Biomedical subjects

R Paniagua

Publications and source records attributed to R Paniagua.

At least 19 recordsLinked to original sources

PubMed1992

The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study.

The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti-actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti-vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin-containing cells increase.

Actins↗

PubMed1992

Macro-orchidism: light and electron microscopic study of four cases.

A hormonal and quantitative light microscopy study of one man with macro-orchidism associated with mental retardation and fragile X chromosome (case no. 1) and three men with idiopathic macro-orchidism (cases no. 2 to 4) is reported. Hormonal study revealed slightly increased follicle-stimulating hormone serum levels in cases no. 1 to 3. The testes from cases no. 1 (orchidoepididymoectomy specimen) and 2 (testicular biopsy) presented interstitial edema and three different tubular patterns that were arranged in a mosaic-like manner. Type I tubules had an increased diameter (less than 220 microns), dilated lumen, and thin seminiferous epithelium usually consisting of Sertoli cells, spermatogonia, primary spermatocytes, and sometimes a few spermatids. Type II tubules had a normal diameter (180 to 220 microns) and germ cell development varied between complete spermatogenesis and Sertoli-cell-only tubules. Type III tubules had decreased diameter (less than 180 microns), atrophic seminiferous epithelium, and thickened tunica propria. The appearance of the nuclei of the Sertoli cells in the three types of tubules could be either mature or immature. Some of the mature Sertoli cells presented a granular cytoplasm. A few of these granular cells grouped together, forming nests that protruded into the tubular lumen. The testicular biopsies from cases no. 3 and 4 only presented type II tubules that contained both mature and immature Sertoli cells. Quantitative study revealed that the large testicular size was principally due to an increased tubular length in all four cases. Although the seminiferous tubule lesions and interstitial edema suggest an obstructive process, the testicular excretory ducts (studied in case no. 1) appeared normal or only slightly dilated. It is possible that the seminiferous tubule lesions (dilated lumen and germ cell depletion) might be secondary to the Sertoli cell lesions (granular cytoplasm and nuclear immature-like pattern.

Adolescent↗

PubMed1992

Effects of cocaine on testicular structure in the rat.

The effects of hourly injections of moderate doses of cocaine hydrochloride (0.5 and 10 mg/kg body weight) over 5 h on testicular structure and testosterone levels were studied in male Wistar rats. Cocaine produced a rapid disruption of spermatogenesis; the number of normal seminiferous tubules declined to 50% (low dose) and 40% (high dose), and regressive tubules (tubules with cellular degeneration, cell sloughing, or abnormal cell structures) increased to 50% (low dose) and 60% (high dose) after treatment with cocaine. The mean tubular diameter, the surface occupied by the tubules, and the volume of seminiferous tubules per pair of testes were significantly reduced (P less than 0.01) after both doses of cocaine. Cocaine produced ultrastructural changes in the cells of the seminiferous epithelium (spermatogonia, spermatids, and Sertoli cells) including vacuoles, abundant lipid droplets, and giant mitochondria. Lower doses of cocaine increased serum testosterone levels (P less than 0.025) while higher doses did not. These findings indicate an acute effect of cocaine on the structure of the rat testis.

Animals↗

PubMed1992

Testicular fibroma.

A testicular fibroma in a 67-year-old man is reported. The tumor presented with expansive growth and myxoid areas. Atypias were absent. Differential diagnosis was made with immunohistochemical techniques that are useful for the diagnosis of nonspecialized gonadal stromal tumors. The origin of the tumor was probably in the interstitial or peritubular myofibroblasts.

Aged↗

PubMed1992

The peritubular myoid cells in the testes from men with varicocele: an ultrastructural, immunohistochemical and quantitative study.

