Skeletal health in patients with differentiated thyroid carcinoma.

Osteoporosis and fractures are important comorbidities in patients with differentiated thyroid cancer (DTC), with potential negative impact on quality of life and survival. The main determinant of skeletal fragility in DTC is the thyrotropin (TSH)-suppressive therapy, which is commonly recommended to prevent disease's recurrence, especially in patients with structural incomplete response after thyroid surgery and radio-iodine therapy. TSH-suppressive therapy can stimulate bone resorption with consequent bone loss, deterioration of bone microstructure and high risk of fragility fractures. The skeletal effects of TSH-suppressive therapy may be amplified when thyroid cancer cells localize to the skeleton inducing alterations in bone remodelling, impairment of bone structure and further increase in risk of fractures. The management of skeletal fragility in DTC may be challenging, since prediction of fractures is a matter of uncertainty and data on effectiveness and safety of bone-active agents in this clinical setting are still scanty. This review deals with pathophysiological, clinical and therapeutic aspects of skeletal fragility of patients with DTC.

Secondary hyperparathyroidism and thoracic vertebral fractures in heart failure middle-aged patients: a 3-year prospective study.

PURPOSE: Vertebral fractures (VFs) were described in elderly patients with heart failure (HF) whereas their prevalence and determinants in younger HF patients are still unknown. This study aimed at assessing whether secondary hyperparathyroidism (SHPT) may influence the risk of VFs in middle-aged patients with HF. METHODS: 84 patients (44 males, median age 48.5 years, range 43-65) with HF were prospectively evaluated at the baseline and after 36-month follow-up for bone mineral density (BMD) and VFs by quantitative morphometry on chest X-rays. Serum PTH, calcium, 25-hydroxyvitamin D and 24-h-urinary calcium were evaluated at the baseline and every 6-12 months during the study period. RESULTS: At baseline, SHPT, hypovitaminosis D and VFs were found in 43 patients (51.2%), 73 patients (86.9%) and 29 patients (34.5%), respectively. SHPT was associated with VFs at baseline [inverse probability-weighted (ipw) odds ratio (OR) 12.2, p < 0.001]. Patients were treated with vitamin D3 alone (56%), vitamin D3 plus calcium carbonate (21.4%), calcitriol alone (4.8%), bisphosphonates plus vitamin D3 (8.3%) or a combination of bisphosphonates, vitamin D3 and calcium carbonate (9.5%). At the end of follow-up, hypovitaminosis D was corrected in all patients, whereas 19/84 patients (22.6%) had persistent SHPT. During the follow-up, 16 patients developed incident VFs which resulted to be associated with baseline SHPT (ipw OR 55.7, p < 0.001), even after adjusting from BMD change from baseline to follow-up (ipw OR 46.4, p < 0.001). CONCLUSIONS: This study provides a first evidence that SHPT may be a risk factor for VFs in middle-aged patients with HF.

Endocrine and metabolic complications in children and adolescents with Sickle Cell Disease: an Italian cohort study.

BACKGROUND: Children with Sickle Cell Disease (SCD) show endocrine complications and metabolic alterations. The physiopathology of these conditions is not completely understood: iron overload due to chronic transfusions, ischemic damage, and inflammatory state related to vaso-occlusive crises may be involved. Aims of this study were to evaluate the growth pattern, endocrine complications, and metabolic alterations and to detect the relationship between these conditions and the SCD severity in affected children and adolescents. METHODS: Fifty-two children and adolescents with SCD [38 homozygous sickle hemoglobin (HbSS) and 14 heterozygous sickle hemoglobin (HbSC); age range 3-18 years] were recruited. Anthropometric [height, body mass index (BMI), arm span, sitting height, target height (TH), and pubertal status] and laboratory [blood cell counts, hemolysis indices, metabolic and nutritional status indices and hormonal blood levels] data were evaluated. The SCD severity was defined according to hematological and clinical parameters. RESULTS: Height-SDS adjusted for TH and BMI-SDS were significantly higher in HbSC children than in HbSS ones. Forty-eight out of 52 patients (92%) had at least one metabolic and/or endocrine alteration: insufficiency/deficiency of vitamin D (84.7%), insulin resistance (11.5%), growth hormone deficiency (3.8%), subclinical hypothyroidism (3.8%), and hypogonadism (1.9%). Levels of vitamin D were significantly and negatively correlated with clinical indicators of the SCD severity. Subjects with HbSS genotype show significant lower levels of both insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein 3 than children with HbSC. In the study population IGF-1 values were significantly and positively correlated with Hb and negatively with lactate dehydrogenase. CONCLUSIONS: Metabolic alterations and endocrine complications are very common in children and adolescents with SCD. A regular follow-up is necessary to identify subjects at risk for complications to precociously start an appropriate treatment and to improve the quality of life of SCD patients.

Fungal infections of the central nervous system and paranasal sinuses in onco-haematologic patients. Epidemiological study reporting the diagnostic-therapeutic approach and outcome in 89 cases.

