituitary-testicular axis. In the present study testicular biopsies from ten oligospermic and/or impotent men with diabetes were evaluated by light and electron microscopy. One biopsy was judged normal. The remaining tissue showed variable testicular pathology ranging from minimally to grossly affected. Seminiferous tubules had decreased tubule diameters, hyalinized tubule walls, and occluded lumina owing either to epithelial encroachment or cellular debris and exfoliated round germ cells. Sertoli cells were vacuolated and showed a high degree of apical cell membrane redundancy and degeneration. Although Sertoli-Sertoli cell junctional complexes appeared normal, Sertoli junctional specializations associated with spermatids were structurally abnormal or absent. All tubules were variably depleted of adluminal compartment germ cell types. The interstitial compartment was filled with a collagen-rich extracellular matrix concentrated around small blood vessels and seminiferous tubule walls. Capillaries and lymphatic endothelia appeared structurally abnormal and compromised by the interstitial "matrix expansion." Some Leydig cells contained a variable number of small to large lipid droplets, vacuoles, and secondary lysosomes. Results indicate the presence of tissue pathology in testes of impotent diabetic men. Discrete ultrastructural lesions in apical Sertoli cell cytoplasm are associated with spermatogenic disruption and morphological changes in the interstitial compartment suggest microvascular complications.

Adult↗

Gonadal dysfunction in the spontaneously diabetic BB rat: alterations of testes morphology, serum testosterone and LH.

Serum testosterone, luteinizing hormone (LH), testicular histology and ultrastructure were examined in 91 spontaneously diabetic BB, semi-starved, and control Wistar rats. Between 80-120 days of age serum testosterone was decreased (1.67 +/- .25 vs. 2.95 +/- .48 ng/ml; P less than .05) in the BB rats compared to controls but not different from semi-starved rats. LH values were similar in control and BB rats (49.4 +/- 10.9 vs. 46.8 +/- 6.2 ng/ml). Abnormal lipid droplets were noted within Leydig cells at this period. From 121-150 days of age serum testosterone was lower in BB (1.38 +/- .23 vs. 3.42 +/- .45 vs. 2.94 +/- .81 ng/ml; P less than .05) than controls or semi-starved rats. Serum LH was not significantly higher in controls than in BB rats (63.2 +/- 7.4 vs. 36.6 +/- 12 ng/ml; P = NS). Between 151-200 days of age, there was further lipid accumulation in Leydig cells in the BB rat and occasional epithelial disorganization. After 200 days, serum testosterone decreased (P less than .05) to similar levels in both control and BB rats (1.42 +/- .87 vs. 1.22 +/- .25; P = NS) and was similar in BB rats after 250 days (1.02 +/- .2 ng/ml). After 250 days of age Leydig cell morphology appeared relatively normal but marked alterations were apparent in Sertoli cells, germ cells and morphology of the tubule wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Return of gonadal function in men with prolactin-secreting pituitary tumors.

Gonadal function was evaluated in 10 men [33 +/- 17 (SD) yr] with pituitary tumors and hyperprolactinemia (47-2550 ng/ml) using nocturnal penile tumescence (NPT), semen analysis, urinary LH and FSH excretion, and diurnal variation of serum testosterone and PRL. Results were compared to 16 normal subjects (33 +/- 13 yr). NPT was decreased in tumor patients as demonstrated by reduced maximum circumference change (P less than 0.01) and total tumescence time (P less than 0.05). Semen analysis was examined in 5 patients able to produce specimens. All seminal parameters were significantly abnormal as demonstrated by oligospermia, asthenospermia, teratospermia , and elevated fructose. Urinary LH [570 +/- 72 (SE) vs. 838 +/- 22 mIU/h; P less than 0.01] and serum testosterone (235 +/- 60 vs. 625 +/- 63 ng/dl; P less than 0.01) were decreased in 9 tumor patients, all of whom had serum PRL levels above 50 ng/ml. Diurnal variation of serum PRL was absent in hyperprolactinemic patients whereas all had normal circadian changes in serum testosterone, although at a lower set point. Eight patients were followed for 6-13 months after reduction of serum PRL by surgery and/or drug therapy. Serum PRL reached normal levels in six men after 6 months of treatment. Selected individuals had an increase in serum LH after 2 months of treatment. Significant rises in serum testosterone occurred as early as 3 months and normal levels were found in six patients after 6-8 months of treatment. Only two subjects, however, demonstrated a normal semen analysis. These data suggest that men with serum PRL levels above 50 ng/ml maintain a normal diurnal pattern of serum testosterone at a lower set point, and demonstrate hypogonadism with reduced urinary LH excretion and NPT. In addition, routine seminal parameters are clearly abnormal and are both delayed and incomplete in their recovery.

