Complete Atrophy Research Articles

Increased laminin deposition in capillaries of the stria vascularis of quiet-aged gerbils

The distribution of laminin (LA) and type IV collagen (IV-C) in the gerbil inner ear was investigated by light and electron microscopic immunohistochemistry. Changes in protein expression were assessed from birth to old age to determine the relation of these constituents to maturation of the cochlea and development of presbyacusis. The distribution of LA paralleled that of IV-C during postnatal development, and both were visualized in the basement membrane (BM) of endothelial, epithelial and spiral ganglion cells in neonatal and young adult gerbils. Immunopositive BM underlying the stria vascularis disappeared at 8–12 days after birth coincident with the development and maturation of the strial capillaries. Immunoreactivity for LA afforded an index to the thickness of the BM and was found to increase with age only in the BM of strial capillaries. At 6 months of age, occasional strial capillaries in the apex of the cochlea showed thickening of the LA-positive BM. Abnormal deposition of LA in strial capillary BM spread to lower turns and increased in prevalence with advancing age, affecting apical and basal more than middle cochlear turns. Thickening of the capillary BM appeared to precede capillary obstruction which eventuated in complete strial atrophy. Staining for IV-C in the walls of the strial capillaries did not increase with age. The data show that LA and IV-C play important roles in postnatal development of the cochlea and that LA deposition increases with age only in the BM of strial capillaries.

The photoperiodic response in Syrian hamsters depends upon a melatonin-driven rhythm of sensitivity to melatonin.

The pineal gland conveys photoperiodic information to the brain through its daily pattern of melatonin (MEL) secretion. The duration of MEL secretion is proportional to the duration of the night. To determine the mechanism by which MEL transduces photoperiod, we used a protocol of daily MEL infusion given to sexually active pinealectomized Syrian hamsters. A long MEL signal (10 h) inhibited sexual activity, whereas a 5-hour infusion had no effect. However, animals given a 2.5-hour infusion twice separated by an interval of 3 h produced complete gonadal atrophy. Changes in the time interval between infusions blocked the potency of the MEL infusion, suggesting a tight temporal relationship between MEL signals. Additionally, the infusions were as effective whether applied during the day or during the night, in both long and short photoperiods. These data suggest that there is a rhythm of sensitivity to MEL involved in the photoperiodic response which is entrained by MEL itself.

Optic neuropathy following simulation of orbital hemorrhage in the nonhuman primate.

The goal of the study was to determine, using a nonhuman primate (NHP) model, the minimum duration of elevated intraocular pressure (IOP) (induced by an inflated catheter) necessary to produce significant visual system deficits. In Old World monkeys (Macaca mulatta), a catheter was placed retrobulbarly in one orbit and inflated with saline for either 180 min (10 monkeys) or 240 min (six monkeys subjects). Baseline color fundus photographs, monochromatic photography, fluorescein angiography, and IOP measurements were performed preoperatively and at either 2, 4, or 6 weeks postoperatively on both eyes of each monkey prior to killing and histological analysis. Optic neuropathy was demonstrated in eight of these NHPs. In the two most severe cases (240 min inflation condition), complete nerve fiber atrophy with central retinal artery occlusion was observed. Sector nerve fiber atrophy, extending from the temporal disc to beyond the macula, was noted in the other six monkeys, five of which were in the 180 min inflation condition. Thus, optic neuropathy, sufficient to produce visual loss, was noted following increased IOP (> or = 50 mm Hg) for 180 min or 240 min. These data emphasize the need for timely intervention to mitigate the potential detrimental effects of retrobulbar hemorrhage when it occurs in humans.

Histological Findings in Cryptorchidism

Cryptorchidism is an anomaly in the migration of the testis. Although frequent (1% of the population), the causes are still not fully clear. The associated histological lesions are constant and are worse the longer the testis remains in an anomalous position and the higher this position. Alterations in the maturation of the germinal cells appear very early at about the 7th month of life, gradually becoming more severe until there is complete atrophy of the seminiferous tubules in post-puberty. With histological lesions in the cryptorchid testis there is a risk of seminomatous cancer developing in the undescended testis and of a mixed or non-seminomatous type in the descended testis. Orchiopexy does not reduce the risk of cancer in the cryptorchid testis, but it does eliminate the hyperthermic state in the gonad and allows a simpler, more reliable clinical and biopsy assessment of the testis after surgery.