Invasive fungal infections (IFI) of the Central Nervous System (IFI-CNS) and Paranasal Sinuses (IFI-PS) are rare, life-threatening infections in haematologic patients, and their management remains a challenge despite the availability of new diagnostic techniques and novel antifungal agents. In addition, analyses of large cohorts of patients focusing on these rare IFI are still lacking. Between January 2010 and December 2016, 89 consecutive cases of Proven (53) or Probable (36) IFI-CNS (71/89) and IFI-PS (18/89) were collected in 34 haematological centres. The median age was 40 years (range 5-79); acute leukaemia was the most common underlying disease (69%) and 29% of cases received a previous allogeneic stem cell transplant. Aspergillus spp. were the most common pathogens (69%), followed by mucormycetes (22%), Cryptococcus spp. (4%) and Fusarium spp. (2%). The lung was the primary focus of fungal infection (48% of cases). The nervous system biopsy was performed in 10% of IFI-CNS, and a sinus biopsy was performed in 56% of IFI-PS (P = 0.03). The Galactomannan test on cerebrospinal fluid has been performed in 42% of IFI-CNS (30/71), and it was positive in 67%. Eighty-four pts received a first-line antifungal therapy with Amphotericine B in 58% of cases, Voriconazole in 31% and both in 11%. Moreover, 58% of patients received 2 or more lines of therapy and 38% were treated with a combination of 2 or more antifungal drugs. The median duration of antifungal therapy was 60 days (range 5-835). A surgical intervention was performed in 26% of cases but only 10% of IFI-CNS underwent neurosurgical intervention. The overall response rate to antifungal therapy (complete or partial response) was 57%, and 1-year overall survival was 32% without significant differences between IFI-CNS and IFI-PS. The overall mortality was 69% but the IFI attributable mortality was 33%. Mortality of IFI-CNS/PS remains high but, compared to previous historical data, it seems to be reduced probably due to the availability of newer antifungal drugs. The results arising from this large contemporary cohort of cases may allow a more effective diagnostic and therapeutic management of these very rare IFI complications in haematologic patients.

Early detection of biochemically occult autonomous thyroid nodules.

OBJECTIVE: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach. DESIGN AND METHODS: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I131) uptake (RAIU). RESULTS: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425). CONCLUSIONS: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients.

Congenital neuroblastoma with symptoms of epidural compression at birth.

The occurrence of congenital neuroblastoma presenting at birth with symptoms of epidural compression secondary to spinal canal invasion is rare. Almost all cases reported in the literature have survived from the tumor but suffer severe sequelae, with the exception of the 2 most recently described whose birth was anticipated. The 3 cases of this article have been followed for a minimum of 5 years with the aim to describe their definitive late complications. In none of these cases had the routine ultrasound scan performed in third trimester of pregnancy discovered a tumor mass, nor had it shown abnormal fetal movements. All had leg hypotonia detected on the first day of life. In all, both primary and intraspinal tumors responded well to chemotherapy. All survive with motor deficit and severe bladder dysfunction despite early physiotherapy. Scoliosis has developed in the case with the longest follow-up. The description of these patients enforces the importance of early diagnosis of tumor masses in late pregnancy. Neonatologists should be aware of this rare clinical entity and take it into account in the differential diagnosis with other conditions of early-onset hypotonia. On the other hand, obstetric sonologists should be aware of the possibility to detect such rare tumors in late pregnancy, as anticipation of delivery may reduce the risk of late sequelae.

Individually-tailored thyroxine requirement in the same patients before and after thyroidectomy: a longitudinal study.

OBJECTIVE: Thyroxine (T4) requirement after total thyroidectomy for differentiated thyroid carcinoma (DTC) is a debated issue. As most of the studies in the area have been retrospective and/or performed with heterogeneous therapeutic approaches, we designed our study to determine T4 requirement in the same patients and treatment settings, before and after total thyroidectomy. DESIGN, PATIENTS AND METHODS: This was a longitudinal study including 23 goitrous patients treated with T4 in an individually tailored fashion. All patients exhibited a stable TSH (median TSH = 0.28 mU/l) at a stable T4 dose for at least 1 year before surgery (median T4 dose = 1.50 µg/kg per day). The patients underwent total thyroidectomy based on cancer suspicion or compressive symptoms. Eventually diagnosed as having DTC (pT1b-pT2N0) and following surgical and radiometabolic treatment, they were treated with the same pre-surgical doses of T4. RESULTS: Three months after surgery,using the same pre-surgical dose, median TSH increased up to 5.38 mU/l (P<0.0001) and so the T4 dose had to be increased (median T4 dose = 1.95 µg/kg per day; +30%; P < 0.0001). Once divided by patients' age, we observed that, after thyroidectomy and maintaining the same pre-surgical dose, serum TSH significantly increased both in younger and in older patients (median TSH = 4.57 and 6.11 mU/l respectively). Serum TSH was restored to the pre-surgical level by increasing the dose up to 1.95 and 1.77 µg/kg per day (+25 and +21%) respectively. CONCLUSIONS: Following the same treatment regimen, a thyroidectomized patient requires one-third higher therapeutic T4 dose than before surgery. Despite this increase, the dose of T4 needed in our patients remains significantly lower than that previously described in athyreotic patients.