Adolescent↗

Three patterns of extra-testicular venous drainage in the rabbit. Divergence from a traditional concept.

Seventy-eight male New Zealand white rabbits were autopsied and found to have variable left extra-testicular venous anatomy. Our observations reveal that in the rabbit the left testis is drained in one of three ways, identified as either A (18%), B (30%) or C (52%)--type drainage. The right testicular vein in all cases drained directly into the inferior vena cava immediately superior to the right iliolumbar vein. In type A drainage, the left testicular vein drained directly into the inferior vena cava at the level of the left iliolumbar vein. In type B drainage, the left testicular vein emptied into the left iliolumbar vein, which in turn drained into the inferior vena cava. In type C drainage both the left testicular and iliolumbar veins anastomosed to form a "lumbotesticular" trunk which emptied directly into the left renal vein. These three patterns of left venous vascular anatomy in the rabbit can be explained on the basis of their embryologic development. Our observations suggest that it is the caudal segment of the left pelvic subcardinal vein and its anastomosis with the caudal cardinal complex which persist as the left testicular vein and that the more cranial segment of this vein, heretofore presumed to remain patent, atrophies to the level of the developing left renal vein.

Animals↗

Surgical induction of varicocele in the rabbit.

Surgically induced varicoceles were created in male rabbits of proven fertility by partially occluding the left lumbotesticular trunk, which receives the left testicular vein before draining into the left renal vein. Semen was collected every 2 weeks following surgery and left testicular biopsy was performed at 2, 4, 8 and 13 postoperative weeks. Tissue was processed for light and electron microscopy. Animals were sacrificed at 20 postoperative weeks. Left testicular vein dilatation was observed at autopsy (20 weeks postoperative), as were changes in semen quality. These included an increase in the number of round germ cells and abnormal spermatozoa, as well as a decrease in sperm numeric density and motility. Seminiferous tubule pathology was variable and germ cell sloughing was observed as soon as 8 weeks following surgery. Spermatids were maloriented relative to Sertoli cells and Sertoli-germ cell junctional complexes were structurally abnormal. Results indicate that surgical induction of varicocele in the rabbit leads to altered spermatogenic function and decreased semen quality similar to that described in humans. Epithelial disruption appears to be a phenomenon of the adluminal testicular compartment and apical Sertoli cell cytoplasmic degeneration may account for the poor semen quality associated with varicocele.

Animals↗

Gonadal dysfunction in the spontaneously diabetic BB rat.

Diabetes which occurs spontaneously in the BB Wistar rat is associated with reduced fertility, predominantly in breeding males. In the first month of diabetes, there is a significant (p less than 0.05) reduction in serum testosterone associated with a transient decrease of serum LH and the accumulation of lipid in Leydig cells. Between one and three months of diabetes, there is an increase in both serum testosterone and LH and a further deposition of lipid droplets in Leydig cells. From three to six months of diabetes, there is a reduction of serum testosterone similar to age-matched controls, but high serum LH levels persist. Similar levels of LH and testosterone are noted after six months of diabetes, and all BB rats show marked changes in seminiferous tubules. These morphological changes in tubules consist of increased tubular wall thickness, severe germ-cell depletion, and Sertoli-cell vacuolization. Similar morphological changes of testes associated with generalized atrophy are noted in all control rats after 16 months of age. Decreased fertility in the BB rat appears to be associated with a primary disorder of Leydig cells, which precedes changes in seminiferous tubules consistent with accelerated aging. Preliminary data in impotent diabetic men suggest that the BB rat may be a valuable model for investigating human diabetic impotence and infertility.

Age Factors↗

Structural response of adult rat Sertoli cells to peritubular fibroblasts in vitro.

Sertoli cells were harvested from sexually mature rats and maintained in vitro for up to ten days (Sertoli cell-enriched cultures) or co-cultured with rat peritubular fibroblasts. Cultures were examined by differential light microscopy and by scanning or transmission electron microscopy. The presence of peritubular fibroblasts in co-culture greatly enhanced plating efficiency and viability of adult Sertoli cells. Sertoli cell aggregates preferentially adhered to peritubular cells, and by ten days had flattened and spread across these cells. Sertoli cells retained their characteristic ultrastructural features. Early in co-culture a collagen-like extracellular material was seen bridging Sertoli and peritubular cells, and its appearance was coincident with the presence of swollen rough endoplasmic reticulum in peritubular cells. Interperitubular cell spaces became engorged with a fibrillar material morphologically similar to the basal lamina of the seminiferous tubule wall. In the absence of peritubular cells, in culture medium "conditioned" by prior incubation with peritubular cells but not containing them, or when cultured with other fibroblastic cells, plating efficiency was low; Sertoli cells never flattened and cell ultrastructure progressively degenerated. The results indicated that peritubular cells support adult Sertoli cells in culture, possibly via extracellular material derived from peritubular cells, and suggest that Sertoli cells have an inductive effect on peritubular cell secretory activity.

