Recombinant growth hormone (GH) therapy in GH-deficient adults: a long-term controlled study on daily versus thrice weekly injections.

Currently, replacement recombinant GH (rGH) therapy in GH-deficient (GHD) adults is performed in daily injections. This modality of treatment is not complied with by the totality of GHD patients, who are supposed to receive life-long replacement. The aim of our study was to compare daily vs. thrice weekly (TIW) rGH injection effects on lipid profile, body composition, bone metabolism, and bone density in 34 GHD patients (13 women and 21 men; median age, 39 yr; range, 30-55 yr) randomly assigned to different therapeutic regimens. Group A included 18 patients receiving daily rGH injections, and group B included 16 patients receiving TIW injections of rGH. The starting dose of rGH was 10 microg/kg x day in both groups. Subsequently, the dose was adjusted to maintain serum insulin-like growth factor I (IGF-I) concentrations in the normal age-adjusted range. IGF-I levels were assessed before and after 1, 3, 6, and 12 months of rGH treatment, and lipid profile, body composition, bone metabolism, and bone density were evaluated before and after 6 and 12 months of treatment. Thirty-four healthy subjects served as controls. In the basal condition, lipid profile, body composition, bone metabolism, and bone density were significantly different in patients compared to controls. Conversely, patients included in groups A and B had similar serum IGF-I levels, lipid profile, body composition, bone metabolism, and bone density. After 3 months of rGH treatment, IGF-I levels were normalized in 15 of 18 patients (83.3%) in group A and in 7 of 16 patients (43.7%) in group B (chi2 = 4.21; P = 0.04). At this time point, serum IGF-I levels in patients in group A (202+/-57.5 microg/L) were significantly higher than those in patients in group B (155+/-45.1 microg/L; P = 0.001). After 6 months of therapy, serum IGF-I levels were normalized in all patients and were similar in both groups (223+/-35.2 vs. 212+/-41.4 microg/L, A vs. B, respectively). IGF-I levels remained normal until the 12-month follow-up. After 6 months of rGH replacement, total cholesterol, low density lipoprotein cholesterol, triglycerides, bioelectrical impedance, and body fat mass were significantly reduced, whereas high density lipoprotein cholesterol levels and lean body mass were significantly increased in both groups of patients, without any difference between them. No further change in lipid profile and body composition was observed after 12 months of treatment. Serum bone GLA protein and procollagen III levels were significantly increased after 6 months, and a downward trend was observed after 12 months of rGH replacement. However, a slight, but significant, increase in bone mineral density was observed in both groups only after 12 months (P = 0.0001). All patients in group B had good compliance to the TIW treatment, whereas 5 patients in group A had poor compliance to the treatment (chi2 = 3.2; P = 0.07). In conclusion, our randomized, prospective, and controlled study confirmed that rGH therapy with TIW injection regimen is effective in normalizing IGF-I levels and improving lipid profile, body composition, bone metabolism, and bone density. It also demonstrated that this efficacy is comparable to that observed in patients treated with daily rhGH therapy, with few side-effects and good compliance.

[Local treatment by epidermal growth factor after epikeratoplasty. A double-blind clinical trial]. / Traitement local par facteur de croissance épithélial après épikératoplastie. Etude clinique à double insu.

Epidermal growth factor is a protein which stimulates epithelial cell growth. We conducted a randomized double blind study between patients treated with PHZ102 (Inpharzam SA, Cadempino, Switzerland) containing EGF, and placebo eyedrops as topical treatment following epikeratoplasty, to evaluate the effect of EGF on corneal reepithelialization. The patients of the EGF group recovered earlier (1 to 4 days) than the patients in the placebo group (3 to 15 days). Therefore, the results obtained confirmed that EGF may reduce the time normally required for complete reepithelialization of the cornea.

Hormone replacement therapy in menopause and in premature ovarian insufficiency.