Ultrastructural and some immunophenotypic features of the peritubular myoid cells of testes from normal men and from men with varicocele were studied. The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In normal testes only type a and b tubules were found, whereas the testes from men with varicocele showed type b-e tubules. Myoid cells in tubule types a and b showed slender cytoplasmic projections with abundant, parallel arranged microfilament bundles and electron-dense bodies. In c tubules, the myoid cells showed the same ultrastructure. The myoid cells of tubules with advanced (type d) or complete (type e) sclerosis showed irregularly outlined nuclei, scant microfilament bundles and absence of electron-dense bodies. Immunostaining of myoid cells with anti-actin antibodies was intense in types a-c tubules and scant in types d and e. Immunostaining with anti-desmin antibodies was intense in tubules types a-d, but the immunoreactive cells in types c and d tubules were irregularly shaped and distributed and were scanty in tubule type e. Immunostaining with anti-vimentin antibodies was weak in types a-c tubules and intense in types d and e tubules. Quantitative studies revealed that, with the progression of sclerosis, the numbers of both actin- and desmin-immunoreactive cells per cross-sectioned tubule, and the surface area occupied by the immunostained portion of these cells, decreases while the number of vimentin-immunoreactive cells and their immunostained surface area increases.

Adult↗

PubMed1992

Impaired atrial natriuretic factor systemic clearance contributes to its higher levels in uremia.

To evaluate the interaction between plasma levels and the systemic uptake of atrial natriuretic factor (ANF) with thyroid hormone levels during acute renal failure (ARF), seven groups of rats were analyzed: Group 1, Controls (C); Group 2, ARF; Group 3, filtering kidney with uremia; Group 4, ARF with thyroxine (T4) supplement (ARF + T4); Group 5, thyroidectomy (Tx); Group 6, ARF on Tx rats (Tx + ARF); Group 7, Tx + ARF supplemented with T4 (Tx + ARF + T4). Plasma creatinine (Cr), urea, T4, blood volume, and ANF were measured; ANF half-life (ANF t1/2; expressed in seconds) was calculated. Rats with ARF developed uremia (Cr, 377 +/- 58 versus 41 +/- 5 mumol/L), significant reduction in T4 (40 +/- 4 versus 89.2 +/- 6 nmol/L). elevation of ANF (287.7 +/- 35 versus 60.9 +/- 8 fmol/mL), and lengthening of ANF t1/2 (69.7 +/- 8 versus 37.2 +/- 6 s) compared with C (P less than 0.01). T4 supplements to ARF rats resulted in a lesser degree of uremia (Cr, 283 +/- 27; P less than 0.05) and normalization of ANF t1/2 (31.4 +/- 5); however, ANF levels remained higher than C (100.4 +/- 11.4 versus 60.9 +/- 8; P less than 0.01). Tx by itself did not change either parameter. The filtering kidney with uremia group developed mild uremia (Cr, 199 +/- 8), T4 fell (58 +/- 8), ANF levels rose (83.4 +/- 5.4), and ANF t1/2 was prolonged (54.5 +/- 12). Tx before ARF doubled the ANF level and lengthened ANF t1/2 similarly than in ARF. T4 addition (Tx + ARF + T4) normalized ANF t1/2 (29.8 +/- 3) in spite of a persistently high ANF (145.7 +/- 21). Blood volume did not change in any group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Characterisation of secondary spermatocytes in the marbled newt (Triturus marmoratus).

Secondary spermatocytes in the marbled newt (Triturus marmoratus) were identified by means of cytophotometric quantification of nuclear DNA in the testicular lobules containing primary spermatocytes in advanced stages of the first meiotic division (from pachytene onwards) and newly formed spermatids. The nucleus of secondary spermatocytes has an intermediate size between that of primary spermatocytes and round spermatids and was characterised by the presence of abundant masses of dense chromatin and the absence of a nucleolus. At the prophase the chromatin masses were located at the periphery of the nucleus. The ultrastructural study revealed that the nuclear envelope displayed blebs and that the cytoplasm was very similar to that of primary spermatocytes including the presence of smooth endoplasmic reticulum whorls, multiple small dictyosomes, and a proacrosomal-like granule near the nucleus. This granule stained weakly with aqueous PTA and was observed in about 6% of secondary spermatocytes. Many of the mitochondria were grouped beneath the plasma membrane. Approximately 2% of these cells presented an axoneme which was not associated with other flagellar components.

