Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10.

Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of these responses. The aim of this study was to determine whether cytokine gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty-six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-2 promoter region polymorphism. TNF-a, TNF-d, and IL-10 microsatellite polymorphisms were also analyzed. The frequency of the anti-inflammatory cytokine IL-10 promoter (-1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA-TT-AA homozygous genotype combination of three single-nucleotide polymorphisms at -1082, -819, and -592 in the IL-10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF-alpha, IL-6, and IL-2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL-10 genotypes with differences in IL-10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide-stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position -1082 produced lower levels of IL-10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL-10 promoter, -1082 A-positive genotype in patients with renal artery stenosis, suggests that IL-10 may protect against the development of atherosclerotic renovascular disease.

Allele frequencies for an interferon-gamma microsatellite in a population of Brazilian leprosy patients.

A group of Brazilian leprosy patients and controls were genotyped for a CA-repeat microsatellite polymorphism within the interferon (IFN)-gamma gene. A significantly higher frequency of alleles 5-7 was observed in this patient population, indicating that IFN-gamma gene polymorphism may contribute to the course of leprosy post-infection.

Allele frequencies for an interferon-y microsatellite in a population of Brazilian leprosy patients

A group of Brazilian leprosy patients and controls were genotyped for a CA-repeat microsatellite polymorphism within the interferon (IFN)-gamma gene. A significantly higher frequency of alleles 5-7 was observed in this patient population, indicating that IFN-gamma gene polymorphism may contribute to the course of leprosy post-infection.

Allele frequencies of polymorphisms of the tumour necrosis factor-alpha, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK.

Cytokine gene polymorphisms affecting cytokine production may influence rejection and graft-versus-host disease following solid organ and haemopoietic stem cell (HSC) transplantation, respectively. Polymorphisms in the regulatory regions of several cytokine genes have been described; for example, tumour necrosis factor-alpha (TNF-alpha) has a G/A substitution at position -308, interleukin-2 (IL-2) has a T/G substitution at position -330 and interleukin-10 (IL-10) has substitutions at positions -1082(G/A), -819(C/T) and -592(C/A). Microsatellites associated with cytokine production have been detected in the first intron of the IFN-gamma gene and flanking the TNF-alpha gene. In this study, we have genotyped a single panel of healthy Northern European Caucasoids living in the south-east of England for the above-mentioned polymorphisms and compared the results to those published for other populations. A PCR method using sequence-specific primers (SSP) was developed for genotyping the IL-2 polymorphism, and the ABI PRISMtrade mark 310 genetic analyser was used to detect the TNF-alpha and IFN-gamma microsatellites. The allele frequencies of all the studied polymorphisms were consistent with those reported for other UK Caucasoid populations, but differences were observed when compared to other Oriental, African and Caucasoid groups. If these cytokine polymorphisms prove to have functional consequences, then any differences across population groups may have significant clinical relevance in disease and in the outcome of solid organ and HSC transplantation.

Stress-induced oviposition delays in laying hens: duration and consequences for eggshell quality.

1. This study investigated relationships between the timing of stress, duration of oviposition delays and consequences for eggshell quality, in 2 experiments with ISA Brown hens. 2. Periods of up to 6 h of environmental stress (relocation from an individual cage to a larger one containing 3 unfamiliar hens), commencing up to 4.5 h before predicted oviposition time, reliably induced oviposition delays. Many hens still retained their egg when stress ended. 3. Ovipositions that occurred during stress were never delayed for more than 3.0 h beyond the expected time. Ovipositions that occurred after the period of stress ended usually did so after <1 h if the delay at the end of stress was less than about 2.4 h. Delays that ended either during stress or <2 h after stress ended were classified as short-term. 4. If an oviposition delay was more than about 2.4 h when stress ended, the egg concerned was usually laid much later, after a delay of 7 to 15 h. Delays that ended >5 h after stress ended were classified as long-term. 5. Eggs delayed long-term were white-banded and the subsequent egg was slab-sided, or occasionally soft-shelled. Short-term delays often caused eggshell dusting with varying amounts of superficial calcification. Hence, duration of oviposition delay affects both the number of abnormal eggshells and the degree of abnormality. 6. The present findings are of potential importance to both the egg industry and breeders, because abnormal eggshells cause downgrading and can impair embryonic development. Also, numbers of abnormal eggshells and degree of abnormality can be used as indicators of environmental stress.

Oviposition delays induced by social stress are reversed by treatment with the beta-adrenergic blocking agent propranolol.

Contact with unfamiliar conspecifics (social stress) caused hens to delay oviposition. These delays were prevented by propranolol (10 mg/kg), suggesting that beta-adrenergic receptors are involved in their physiological causation.

Morphological variation of Dalén-Fuchs nodules in sympathetic ophthalmia.

Fifty cases of sympathetic ophthalmia were examined histologically to determine the incidence and morphology of Dalén-Fuchs nodules. At least one well-defined Dalén-Fuchs nodule was identified in 18 (36%) of the eyes examined. Three types of lesions at the level of the retinal pigment epithelium were recognised. One type was found to consist of focal hyperplasia and aggregation of retinal pigment epithelial cells. A second type, classically referred to as Dalén-Fuchs nodules, consisted of epithelioid cells and lymphocytes covered by an intact dome of retinal pigment epithelium. The third type of lesion was characterised by degeneration of the overlying retinal pigment epithelium leading to disorganisation of the Dalén-Fuchs nodule and possible release of their contents into the subretinal space. Our study demonstrated that Dalén-Fuchs nodules in sympathetic ophthalmia vary in their morphological appearance as determined by light microscopy.

