Wavelength conversion and parametric amplification of optical pulses via quasi-phase-matched four-wave mixing in long-period Bragg silicon waveguides.

We present a theoretical analysis supported by comprehensive numerical simulations of quasi-phase-matched four-wave mixing (FWM) of ultrashort optical pulses that propagate in weakly width-modulated silicon photonic nanowire gratings. Our study reveals that, by properly designing the optical waveguide such that the interacting pulses copropagate with the same group velocity, a conversion efficiency enhancement of more than 15 dB, as compared to a uniform waveguide, can readily be achieved. We also analyze the dependence of the conversion efficiency and FWM gain on the pulse width, time delay, walk-off parameter, and grating modulation depth.

Macronodular congenital adrenal hyperplasia in an adult with female pseudohermaphroditism.

We report a case of previously undiagnosed congenital adrenal hyperplasia presenting with virilisation in a 59-year-old woman. Biochemical analysis revealed C-21 hydroxylase deficiency. CT demonstrated adrenal hyperplasia and a 3.8-cm adrenal nodule, raising the possibility of the development of an autonomous adrenal adenoma or carcinoma. The adrenal nodule regressed significantly with oral replacement steroid therapy over the next 30 months, indicating it to be an ACTH-dependent hyperplastic nodule and thus avoiding the need for biopsy or surgical excision. Macronodular adrenal hyperplasia should be considered in the differential diagnosis of a patient presenting with virilisation and an adrenal mass.

A prospective study of the prevalence of clear-cut endocrine disorders and polycystic ovaries in 350 patients presenting with hirsutism or androgenic alopecia.

OBJECTIVE: To determine the frequency of polycystic ovaries (PCO) on ultrasound and the incidence of clearcut endocrine disorders leading to virilization in patients complaining of hirsutism or androgenic alopecia. The major purpose was to determine a coherent policy for the routine biochemical assessment of such women. DESIGN: A prospective study of women attending a joint skin/endocrine clinic complaining of these problems. PATIENTS: Three hundred and fifty consecutive women with hirsutism and/or androgenic alopecia were assessed. MEASUREMENTS: Baseline endocrine screens were conducted on two occasions and included measurement of serum testosterone, androstenedione, dehydroepiandrosterone sulphate, sex hormone binding globulin, LH, FSH, 17-hydroxyprogesterone and PRL. The ovaries were visualized by high-resolution pelvic ultrasound scanning. RESULTS: Eight women were identified with relevant endocrine disorders; of these, one was acromegalic and one had a microprolactinoma--in both cases the association may have been fortuitous. Three had clear-cut 21-hydroxylase deficiency, one a rare hepatic enzyme deficiency (11-reductase), one a virilizing adrenal carcinoma and one a Leydig cell tumour. The latter six cases all had persistently elevated levels of serum testosterone (> 5 nmol/l). In all, 13 women had baseline testosterone levels in excess of 5 nmol/l. Polycystic ovaries were present in 81% of the cases who had erratic cycles and 52% of those with regular cycles; PCO were present in two of the women with 21-hydroxylase deficiency and in the woman with 11-oxoreductase deficiency. The Leydig cell tumour (1.2 cm diameter) was not detected on ultrasound or CT scan. CONCLUSIONS: For the exclusion of enzyme deficiencies and virilizing tumours clinical assessment and a single serum testosterone measurement will suffice.

Angiotensin II as a risk factor for cyclosporin nephrotoxicity in patients with psoriasis.