Animals↗

Ultrastructural alterations in the adluminal testicular compartment in men with varicocele.

Testicular biopsies from 21 otherwise healthy men with diagnosed varicocele were processed for light and electron microscopy. Whereas germ cell morphology and tissue architecture of the basal testicular compartment appeared normal, cellular mophology and intercellular associations of the adluminal testicular compartment were variably altered. In affected tubules, spermatid nuclear and acrosomal morphology was abnormal and sloughing was evident. Spermatids were maloriented relative to Sertoli cells, and Sertoli-germ cell junctional complexes appeared to be structurally abnormal. Contradistinctly, Sertoli-Sertoli cell junctional complexes appeared unaffected. Results from this study indicate that testicular disruption in varicocele is a phenomenon of the adluminal compartment, that the Sertoli cell is, in fact, more sensitive to perturbation of the testicular environment than are germ cells, and that the Sertoli cell is the primary intratubular site of alteration leading secondarily to spermatogenic disruption.

Acrosome↗

The blood-testis barrier in men with varicocele: a lanthanum tracer study.

Testicular biopsy specimens were obtained from 28 otherwise healthy males (22 to 37 years old) with diagnosed varicocele. Tissue was processed for ultrastructural and intercellular tracer studies using lanthanum nitrate. In all cases Sertoli-Sertoli junctional complexes appeared structurally intact and functionally normal on the basis of their ability to occlude lanthanum from the adluminal testicular compartment. Our results indicate that, even in the presence of severe dissolution of the adluminal testicular compartment as evidenced in varicocele, both the basal compartment and the blood-testis barrier remain relatively normal. In varicocele, not only does the blood-testis barrier remain effective in segregating the two testicular compartments, but it appears to act as a device that limits the progression of apical Sertoli cell cytoplasmic degeneration and seminiferous epithelial dissolution, thereby allowing a pool of progenitor germ cells to be maintained and protected in the basal compartment.

Adult↗

Selection of students for admission to medical school: A two-class decision approach.

The validity coefficient alone does not communicate sufficient information to estimate the errors in decisions to accept or reject candidates. By means of probability theory, it is demonstrated how information concerning errors in decisions may be estimated. With estimates of the frequencies of correct and incorrect decisions and the costs of such decisions, a utility index was defined, for which a minimum was sought as a function of the entrance requirement. Under the analytic criterion defined for utility, it was possible to determine for a number of cost systems the entrance score which would, in the long run, reduce losses to a minimum. The application of the model is illustrated using empirical data and hypothetical cost systems. For these data entrance requirements were determined according to the criterion in addition to selection ratios and probabilities of success.

Aptitude Tests↗

The combined effects of ethanol and amphetamine sulfate on performance of human subjects.

The combined effects of ethanol and amphetamine on the performance of selected tests were evaluated. No differences were shown between the effects of ethanol-amphetamine and ethanol-lactose on the performance of balance, skipping, Minnesota manipulation, Purdue peg board, Maudsley Personality Inventory, pursuit rotor or digit span tests; but ethanol plus amphetamine produced less impairment of performance of coding, mental addition, and trail making tests than did ethanol plus a placebo. Ethanol increased the errors in performance of the Wonderlic Personnel Test, but the simultaneous administration of amphetamine did not reduce this effect. Conversely, amphetamine reduced the test-retest reliability of the Wonderlic Personnel Test, but alcohol appeared to counteract this effect of amphetamine. These experiments indicate that, when ethanol and amphetamine are used together, each drug modifies some of the effects produced by the other in a manner that cannot be predicted on the assumption that a depressant versus stimulant competition is operative.

Adult↗

Ultrastructural lesions in testes from hyperprolactinemic men.

Testicular tissue from eight men with prolactinomas and elevated serum prolactin were evaluated by light (LM) and transmission electron microscopy (TEM). A semiquantitative assessment of testicular morphology was employed to provide a morphology index for each tissue specimen. Although in each biopsy specimen germ cell exfoliation was evident, as was abnormal structural change in the seminiferous epithelium, there was no apparent correlation with the overall degree of tissue pathology (morphology index) and the serum level of prolactin. All of the tissue displayed variably thickened seminiferous tubule walls which, when viewed by TEM, were composed of thickened laminae propriae and redundant and involuted basal laminae. Likewise, all tubules contained Sertoli cells with overt cytoplasmic degeneration, principally in the apical (adluminal) region of the cell. This was visualized, in part, as a retraction of the apical cytoplasm from periluminal spermatids and degeneration or absence of Sertoli-germ cell junctional specializations. Sertoli-Sertoli cell junctional complexes appeared structurally intact. Leydig cell ultrastructure was typical of normal cells and contained a variable amount of lipid and smooth endoplasmic reticulum. This also was without positive correlation with the overall degree of tissue pathology or level of serum prolactin. Our results demonstrate the variable degree of testicular pathology associated with hyperprolactinemia in man, and suggest that abnormal tubule walls and altered Sertoli cell ultrastructure are consistent findings in this abnormal endocrine condition.