The Photoperiodic Response in Syrian Hamster Depends upon a Melatonin‐Driven Circadian Rhythm of Sensitivity to Melatonin

The pineal gland, via the daily pattern of melatonin (MEL) secretion, is directly involved in the conduction of photoperiodic information. The duration of MEL secretion is proportional to the duration of the dark period and, whatever the photoperiod is, MEL synthesis occurs 3 or 4 h after the dark onset in Syrian hamsters. In order to determine the relative importance of the duration or the coincidence hypothesis, a daily infusion protocol was used in sexually active pinealectomized hamsters. Long duration of MEL infusion (10 h) completely inhibit testes whereas short duration infusion (5 h) had no effect. When the animals were infused twice within 2 h 30 min separated by 3 h, they presented a complete gonadal atrophy, similar to the one observed with the 10 h infusion. Measurement of plasma MEL during the infusion and separation periods revealed that MEL reached physiological nighttime values during the infusion period and fell to daytime values 1 h after the end of an infusion period. Thus, the results could not be due to a time additive action of the two MEL pulses. An intermediate response was observed when the 2 signals were applied across the light/dark transition. Gonadal regression did not occur when the 2 periods of infusion were separated by 5 h 30 min. The efficiency of this type of infusion was not dependent on the ambiant photoperiod since similar results were obtained in long and short photoperiods. The infusion was also as effective during the day as well as during the night. These results suggest that there is a rhythm of sensitivity to MEL, based on the coincidence hypotheses, that are important for transmission of photoperiodic information. This rhythm of sensitivity to MEL seems to be entrained by MEL itself, since the efficiency of the two pulses of MEL is not dependent of time of application and/or of photoperiod.

Evaluation of Adaptive Changes by Non-Invasive Imaging in Hepatic Vein Outflow Obstruction

Hepatic vein outflow obstruction induces remarkable changes of intra–hepatic blood circulation; the significance of these changes remains uncertain. Six patients with obstruction of the hepatic veins were evaluated by duplex Doppler ultrasound and computed tomography. The adaptive changes secondary to obstruction were analyzed and their significance was correlated with the clinical findings. Four patients presenting unilateral hepatic vein occlusion had unilateral reversed portal flow. Two of them, with lobar liver atrophy and contralateral compensatory hypertrophy required operation; the other two, with normal appearance of the liver, benefitted from conservative treatment. Two patients with bilateral hepatic vein occlusion, intra-hepatic bypasses, bilateral lobar atrophy and caudate lobe hypertrophy, received operations. Intrahepatic unilateral portal flow reversal compensates for unilateral hepatic outflow obstruction. The combination of complete or subtotal hepatic vein obstruction and atrophy–hypertrophy complex predicates advanced disease despite flow reversal or spontaneous shunt.

Are the annual reproductive and body weight rhythms in the male European hamster (Cricetus cricetus) dependent upon a photoperiodically entrained circannual clock?

Most of the data obtained so far on the European hamster (Cricetus cricetus) suggest direct photoperiodically driven seasonal changes in sexual activity and body weight. The results of the present long-term study support the hypothesis that these annual changes are the expression of photoperiodically driven endogenous circannual rhythms. When subjected following capture (April-May) to constant conditions of long photoperiod (LP) and constant temperature a large number of the European hamsters present, in September-December, complete gonadal atrophy associated with a decrease in body weight. A sexual reactivation as well as an increase in body weight are observed in the same animals between January and April. Of the six animals that survived long enough, two only presented partial gonadal atrophy during the second year. These observations clearly demonstrate that the decline in sexual activity in subjective autumn does not require a decrease in photoperiod, at least in the first year. Theoretically, the observed rhythms, if circannual in nature, would be generated by a self-sustained annual oscillator (circannual clock) able to function in the absence of a photoperiodic input. Pinealectomy makes animals unable to detect or measure photoperiodic information. Of the six European hamsters tested (pinealectomized in June and then kept continuously under LP), five showed clear annual rhythms in body weight and reproductive capacities for two consecutive years. Clearly endogenous annual rhythms were expressed in these conditions. To be entrained to a 1-year period, such a circannual clock should, however, be able to react to either LP and/or to short-photoperiod (SP), at least at certain periods of the annual cycle. In animals exposed to LP in August or October, after gonadal atrophy had been established by exposure to natural SP, gonadal regrowth started in December or January, about 2 to 3 months earlier than in animals kept outside or in experimental SP. With the same experimental conditions, exactly the same results were obtained in pinealectomized animals; thus stimulatory effect of LP or LP-induced phase advance of the circannual clock can be excluded. The absence of the SP information would then induce such reaction. In animals kept under constant LP and temperature following capture, however, pinealectomy in January--when all animals are sexually active--induces gonadal atrophy within--weeks. This clearly demonstrates that LP is stimulatory at this time of the subjective year.