Abnormalities of the renin-angiotensin system after low-dose cyclosporin (5 mg/kg/day or less) have not been adequately defined in patients with normal kidneys. 27 patients with psoriasis were assessed before starting cyclosporin, after three months of cyclosporin (5 mg/kg/day or less) and then finally three months after finishing cyclosporin. On each occasion plasma renin activity (PRA), aldosterone, angiotensin II and atrial natriuretic peptide (ANP) were measured together with total renal blood flow (RBF), GFR and filtration fraction (FF) following an i.v. bolus injection of Tc-99m DTPA. Significant renal hemodynamic toxicity was defined as > 25% fall in RBF or > 20% fall in GFR. Using these criteria we identified 12 patients with hemodynamic toxicity (Group A) and 15 patients whose GFR and RBF did not fall significantly (Group B). In Group A a significant fall in GFR (p < 0.001) and reduction in renal blood flow (p < 0.04) were associated with significant rises in both ambulant and recumbent angiotensin II (p < 0.0005). PRA, aldosterone and ANP did not significantly alter. GFR partially recovered after withdrawal of cyclosporin although RBF remained significantly lower compared to initial values. In Group B there was no significant change in GFR or RBF although there was a reversible fall in FF (p < 0.02). There were no significant differences in angiotensin II, PRA, aldosterone or ANP. Circulating angiotensin II rises in patients who develop cyclosporin nephrotoxicity and may be responsible for mediating the hemodynamic effects.

Altered clearance of N-1 methylnicotinamide associated with the use of low doses of cyclosporine.

To improve the monitoring of patients on low doses of cyclosporine there is a need for new tests of tubular function. N-1 methylnicotinamide (NMM) is an endogenous organic cation that is secreted by the proximal tubule and its clearance can be measured. In 27 patients with psoriasis, serial measurements of NMN clearance, plasma aldosterone, plasma chloride, bicarbonate, and magnesium were compared with changes in the radionuclide measurement of glomerular filtration rate and renal blood flow before, during, and after a 3-month course of low-dose cyclosporine (< 5 mg/kg/d). N-1 methylnicotinamide clearance decreased significantly with cyclosporine only (2.5 mg/kg/d, n = 10, P < 0.01). Recovery of NMN clearance lagged behind that of glomerular filtration rate and renal blood flow. Serum magnesium decreased significantly on cyclosporine (2.5 mg/kg, n = 10, P < 0.01; 5 mg/kg, n = 9, P < 0.0001). In the whole group, plasma potassium increased significantly (n = 27, P < 0.02) and plasma aldosterone was inappropriately low. Low doses of cyclosporine in psoriasis cause a reduced clearance of NMN, hypomagnesemia, and a variable hyperchloremic acidosis. Nifedipine may alter these biochemical variables without necessarily improving renal hemodynamics. The delayed recovery of NMN clearance in comparison with renal haemodynamic measurements following cyclosporine therapy suggests that this noninvasive test of tubular function may be a marker of persisting cyclosporine nephrotoxicity and that it should be evaluated further.

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM: To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS: Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS: There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS: Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.

A quantitative immunohistochemical study of the expression of integrins by nerves in psoriatic and normal skin.

Qualitative and quantitative assessment of integrin expression by dermal nerves was made by an avidin-biotin immunoperoxidase method on snap-frozen biopsies from affected psoriatic skin, and skin from normal control subjects with no history of skin disease. Nerves expressed alpha 1, alpha 2, alpha 3, alpha 6, beta 1 and beta 4 integrin subunits, and perineural sheaths in the mid-dermis also expressed these subunits, with the exception of alpha 2. There were more upper dermal nerve segments expressing alpha 1 integrin compared with other integrins both in controls and in psoriatic skin. The greater number of nerves expressing alpha 1 integrin compared with other integrins may be due to anatomical or functional differences between groups of nerves. There were significantly more nerves expressing alpha 1, alpha 2, alpha 3, alpha 6 and beta 4 integrins in psoriatic skin compared with control skin. This generalized increase may indicate a secondary trophic effect on all nerves rather than a specific increase in one type of nerve. However, the expression of alpha 2 integrin may be significant in the pathogenesis of the psoriatic plaque, in that it was barely detectable in the normal site-matched biopsies, but much greater in psoriatic plaques. The study of the expression of adhesion molecules by neurones in psoriasis offers a new avenue for investigation of the role of neuronal hypertrophy in the initiation and maintenance of psoriatic plaques.