Animals↗

PubMed1992

The ampulla of the ductus deferens in man: morphological and ultrastructural aspects.

In order to compare the histology of the ampulla of the ductus deferens with that of the other segments of the duct in man, the seminal vesicle and the adjacent 13-15 cm of the ductus deferens were obtained during cystectomy from 15 adult men, and were processed for light and electron microscopy. Each ductus deferens specimen was divided into 3 segments: segment A or initial segment (the most proximal to the testis) showing a smooth outer surface and, on section, a uniform lumen and absence of mucosal invaginations; segment B (1.5-4 cm) showing a smooth outer surface and, on section, small cavities in the mucosa; and segment C or ampulla (3-4 cm), which was easily recognisable because of the cerebriform pattern on its outer surface. Segment A showed the usual histological pattern reported in studies of the human ductus deferens. Segment B consisted of mucosa, muscularis mucosae, submucosa, muscular coat and adventitia. The epithelial lining formed multiple branched invaginations in the lamina propria and submucosa giving rise to glandular structures. The lumen of the duct and the glands were lined by the same cell types: (1) basal cells; (2) mitochondrion-rich cells; and (3) columnar cells with the ultrastructural features of glycoprotein-secreting cells. The latter cells could be classified into 3 subtypes suggesting different stages of development: (a) with abundant mitochondria; (b) with abundant rough endoplasmic reticulum; and (c) with abundant secretory granules. Segment C or the ampulla showed the same histology as segment B except for the presence of many diverticula in the ampulla.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Bilateral mucinous cystadenocarcinoma of the testis and epididymis.

We describe an intratesticular mucinous cystadenocarcinoma in a 59-year-old man. The tumor was bilateral and appeared in the right testis and the left epididymis. The testicular tumor was a well-demarcated nodule, 3.5 cm in diameter, that extended from the lower testicular pole (close to the albuginea) to the epididymis compressing the corpus and infiltrating the cauda. The contralateral tumor, a 2.5-cm nodule located in the corpus epididymidis, compressed the ductus epididymidis. Both tumors consisted of multiple cavities varying in size, separated from one another by connective tissue septa that were incompletely lined by a columnar pseudostratified epithelium. The epithelial cells immunostained positively for carcinoembryonal antigen and comprised two cell types: cells showing a hyperchromatic nucleus, located in the basal portion of the cell, abundant rough endoplasmic reticulum, apical vacuoles, and numerous microvilli; and mucous cells. The cystic lumen showed a mucous content and sloughed epithelial cells. The differential diagnosis and histogenesis of these tumors is discussed.

Cystadenocarcinoma↗

PubMed1992

Testicular granulosa cell tumor of the adult type.

A testicular granulosa cell tumor of the adult type was studied in a 61-year-old man with a history of diabetes and urinary bladder carcinoma. The tumor was composed of three areas, each with a distinctive histologic pattern: solid, cystic, and cordlike. Most of the tumor cells in the three patterns had a round to ovoid euchromatic nucleus with one or two large nucleoli and scanty cytoplasmic organelles, mainly mitochondria and rough endoplasmic reticulum. These cells showed slight immunopositivity for vimentin and no immunostaining for cytokeratins. Occasionally, elongated nuclei displaying membrane infoldings were observed. Pleomorphic nuclei were rare. The number of mitotic figures was low. Differential aspects of testicular and ovarian granulosa cell tumors are discussed.

Granulosa Cell Tumor↗

PubMed1992

Primary testicular lesions in the twisted testis.