Menopause is defined by world health organization (WHO) as the permanent cessation of menstruating resulting from a loss of ovarian follicular activity, after one year of amenorrhea. It signifies the last menstrual cycle and the end of women's fertile and reproductive life. The average age for a women to undergo menopause is 51 years; unlike menarche, whose average age has decreased over the past decades, the age of menopause has remained unchanged. We can distinguish: 1) premenopause, the time interval leading up to menopause; 2) climacteric, the time interval between the reproductive e non-reproductive life; 3) premature menopause, that occurs in 1% of women. Menopause can also be induced iatrogenically as a result of surgery, medical therapy, chemotherapy and radiotherapy. Beyond the life the number of oocytes falls until there are no more suitable follicles for reproduction and the menopause ensues. At the same time, the ability of the ovary to produce hormones falls, leading to an increasing pulsatile release of FSH in order to stimulate the ovary to produce oestrogens. Menopause is characterized by different symptoms such as hot flushes, night sweats, dispareunia, prolapse, vulval itching due to vaginal atrophy and dryness, urinary incontinence, dysuria, and also the psychological aspects don't should be underestimated because of many women suffer of depression, mood instability, insomnia, fatigue and decreased libido. Long term symptoms include osteoporosis, cardiovascular and neuro-degenerative diseases. The main aim of different treatments was symptoms relief. Pharmacological agents and psychological support represent the goal for menopause treatment.

Lattice dystrophy of the cornea. A clinical and histopathologic study.

Four members of a family were affected with lattice dystrophy of the cornea. One of them showed recurrence of the disease in the corneal graft in one eye 9 years after a keratoplasty, and a very advanced stage of the disease in the fellow eye. Therefore a keratoplasty was done in this eye. The corneal button was thoroughly investigated by means of histochemistry, electron microscopy and X-ray electron microanalysis. Two young members of the family showing early signs of the disease were followed up for 2 years. It has been possible to observe the evolution of their lesions. Histopathological examinations revealed the presence of two different types of abnormal deposits under the epithelium and in the stroma. X-ray electron microanalysis of the stromal deposits revealed a substantial increase in sulphur content.

Epidermal growth factor in the topical treatment of traumatic corneal ulcers.

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of traumatic corneal ulcers have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time in the management of superficial corneal lesions.

Long-term complications of toxic epidermal necrolysis (Lyell's disease). Clinical and histopathologic study.

A case of toxic epidermal necrolysis had been observed in a 4-year-old child. This patient has been reexamined by us 21 years later. At that time a biopsy of conjunctival material and a histopathologic and ultrastructural study were done. The long-term ocular complications of the disease caused severe visual impairment with a remarkable sicca syndrome due to extensive scarring and keratinization, as confirmed also by light- and electron-microscopic features. These findings, concerning a particularly long follow-up, suggest that the ocular sequelae of this disease require continuous ophthalmological supervision many years after the acute stage of the disease.

Unilateral retinitis pigmentosa associated with exfoliation syndrome.

A case of a 71-year-old woman showing pigmentary degeneration of the retina associated with posterior subcapsular cataract in one eye, with a normal fellow eye, is presented. Clinical examinations of the patient were performed in order to rule out the various causes which are known to produce funduscopic features that mimic retinitis pigmentosa. Since these investigations were all negative, the fundus changes were interpreted as a unilateral retinitis pigmentosa. One year later, the patient was re-examined and an exfoliation syndrome was discovered in the affected eye, while the fellow eye was unchanged. An association of unilateral retinitis pigmentosa and exfoliation syndrome in the same eye can be regarded as exceptional. The possibility of a correlation of the pathogenetic mechanisms involved in the development of both conditions is discussed.

Deeply invasive squamous cell carcinoma of the conjunctiva: case report.

A 82-year-old man had a bulbar exophytic mass protruding through the lids and extending from the nasal side of the limbus to the caruncola in one eye. The lesion appeared 9 months before as a limbal nodule and showed a painless, slow evolution, ultimately leading to enucleation. The histopathologic examination of the neoplasm and eyeball showed an invasive squamous cell carcinoma of the conjunctiva which invaded the deep subepithelial tissue and reached the scleral surface. The evolution and pathologic features of this uncommon neoplasm were similar to that described in other cases previously reported. Such a clinical course is suggestive also of mucoepidermoid carcinoma of the conjunctiva, which closely resembles squamous cell carcinoma, but is more aggressive and locally invasive. However, after staining for mucin, this diagnosis was ruled out.

Epidermal growth factor in the topical treatment of herpetic corneal ulcers.

The tolerability and efficacy of epidermal growth factor (EGF) in the topical treatment of herpetic corneal ulcers in addition to topical acyclovir have been evaluated in a double-blind, placebo-controlled, randomized study in two groups of patients. The time required for complete reepithelialization of the cornea was recorded, and the data obtained were analyzed statistically. In the EGF group, the reepithelialization was significantly faster than in the control group. Tolerability of EGF was always excellent. These results indicate that EGF is safe and effective in reducing the healing time of herpetic corneal ulcers.

The iris vessels in the exfoliation syndrome: ultrastructural changes.