Childhood progressive spinal muscular atrophy with facioscapulo-humeral predominance, sensory and autonomic involvement and optic atrophy

A female child of healthy parents developed rotary nystagmus at the age of 15 months. Ophthalmoscopy disclosed incomplete optic atrophy. Blood tests, EEG and CT scans were normal. At 20 months progressive muscular weakness and wasting with limb-girdle distribution commenced, followed later by disturbance of gait. From muscle and nerve biopsy the diagnosis of a peripheral neuropathy with neurogenic muscular atrophy was made. No mental change occurred. At 23 months she sustained cardiac arrest and was resuscitated; thereafter, she remained in a vegetative state and expired 9 months later. Her brain was markedly atrophic and firm. Diffuse old ischemic necroses and neuronal loss with gliosis were found in the cortex, the neostriatum, the thalamus, parts of the lower brainstem, and the cerebellum. Her optic nerves and tracts showed complete atrophy. The spinal cord exhibited degeneration and loss of motor neurons with crevical accentuation. The intermediolateral nuclei, the dorsal nuclei and the spinal ganglia were also involved. There was demyelination of the posterior funiculi, the pyramidal tracts, and the sciatic, peroneal, sural, and superior frontal nerve. The voluntary muscles exhibited large group atrophy with liposclerotic change and limb-girdle predominance. The neck, tongue and ocular muscles were also involved, as were, to a less extent, the lower limbs. Although the loss of motor neurons in the spinal cord and at the bulbar level with the typical pattern of neurogenic muscular atrophy, as well as its distribution, resemble the facioscapulo-humeral type of hereditary motor neuropathy (HMN), early onset, rapid course, sensory and autonomic involvement, and atrophy of the optic nerve do not fit this or any one type of HMN.

Is contralateral exploration necessary in infants with unilateral inguinal hernia?

Between 1973 and 1985, 165 infants (aged 1 week to 6 months) underwent unilateral inguinal herniotomy at our hospital. An attempt was made to trace these 165 children. It proved possible to contract and examine 116 children (104 boys and 12 girls). Age at follow-up ranged from 5 to 17 years. Parents were asked whether their children had attended any hospital for the treatment of contralateral hernia. All children were examined for the evidence of contralateral hernia. Boys were also examined for the position and size of the testis. Testicular volume was assessed with the help of Prader's Orchidometer. Twelve children (10.3%), 11 boys and 1 girl, subsequently developed contralateral inguinal hernia. The mean time interval between initial hernia operation and subsequent development of contralateral hernia was 164 days (range, 7 days to 18 months). Diminished size of testes was observed on the side of the operation in six patients and one patient had complete testicular atrophy. Three boys had a testis in the groin, presumably hitched up at operation and all three required orchidopexy. In view of the relatively low incidence of contralateral hernia and increased risk of damage to testes, we feel that routine contralateral exploration is not justified.

Macular Pigment Epitheliopathy in Retinopathy of Prematurity-Reply

In Reply. —For some time, physicians have been intrigued concerning the ophthalmoscopic phenomenon of retinal pigment epithelium abnormality associated with regressed ROP. 1 This abnormality is manifest by varying degrees of loss or increase of pigmentation of the pigmented epithelium, may appear in any subretinal location, and may sometimes involve complete atrophy of the choroid. Dr Hindle, in his letter, claims precedent for the name macular pigment epitheliopathy , assigned by him in publications as early as 1982, to such alterations. His assertions to this effect and supporting references that also posit causes speak for themselves. The pathogenesis of such phenomena and their effects on visual function remain incompletely understood. Our data confirm this. Our choice of nomenclature, retinal pigment epithelial scarring , is taken from the classification employed in the macular photographic scoring protocol used in the CRYO-ROP study, 2 which in turn is based on the International Classification of ROP

Ophthalmological study of the lesions induced by the filarial worm with dermal microfilariae, Monanema martini, in its murid hosts.