OBJECTIVE: To investigate primary lesions in twisted testes. DESIGN: The histologic study of testicular specimens obtained from men who had suffered testicular torsion. SETTING: The conditions required for material selection were the knowledge of the exact time of torsion and the presence of recognizable seminiferous epithelium cells. PATIENTS: Two hundred eighteen testicular torsions treated in La Paz Hospital, Madrid, Spain, from 1970 to 1990. MAIN OUTCOME MEASURES: After rejection of specimens that did not fulfill the conditions for selection, 109 biopsy and orchidectomy specimens from pubertal and adult males were studied to determine if primary lesions are superimposed to lesions secondary to anoxia. RESULTS: The following primary tubular lesions were found: (1) focal hypospermatogenesis (5 biopsies and 1 orchidectomy specimen; these testes showed degree I, II, or III anoxic lesions); (2) hypoplastic zones with only immature and hyperplastic Sertoli cells (3 orchidectomy specimens with degree III lesions); (3) zones of Sertoli-cell-only tubules that only contained a normal amount of mature appearing Sertoli cells (5 orchidectomy specimens with degree III lesions); and (4) intratubular calcifications (1 orchidectomy specimen with degree III lesions). In two cases with degree III lesions, more than one primary testicular lesion could be observed. CONCLUSIONS: An important number of twisted testes bear primary lesions that might had been involved in torsion development. The real percentage is probably even higher than that found in this study (14%) because the material obtained (biopsies) in many cases was insufficient to ensure complete exploration and because primary lesions are not recognizable in areas with pronounced anoxic lesions.

Adolescent↗

PubMed1991

Apical mitochondria-rich cells in the human epididymis: an ultrastructural, enzymohistochemical, and immunohistochemical study.

An ultrastructural, enzymohistochemical, and immunohistochemical study of the ductus epididymis in normal men was undertaken to investigate the characteristics of the apical mitochondria-rich cells (AMRCs). These cells, which differ morphologically from the principal cells (PCs), appear in isolation in the caput epididymidis (5.8 +/- 1.7 cells per cross-sectional duct) and only occasionally in the corpus epididymidis. The morphologic appearance of AMRCs varies from slender cells extending from the basement membrane to the lumen to apical cells without apparent contact with the basement membrane. The former display a round pale nucleus located in the middle of the epithelium; the apical cells have a dark nucleus, which, surrounded by a narrow cytoplasmic band, protrudes into the lumen. The cytoplasm of AMRCs is electron-dense and contains numerous mitochondria surrounded by rough endoplasmic reticulum cisternae. In the apical portion, there are lysosomes, vesicles with an electron-dense granule, and vacuoles showing a variable size and content. The stereocilia are shorter and less numerous than those of the PCs. The AMRCs are similar to the PCs in the intensely positive reaction for the enzymatic activity acid phosphatase, as well as in the lack of reaction for alkaline phosphatase and phosphorylase activities. AMRCs differ from PCs in: (1) a more intense reaction to the enzymatic activities ATPase, NADP, and succinic dehydrogenease, (2) a more intense immunostaining by AE1/AE3 and Ks4.62 anti-cytokeratin antibodies, and anti-estradiol receptor protein (D5) antibodies, and (3) a lower staining affinity for epithelial membrane antigen (EMA) antibodies. No positive immunostaining for the anti-cytokeratin Ks8.6 antibodies was observed in either AMRCs or PCs.

Adenosine Triphosphatases↗

PubMed1991

Ultrastructure of the aging human testis.

The ultrastructure of the progressive testicular involution with advancing age in men is reviewed. There is no definite age at which testicular involution begins, and the onset and severity of testicular lesions are subjected to pronounced individual variations. Hormone studies also indicate great individual variations, and subtle changes in both the testis and the pituitary develop progressively with age. Testicular size, sperm quality, and numbers of all germ cell types, Sertoli cells, and Leydig cells decrease with age. The volume occupied by the seminiferous tubules decreases, whereas that occupied by the testicular interstitium remains constant. The most frequent histological pattern of the aging testis is a mosaic of different seminiferous tubule lesions, varying from tubules with complete, although reduced, spermatogenesis, to completely sclerosed tubules. The tubules with complete spermatogenesis may show numerous morphological abnormalities in the germ cells, including multinucleation. Abnormal germ cells degenerate causing Sertoli cell vacuolation. These vacuoles correspond to dilations of the extracellular spaces resulting from the premature exfoliation of germ cells. Degenerating cells that are phagocytosed by the Sertoli cells give rise to an accumulation of lipid droplets in the Sertoli cell cytoplasm. The loss of germ cells begins with the spermatids, but progressively affects the earlier germ cell types, and tubules with maturation arrest at the level of the spermatocytes or spermatogonia are observed. The Sertoli cells show morphological abnormalities such as dedifferentiation, mitochondrial metaplasia, and multinucleation. Germ cell loss is associated with thickening of the tunica propria. When all seminiferous epithelial cells have disappeared, only an intensely collagenized tunica propria with myoid cells remains (sclerosed tubules). The Leydig cells progressively dedifferentiate with a decrease in the quantity of both smooth endoplasmic reticulum and mitochondria, together with an accumulation of lipid droplets, crystalline inclusions, and residual bodies, and formation of multinucleate cells. The development of tubular involution with age is similar to that observed after experimental ischemia, suggesting that vascular lesions may play an important role in age-related testicular atrophy.