Chylous reflux into abdominal skin simulating lymphangioma circumscriptum in a patient with primary intestinal lymphangiectasia.

A 47-year-old man with primary intestinal lymphangiectasia developed chylous reflux into the skin of the right flank. The clinical appearance resembled lymphangioma circumscriptum with multiple dome-shaped vesicles filled with milky-white fluid which discharged on to surrounding skin. Backflow of chyle into the skin of the lower limb, perineum or external genitalia has been described as a rare finding in patients with primary lymphoedema but we believe this to be the first case involving the abdomen and the first case describing chylous reflux into the skin in a patient with intestinal lymphangiectasia.

Dogs, distemper and osteitis deformans: a further epidemiological study.

There is extensive evidence linking paramyxoviruses, notably measles and respiratory syncytial virus, with Paget's disease of bone. The epidemiology of Paget's disease does not fit with that of known human paramyxovirus infections and it is possible that the disease is a zoonosis with domestic animals acting as host. Canine distemper, a paramyxovirus of the morbillovirus family (closely related to measles) is therefore a potential candidate. We have surveyed previous pet ownership in 150 Paget's patients each of whom was matched with two general practice controls; one from an inner city practice and the other from a suburban practice both in Greater Manchester. Recall of previous dog ownership was higher in Paget's patients with differences being more marked against inner city than suburban controls. 88% of the patients had lived in the same household as a dog at some stage compared with 79% of the inner city controls (P less than 0.05) and 83% of the suburban controls (n.s.). The differences were greater in the years 1930-60 during which the proportion of patients owning dogs was largest. For Paget's patients and controls alike, recalled exposure to dogs with canine distemper appeared to cluster in certain periods between 1930 and 1960. Unexpectedly, significantly more (7 out of 22, P less than 0.01) of the patients with a known first degree relative suffering from Paget's disease had no previous history of dog ownership when compared with the other patients (10 out of 128).

Cutaneous presentation of sarcoidosis in an infant.

A 4-month-old infant developed a symptomless erythematous maculopapular rash on her abdomen spreading to involve other areas of her trunk and limbs. Skin biopsy showed the features of sarcoidosis and she later developed sarcoid uveitis and arthritis requiring systemic steroid therapy.

Exacerbation of psoriasis precipitated by an oestradiol-testosterone implant.

A 47-year-old woman developed widespread psoriasis following insertion of a combined oestradiol-testosterone implant into her anterior abdominal wall for post-oophorectomy symptoms. The rash did not resolve until the effects of the implant had worn off and recurred following insertion of a second oestradiol-testosterone implant. Implants containing oestradiol alone were tolerated. We have found no previous reports suggesting a relationship between testosterone implants and psoriasis.

Relapse of osteoporosis circumscripta as a lytic ring after treatment of Paget's disease with intravenous 3-amino-1-hydroxypropylidene-1,1-bisphosphonate.

Two patients with osteoporosis circumscripta of the skull are presented who have each been treated with a 3-month course of intravenous infusions of (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) (total dose of 185 and 375 mg), which in both cases was associated with rapid and dramatic remineralization of the porotic bone and marked clinical and biochemical remission. However, osteolytic disease reappeared (after 9 and 18 months, respectively) in both cases as an osteolytic ring showing high uptake of radiolabelled bisphosphonate on bone scan, in formerly unaffected bone just distal to the original leading edge of osteolysis. Further treatment was associated with healing of these new lesions. These cases suggest that the diseased osteoclasts entering previously normal bone are protected against the drug probably because normal bone matrix takes up relatively little APD, and that APD taken up by diseased bone behind this front confers long-term resistance to further resorption. In assessing treatment strategies with bisphosphonates for Paget's disease, the response at the leading edge of osteoporosis circumscripta may be particularly informative.