Cataract extraction in the sympathizing eye.

Cataract extraction was performed on the sympathizing eyes of six patients with sympathetic ophthalmia. In five patients the clinical diagnosis of sympathetic ophthalmia was supported by the results of histologic examination of the exciting eye. The postoperative period averaged 12 years, and visual acuities ranged from 20/25 to light perception. The presence of posterior synechiae posed the major complicating operative factor. Cystoid macular edema, vitreous opacity, pupillary membrane formation, and corneal opacification were associated with postoperative visual impairment in four cases. We conclude that the underlying status of the sympathizing eye at the time of cataract extraction and postoperative management are critical factors that influence ultimate visual outcome.

Effect of corticosteroid treatment and enucleation on the visual prognosis of sympathetic ophthalmia.

A retrospective clinicopathologic study, conducted to determine the course of disease in 30 cases of sympathetic ophthalmia with clinical follow-up of at least six months (average, 12.7 years), showed that 21 of 30 patients retained visual acuities of 20/50 or better in the sympathizing eye. The severity of inflammation graded histologically in the exciting eye did not correlate with the clinical course of final visual acuity in the sympathizing eye. Enucleation of the exciting eye within two weeks of the onset of symptoms was associated with a relatively benign clinical course (P = .008). Corticosteroid treatment in patients who underwent enucleation more than two weeks after the onset of symptoms was associated with a good visual outcome (P = .009). Early enucleation of a blind exciting eye and corticosteroid treatment appear to be important variables that influence the visual prognosis in the sympathizing eye.

Histocompatibility antigens in sympathetic ophthalmia.

Twenty patients with histopathologically confirmed sympathetic ophthalmia (Group 1) and eight patients with "presumed sympathetic ophthalmia," based on a clinical history of bilateral uveitis occurring within four months of a perforating ocular injury (Group 2), were typed for HLA-A, HLA-B, and HLA-C antigenic determinants by a micro-lymphocytotoxicity technique. HLA antigenic determinants found in Groups 1 and 2 were compared to a control group of 107 patients with sequelae of perforating ocular injuries from accidents, intraocular surgery, or corneal ulcers (Group 3). HLA-A11 antigen showed an increased frequency of 30% in Group 1 (relative risk = 11.0; P less than .002) and an increased frequency of 32% in Groups 1 + 2 (relative risk = 10.5; P less than .0005) compared to Group 3 (frequency = 4%). This finding was validated against a second control group of 453 healthy subjects without ocular disease or trauma (Group 4). This association suggests that a genetic factor may play an important role in the pathogenesis of sympathetic ophthalmia.

Two cases of uveal metastasis from breast carcinoma in men.

We studied two cases of uveal metastasis from carcinoma of the breast in men. One patient was a 51-year-old man who developed ocular symptoms nine months after excision of a breast mass histologically diagnosed as an infiltrating ductal carcinoma. After the patient committed suicide, an autopsy disclosed metastatic lesions to the lungs, mediastinum, and chest wall. The second patient was a 49-year-old man who complained of ocular symptoms three years after undergoing mastectomy for breast carcinoma. One month after the onset of the ocular symptoms, his left eye was enucleated. Metastatic lesions were detected in the lungs and brain. More than one year after undergoing bilateral orchiectomy, and after whole-brain radiation therapy (4,500 rads) and chemotherapy, the patient has no neurologic symptoms. It appears that mammary carcinoma in men has a poorer prognosis than it does in women, probably because of two main factors: the advanced clinical stage of the disease when it is first detected and the more diffuse infiltrating character of the mass because of the scarcity of mammary tissue in men.

Cavernous sinus syndrome caused by rhabdomyosarcoma.

A 16-year-old boy was found to have a cavernous sinus syndrome secondary to rhabdomyosarcoma originating in the masseter muscle. Radiologic studies showed evidence of dissemination to the cavernous sinus without involvement of the skull base or its foramina. Despite aggressive therapy with transient improvement of his ocular palsy, the patient died within 16 months after the onset of his illness. Neuro-ophthalmic complications often develop as a result of direct extension from rhabdomyosarcoma originating in the head and neck region. However, to the best of our knowledge, this is the first report of a cavernous sinus syndrome caused by metastasis from rhabdomyosarcoma.

Cryptococcal intracerebral mass lesions: the role of computed tomography and nonsurgical management.

Cephalic computed tomography (CT) is a sensitive technique for defining certain intracerebral diseases. Four patients with cryptococcosis were evaluated with cephalic computed tomography over 3 years. All had focal, intracerebral "contrast-enhanced" lesions consistent with cryptococcal mass lesions, confirmed histopathologically in two. An analysis of 55 cases of cryptococcal intracerebral mass lesions from the literature showed that 18% of patients with these lesions associated with cryptococcal meningitis did not have specific symptoms or signs of focal intracerebral disease or increased intracranial pressure. We therefore recommend that patients with cryptococcal meningitis, regardless of localizing symptoms or signs, be considered for cephalic CT evaluation to ascertain the presence of mass lesions. Three patients in this report were treated with systemic antifungal medication without surgery. Decreased size or disappearance of these lesions was seen on sequential CT scan in all patients. We conclude that selected patients with cryptococcal intracerebral mass lesions may be managed successfully with systemic antifungal therapy alone.