Adult↗

Alterations of testicular function induced by hyperprolactinemia in the rat.

The effects of hyperprolactinemia on testicular structure and pituitary-gonadal function were investigated in male rats. Hyperprolactinemia was induced in the Wistar-Furth rat by implantation of tissue fragments of a prolactin-secreting MtTW15 pituitary adenoma. The MtTW15 tissue was maintained in one animal group for 27 days (group A) and in another group for 37 days (group B). Appropriate age-matched controls were utilized in each study. Serum prolactin was significantly elevated (P less than 0.001) in both groups of MtTW15-bearing rats compared with their controls. The degree of hyperprolactinemia was more severe in rats of group B (2842 +/- 546 ng/ml) than in rats of group A (367 +/- 38 ng/ml). Accessory sex organ weights in group B rats were significantly lower than in controls, but were apparently unaffected in group A rats. Hyperprolactinemia induced definite but variable testicular alterations in both animal groups that presented as seminiferous epithelial disorganization, germ cell exfoliation, increased tubule wall thickness, and abnormal Leydig cell lipid content. Electron microscopy revealed structural disruption of Sertoli-germ cell junctional complexes and apical Sertoli cell cytoplasmic degeneration. The hyperprolactinemic rat exhibited significant reductions in serum luteinizing hormone (LH), testosterone (T), and androgen binding protein (ABP) when compared with controls. Eighty-six days following surgical removal of the MtTW15 tissue in a subgroup of group B rats, serum levels of prolactin and LH returned to normal, as did weights of accessory sex organs and testicular morphology. These results indicate that exposure to the MtTW15 adenoma and its later removal in the rat provides a workable model for studying the effects of hyperprolactinemia on testicular structure and function, and for identifying events involved in the subsequent recovery of spermatogenic disruption.

Adenoma↗

The pituitary-testicular axis at rest and during moderate exercise in males with diabetes mellitus and normal sexual function.

Hormonal studies of pituitary-testicular function in insulin-dependent diabetes mellitus were examined at rest and during moderate exercise to assess whether diabetes per se caused abnormalities of nocturnal penile tumescence and androgen function in men with normal sexual function. The present study compared 10 healthy men and eight men with Type I diabetes mellitus in whom normal sexual function was determined by clinical history. Urinary gonadotropin excretion, semen analysis and diurnal variation of serum glucose, prolactin, testosterone and free testosterone were determined in both groups. In addition, the serum levels of testosterone, free testosterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured at rest, during 45 minutes of exercise on a bicycle ergometer at 50% of the subjects previously determined maximal oxygen uptake (VO2 max) and during a 30-minute recovery period. Nocturnal penile tumescence and parameters of semen analysis were similar in both groups. Urinary FSH excretion and serum FSH were higher (P less than or equal to 0.01) in the diabetic subjects while urinary LH excretion was similar. Diurnal variation of serum prolactin, testosterone and free testosterone were similar in both groups. Exercise produced a significant (P less than or equal to 0.01) increase in maximal free and total testosterone in both groups without changes in serum FSH or LH. Prolactin increased significantly (P less than or equal to 0.01) during exercise in the diabetic group only. We conclude that, for the most part, the pituitary-testicular axis and nocturnal penile tumescence under basal conditions and the pituitary-testicular axis during moderate exercise are similar in healthy males and insulin-dependent diabetic males with normal sexual function.

Adolescent↗

Ultrastructural surface characteristics of seminiferous tubules from men with varicocele.

Testicular biopsies were obtained from 40 otherwise healthy men with diagnosed varicocele and processed for scanning electron microscopy. Testis biopsies from two men with scrotal pain served as control. The seminiferous epithelium was variably affected, ranging from what appeared to be essentially normal to severely altered. In tubules in which normal cellular associations were compromised, the surface anatomy of the tubule epithelium was distorted, adluminal sertoli cell cytoplasm was truncated and there was an apparent displacement, reduction in number and, in some extreme cases, absence, of germ cells. Visualization of the varicocele-affected seminiferous epithelium by the scanning electron microscope reveals more fully the extent and three-dimensional character of adluminal compartment dissolution and reconfirms our four stage classification of seminiferous tubules in this pathology.

Adult↗