Aging↗

PubMed1991

Immunohistochemical and quantitative study of interstitial and intratubular Leydig cells in normal men, cryptorchidism, and Klinefelter's syndrome.

Testicular specimens from normal men and men with cryptorchidism (CR) or Klinefelter's syndrome (KS) were taken, processed for light microscopy, and stained with the avidin-biotin peroxidase complex method for immunohistochemical detection of testosterone. The Leydig cells were classified by their morphology (normal, multivacuolated, and pleomorphic Leydig cells) and by their staining affinity for anti-testosterone antibodies (T-, T+, and T++ cells), and the average numbers of each cell type for each group of testes were calculated. Normal testes showed morphologically normal interstitial Leydig cells (96.0 +/- 10 per cent) and multivacuolated Leydig cells (4.0 +/- 1 per cent). Cryptorchid testes showed normal Leydig cells (85.8 +/- 11 per cent) and multivacuolated Leydig cells (14.2 +/- 2.3 per cent). Men with KS showed normal Leydig cells (78.9 +/- 9.1 per cent), multivacuolated Leydig cells (9.2 +/- 1.2 per cent), and pleomorphic Leydig cells (11.0 +/- 1.8 per cent). The percentage of T++ cells was higher in normal testes (29.4 +/- 2.1 per cent) than in CR (11.4 +/- 2.2 per cent) and KS testes (6.3 +/- 0.7 per cent). This suggests reduced functional Leydig cell activity in CR and KS. Multivacuolated Leydig cells showed weaker immunostaining than did normal Leydig cells in all the testicular groups. No immunostaining was shown by pleomorphic Leydig cells. Intratubular Leydig cells were only found in CR and KS. Immunostaining was weaker in intratubular Leydig cells than in interstitial Leydig cells. This suggests that intratubular location reduces functional activity of Leydig cells.

Adolescent↗

PubMed1991

Granular transformation of Sertoli cells in testicular disorders.

In order to study the granular transformation of Sertoli cells the following testicular specimens were reviewed: 58 postmortem biopsies from 21 children and 37 young adult males with normal histologic pattern; 165 biopsies from prepubertal cryptorchid testes; 38 biopsies and 18 surgical specimens from postpubertal-cryptorchid testes; bilateral biopsies from eight men with Del Castillo's syndrome, 14 men with retractile testes, and five men with obstructive azospermia; 17 bilateral and seven unilateral biopsies from 24 men with varicocele; seven unilateral biopsies plus five surgical specimens from 12 men with male pseudohermaphroditism; one biopsy and one surgical specimen from two men with macroorchidism; and the autopsy specimens from 28 adult men with acquired immunodeficiency syndrome (AIDS). Sertoli cells with eosinophilic granular cytoplasm were found in the testes of one prepubertal and four postpubertal cryptorchid males, two males with Del Castillo's syndrome, two males with retractile testes, four males with varicocele, two male pseudohermaphrodites, two males with macroorchidism, and one male with AIDS and interstitial orchitis. Histochemical and ultrastructural examination of granular Sertoli cells revealed that these cells accumulate secondary lysosomes and show scant cytoplasmic organelles. In the males with varicocele or retractile testes, these lysosomes were probably heterolysosomes that had degraded the germ cells and testicular fluid accumulated in the lumen of the ectatic seminiferous tubules of these testes. A similar mechanism is also probable in the male with interstitial orchitis that had caused germ cell destruction. In the other cases, in which the tubules showed reduced lumen and severe germ cell depletion, the abundant lysosomes are probably cytolysosomes. The development of these cytolysosomes might be related to the Sertoli cell dysgenesis present in these testes.