The ultrastructure of iris vessels in exfoliation syndrome has been investigated. Deposits of exfoliation material have been found in the vessel walls. There is evidence of different stages of pathological alterations of some vessels, culminating in the loss of endothelial cells and obliteration of the lumen associated with exfoliative deposits. These findings correlate with fluorescein angiographic alterations of the iris and stress the importance of vascular changes in this syndrome.

Posterior polymorphous dystrophy of the cornea. An ultrastructural study.

A corneal button excised from a 2-month-old infant with congenital posterior polymorphous dystrophy of the cornea, a rare disease affecting Descemet's membrane and endothelium, was examined by electron microscopy. We observed irregularly arranged, sometimes multilayered cells with marked epithelial features, lining the posterior surface of the cornea in place of the endothelium, and Descemet's membrane with focal alterations sometimes involving all of its layers. We interpreted these abnormal cells as epithelial-like cells. As these findings were in a very young patient, which is unusual, we concluded that the onset of the disease may take place in the early period of intrauterine life, corresponding to the beginning of Descemet's membrane production.

Use of the stable isotope 65Cu test for the screening of Wilson's disease in a family with two affected members.

BACKGROUND/AIMS: An improved method for the study of copper metabolism in Wilson's disease, using a stable, rather than radioactive, copper isotope (65Cu) has recently been described. We report on the use of this method for the study of a family with two members affected by Wilson's disease. SUBJECTS: The family comprised parents and four siblings: one 20-year-old male and three females, aged 22, 17 and 5 years, respectively. The boy and the 17-year-old girl both presented with liver cirrhosis. Diagnosis of Wilson's disease was suggested by elevated liver copper content and/or low caeruloplasmin levels and Kayser-Fleischer ring. METHODS: All family members were given an oral dose of 3 mg of 65Cu. Blood samples were taken at 0, 1, 2, 6, 24, 48, and 72 hours. In 4 subjects, additional blood samples were drawn at 7, 14 and 21 days after dosage. The ratio 65Cu:63Cu in serum was determined in all samples by means of Inductively Coupled Plasma Mass Spectrometry. RESULTS: The diagnosis of Wilson's disease was confirmed in the two symptomatic members by the unequivocal decrease observed in the 65Cu percent enrichment, which approached zero by 72 hours. In contrast, Wilson's disease could be definitely excluded in both siblings, one of whom only 5 years old, on the evidence of net secondary peaks, showing normal incorporation of 65Cu into caeruloplasmin. These findings were later confirmed by genetic analysis. Parents, who carried defective genes with different mutations, also showed different abnormalities of copper metabolism. CONCLUSIONS: The oral test with the stable copper isotope 65Cu is a safe, non invasive option able to exclude Wilson's disease in patients with a difficult diagnosis or in a presymptomatic stage. However, positive tests must still be confirmed by copper dosage in liver biopsies, as heterozygotes can present with severe alterations of copper metabolism, without developing symptoms of the disease. The use of this test in conjunction with genetic analysis on a larger number of heterozygous subjects may add to the understanding of the Wilson's disease defect.

Eight parathyroid glands incidentally discovered during a surgical intervention for secondary hyperparathyroidism: an unusual clinical finding.

Here we describe the uncommon case of a Caucasian male with secondary hyperparathyroidism due to 8 parathyroid glands discovered in the course of a surgical exploration. The patient (age 49 yr) with a 21-yr history of chronic renal failure came to our observation in June 1999 complaining of depression, muscle weakness, bone and joint pain, movement hindrance. The biochemical evaluation evidenced low-normal serum calcium, high phosphorus and PTH levels. The symptoms and the biochemical findings were suggestive for secondary hyperparathyroidism. The neck US revealed an increase of thyroid gland volume with diffuse hyperechogenity; two nodules of 20 and 25 mm as maximum diameter were found in the thyroid parenchyma, while 4 hypoechogenous nodules (maximum diameter ranging from 13.0 to 30.0 mm) with clean borders and anechogenous areas inside were evidenced in the rear side of the thyroid lobes. The parathyroid scan with 99mTc and 201 Tl demonstrated increased uptake bilaterally in the inferior side of the neck. The patient underwent a total parathyroidectomy with near total thyroidectomy in November 1999. Histological examination of surgical specimen evidenced 6 hyperplastic parathyroid glands in back side of the 2 lobes (3 on the right and 3 on the left), and the examination of the thyroid gland showed 2 hyperplastic parathyroids (5 mm and 15 mm maximum diameter) into the 2 nodules previously evidenced by US. The physiopathological and clinical and therapeutic implications of this observation are discussed.