The filaria Monanema martini with skin-dwelling microfilariae induces in its natural murid hosts lesions similar to those in human onchocerciasis. This was demonstrated by histo-pathological studies but it appeared useful to evaluate the model by a clinical investigation. An ophthalmological analysis was performed on the two species of hosts, inoculated by one, two, or multiple doses of larvae, and with infections of at least one year duration. A total of 140 eyes was examined (anterior and posterior segments). We established a system for enumerating the different types and severities of lesions. We prepared a file for each eye and attempted to quantify our observations. The significant lesions were different in the two host species. In Arvicanthis niloticus, in which motile microfilariae were seen in the anterior segment, punctate keratitis was predominant. In Lemniscomys striatus, the posterior segment showed complete chorioretinal atrophy, similar to the final stage of onchocercal chorioretinitis in humans. M. martini represents in its natural hosts two complementary models for the study of the pathogenesis and treatment of human onchocerciasis.

Interaction between serotonin and a dopamine precursor (given 8 hour apart) and luteinizing hormone alters reproductive and metabolic responses of migratory red headed bunting(Emberiza bruniceps)

Abstract During the progressive phase of the seasonal breeding cycle four groups of male buntings were treated with (i) Normal saline (control), (ii) Luteinizing hormone (LH), (iii) L‐Dihydroxyphenylalanine (L‐DOPA, a dopamine precursor) given 8 hr after 5‐Hydroxytryptophan (5‐HTP, serotonin) (8‐hr relationship) and (iv) LH and these neurotransmitter precursor drugs with the same temporal relationship (LH + 8 hr). The results indicate that at the end of the study, while the controls as well as the LH treated birds exhibited full breeding condition (although its degree of development was higher in the latter), the testes of birds of the “8‐hr group”; showed complete atrophy. But, the birds receiving both treatments (LH + 8 hr) were not different from the controls. The body weight responses of the birds followed the same pattern as those of testes weight. It is suggested that the phase relationship of serotonergic and dopaminergic drugs controls the reproductive (gonadal activity) and metabolic (body weight...

Suppression of annual testicular development in Indian Palm squirrel, Funambulus pennanti by 8 hr temporal relationship of serotonin and dopamine precursor drugs.

Daily injections of 5-HTP (5-hydroxytryptophan, serotonin precursor) and L-DOPA (L-Dihydroxyphenylalanine, dopamine precursor) given 8 hour apart inhibited normal testicular growth in seasonally breeding Indian Palm Squirrel, Funambulus pennanti leading to complete gonadal atrophy, which was maintained till the end of the study. HCG administration induced higher degree of gonadal development but, when the two treatments (HCG + 8 hr relationship of 5-HTP and L-DOPA) were given simultaneously no significant difference was observed compared to control. Results indicate that induced suppression of gonadal function in a fashion similar to seasonal regression leading to non-breeding condition is the consequence of specific phase relationship (8 hr) between serotonergic and dopaminergic activities and not due to Serotonin or dopamine alone. This suggestion gets support from the finding that gonadal condition of squirrels receiving only 5-HTP (5-HTP control) or L-DOPA (DOPA control) was not different from control and exhibited normal testicular growth. It also seems that neurotransmitter precursor drugs given 8 hr apart possibly inhibited the activity of neuroendocrine-gonadal axis since this effect was overpowered by stimulatory effect of gonadotrophin. The findings strongly support the hypothesis that specific phase relation of circadian serotonergic and dopaminergic oscillations account for seasonal reproductive conditions.

Atrophie villositaire associée à une hypoparathyroïdie idiopathique corrigée par la 1 alpha-hydroxyvitamine D 3 et le calcium

We record the case of a 82 years old woman with an idiopathic hypoparathyroïdism (calcemia: 1,28 mmol/l; PTHi: 5,7 pg/ml) associated to a complete villous atrophy. Restitutio ad integrum of the intestinal mucosa was obtained by the sole treatment of hypoparathyroïdism with calcium and 1 alpha (OH) D3.

A Case of Sjögren's Syndrome With Repeatedly Negative Findings on Lip Biopsy

We report a case of Sjögren's syndrome characterized by keratoconjunctivitis sicca, parotid swelling, reduced salivary flow, and abnormalities on nuclear scanning. Two labial gland biopsies showed complete atrophy. Biopsy of an enlarged submandibular gland revealed lymphoid follicles and glandular replacement consistent with the diagnosis of Sjögren's syndrome. This case supports the concept that a negative finding on labial biopsy does not rule out a diagnosis of Sjögren's syndrome.