Adult↗

PubMed1990

The cycle of follicular and interstitial cells (Leydig cells) in the testis of the marbled newt, Triturus marmoratus (Caudata, Salamandridae).

Ultrastructural examination of the marbled newt (Triturus marmoratus) testis throughout the annual cycle revealed that during the period of testicular quiescence (November-February), primordial germ cells proliferate within cords of filament-rich epithelial cells that will become follicular cells (FCs). Fibroblast-like cells surround the FCs and form the lobule-boundary interstitial cells (ICs). During the period of germ cell development from primordial germ cells to round spermatids (March-June), the FCs surrounding the developing germ cells contain scanty cytoplasm with abundant rough endoplasmic reticulum and scarce filaments. With spermatid elongation (July-August), the FC size grows, its nucleus becomes irregularly outlined, and its cytoplasm displays abundant smooth endoplasmic reticulum, residual bodies, lipid droplets, and large vacuoles. After spermatozoon release by the FCs (August-September), the adjacent ICs increase their size and transform into Leydig cells with abundant smooth endoplasmic reticulum, mitochondria with tubular cristae, and lipid droplets. During the period of testicular quiescence (November-February), the Leydig cells undergo involution, eventually developing the morphological attributes of mesenchymal cells. Intermingled among these cells, cords of filament-rich cells are observed. During this period of the cycle, spermatozoon cysts supported by FCs are present. At the beginning of the germ cell proliferation period (March), these spermatozoa are released, and the adjacent ICs undergo a transformation into Leydig cells similar to those observed in August-September. Maturation and involution of ICs occur when testosterone levels are known to be rising and falling, respectively.

Animals↗

PubMed1990

Congenital testicular lymphangiectasis in children with otherwise normal testes.

Two cases of testicular lymphangiectasis are reported, occurring in stillborns. The disease is a congenital malformation consisting of an abnormal expansive development of lymphatic vessels in both testes. Autopsy study revealed the absence of pulmonary, intestinal or systemic lymphangiectasis. The testes showed normal tubular development with normal germ cell numbers and also normal Leydig cell numbers. The epididymis and spermatic cord appeared normal. In contrast with the two previously reported cases of testicular lymphangiectasis, the present cases were not associated with cryptorchidism or other malformations.

Humans↗

PubMed1990

Sertoli cell types in the Sertoli-cell-only syndrome: relationships between Sertoli cell morphology and aetiology.

Histological study of testicular biopsies from infertile men showing Sertoli-cell-only tubules due to hypogonadotropic hypogonadism, cryptorchidism, oestrogen treatment, chemotherapy or Del Castillo's syndrome, revealed four types of Sertoli cells: (1) normal adult mature cells showing an indented nucleus, grossly triangular in shape with a prominent tripartite nucleolus; (2) immature cells with round regularly outlined nuclei and immature cytoplasm; (3) dysgenetic cells showing immature nuclei and a nearly mature cytoplasm with less developed cytoplasmic organelles; and (4) involuting cells with very irregularly outlined nuclei and a mature cytoplasm containing abundant lipid droplets and residual bodies and atypical inter-Sertoli junctional specializations. Testes from men with hypogonadotropic hypogonadism showed only immature Sertoli cells; cryptorchid testes showed dysgenetic cells and occasional normal cells; and after treatment with oestrogens or chemotherapy the testes showed involuting cells and normal cells. The testes of men with Del Castillo's syndrome could be classified into three groups, according to the Sertoli cell type present: mature, dysgenetic and involuting cells. This finding suggests that Del Castillo's syndrome may be due to at least three different aetiologies.

Adult↗