Endometrial morphology after 12 months of vaginal oestriol therapy in post-menopausal women

The endometrial effect of long-term vaginal oestriol (E 3) therapy for urogenital atrophy was assessed in 23 post-menopausal women. Hysteroscopic and histological examinations were performed in each patient to assess endometrial atrophy before treatment and after 6 and 12 months of therapy (0.5 mg vaginal E 3 for 21 days, then 0.5 mg twice weekly). The primary atrophie picture was confirmed at the end of the 6th month in all but one of the patients. In one case, the histology showed an abnormal stromal reaction with no epithelial alterations. Treatment was continued and after the 12th month complete atrophy was confirmed both hysteroscopicaliy and histologically in all patients. Efficacy as regards vaginal and urogenital complaints was good. Our results demonstrate that in women with endometrial atrophy effective and well-tolerated treatment with vaginal E 3 can be safely continued for up to 12 months.

Addison's disease, hypertension, renal and hepatic microthrombosis in ‘primary’ antiphospholipid syndrome

We describe a 14 year old boy with antiphospholipid syndrome who initially presented at the age of 10 with recurrent loin pain, fever, weight loss, leucocytosis, thrombocytopenia, hypertension and haematuria. He had primary adrenal insufficiency with bilaterally enlarged adrenals on computed tomographic (CT) scan consistent with adrenal infarction. Renal and liver biopsies showed microthrombi in the glomerular capillaries and hepatic sinusoids respectively. The case is unusual in that hypertension rather than hypotension was dominant and a CT scan was consistent with bilateral adrenal infarction without haemorrhage. He represented with evidence of persistent hypertension with glomerulosclerosis and glomerular microthrombi on repeat renal biopsy. He continues to have permanent adrenal insufficiency with complete atrophy of his adrenals.

Elimination of testicular regression by 12-hr temporal relationship of serotonergic and dopaminergic activity in Indian Palm Squirrel,Funambulus pennanti

Specific temporal relationship (12-hr) of serotonin and dopamine activity was induced by precursor drugs (5-HTP and L-DOPA) in Indian Palm Squirrel Funambulus pennanti during testicular regression phase. This treatment established breeding condition unlike control, which experienced complete atrophy of testes and accessory sex organs. It is obvious that seasonal testicular regression of Indian Palm Squirrel can be eliminated by 12 hr relation of 5-HTP and L-DOPA, which is not a pharmacological effect but actually is an alteration of seasonality in this annually breeding subtropical mammal. It may be concluded that specific phase relation (12-hr) between circadian serotonergic and dopaminergic oscillations may induce breeding condition in regressing gonad of Indian Palm Squirrel during post-reproductive phase of annual gonadal cycle. It is also suggested that inspite of the different environmental factors (photoperiod, humidity etc.) used by different species to time their annual reproduction, basic regulatory mechanism of seasonality appears to be the same, i.e., temporal synergism of neurotransmitter activity.

Neuropathologic Observations in Congenital Phrenic Nerve Palsy

A right phrenic nerve palsy with severe respiratory and feeding difficulties throughout the patient's 2 1/2 years of survival was found at autopsy to relate to grossly complete atrophy of the muscle of the right diaphragm. An oblique fibrotic scar transected the right phrenic nerve at the level of the brachial plexus. There was marked reduction of the number of anterior motor neurons in the right central portion of cervical segments 2, 3, and 4. The lesion in the phrenic nerve is what would be expected following stretching during delivery.

Temporal synergism of neurotransmitter affecting drugs and seasonal reproductive responses of Indian Palm Squirrel,Funambulus pennanti

Daily injections of L-dihydroxyphenylalanine (L-DOPA, dopamine precursor) given 12 hour after 5-hydroxytryptophan (5-HTP, serotonin precursor) eliminated annual testicular regression in seasonally breeding sub-tropical Palm Squirrel that undergoes seasonal changes in responsiveness to day-length and humidity. Other temporal relations (L-DOPA given 0, 4, 8, 16 and 20 hours after 5-HTP administration) decreased/delayed the rate of regression and maintained the reproductive system at intermediate level. 12-hour-relation maintained full breeding condition (maximum gonad and accessory sex organs) unlike control, which exhibited complete atrophy of primary and accessory sex organs. It seems likely that these injections entrained the circadian serotonergic and dopaminergic oscillations and the interaction/phase relation of these two systems through their many circadian expressions (neural/hormonal) accounts for the seasonal interpretation of environmental factors. It is suggested that response in the present study is not a pharmacological effect of drugs but temporal synergism of neural activities affected the seasonality of reproduction as only 12-hour-relation of 5-HTP and L-DOPA maintained breeding activity during post reproductive phase of annual gonad cycle in Palm Squirrel.