Management of community-acquired pneumonia by trained family general practitioners.

SETTING: Community-acquired pneumonia (CAP) is a respiratory health disease with a high prevalence in the general population. Family general practitioners (GPs) can play an important role in CAP management by reducing unnecessary hospital admissions and, consequently, national health costs. OBJECTIVE: To assess CAP management by trained GPs. DESIGN: A course in CAP management, including a risk classification method based only on clinical criteria, was developed within the framework of an educational programme. GPs who participated in the programme (n = 220) were asked to collect data on their CAP patients. RESULTS: GPs (n = 94, response rate 42.7%) provided information on 370 patients (50% males, aged 18-93 years). The numbers of patients judged to be at low, moderate and high risk were 81%, 13% and 6%, respectively. The admission rate was 19.5%. All home-treated patients had good clinical outcomes. Home treatment was based on quinolones (62%), beta-lactams (23%) and macrolides (15%). The attributable economic mean cost of antibiotic home treatment was euro 96 per episode (standard deviation 71, range 17-445). CONCLUSIONS: The good outcomes suggest that GPs managed their CAP patients well, adhering to the content of the CAP management course. The risk evaluation of patients admitted to hospital, based exclusively on clinical elements, was consistent with more complex classification.

Diagnostic performance of tear function tests in Sjogren's syndrome patients.

OBJECTIVE: To evaluate the diagnostic performance of the tests included in primary Sjogren's syndrome (SS-I) diagnostic criteria (Schirmer I, break-up time, vital dye staining) and to compare them with other examinations related to the ocular surface status. METHODS: Clinical and cytological data were collected from 177 patients (62 SS-1, 56 non-SS autoimmune diseases, 59 Sicca syndrome). Tear tests included: a validated questionnaire on symptoms, Schirmer I, Jones test, Ferning test, BUT, corneal aesthesiometry, tear clearance test, lissamine green staining, impression conjunctival cytology. Data were statistically evaluated and sensitivity, specificity, likelihood ratio (LR+), receiver-operating characteristics (ROC) curves were calculated for each test. RESULTS: Data showed a poor diagnostic performance of Schirmer test I (sensitivity 0.42; specificity 0.76; LR+1.75) and BUT (sensitivity 0.92; specificity 0.17; LR+1.11) (area under the curve in ROC analysis <0.58). Validated subjective symptoms questionnaire (sensitivity 0.89; specificity 0.72; LR+3.18), Jones test (sensitivity 0.60; specificity 0.88; LR+5), corneal aesthesiometry (sensitivity 0.80; specificity 0.67; LR+2.42), and tear clearance test (sensitivity 0.63; specificity 0.84; LR+3.93), all exhibited a high diagnostic performance (area under the curve in the ROC analysis always >0.70). Lissamine green staining exhibited the best performance (sensitivity 0.63; specificity 0.89; LR+5.72) but the result could be distorted by an incorporation bias. CONCLUSIONS: Our data suggest to implement the items for ocular signs and symptoms contained in many SS-I diagnostic criteria with the use of a validated questionnaire, performance of Jones test, corneal aesthesiometry measurement, and tear clearance rate evaluation.

Optical coherence tomography, frequency-doubling technology, and colour Doppler imaging in ocular hypertension.

PURPOSE: To study in ocular hypertension (OH) the retinal nerve fibre layer (RNFL) with optical coherence tomography (OCT) and the neuronal function with frequency-doubling technology (FDT) to assess which of the two methods was more sensitive in detecting early glaucomatous damage. Furthermore, a colour Doppler imaging (CDI) of the optic nerve was carried out to highlight any correlation with RNFL thickness and FDT abnormality. MATERIALS AND METHODS: We enrolled 28 ocular hypertensive patients who underwent OCT of the RNFL and FDT. Moreover, we performed a CDI of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary arteries (PCAs). RESULTS: The patients with OH following OCT revealed a significant thinning in the RNFL as compared to the control group only in the inferior quadrant: 122.250+/-14.091 vs131.750+/-10.729 mum (P<0.045). As regards FDT, there was a significant difference between the two groups only for pattern standard deviation (PSD): 3.873+/-1.488 vs1.938+/-0.704 dB (P<0.044). In OH and in the control group, CDI resistance index (RI) in the OA was 0.768+/-0.012 vs0.745+/-0.019 (P<0.022), in the CRA was 0.66+/-0.012 vs0.645+/-0.019 (P<0.032), and in PCAs was 0.673+/-0.039 vs0.622+/-0.012 (P<0.037). The OCT had a sensitivity of 83% but only in the inferior RNFL quadrant. The FDT-PSD revealed a sensitivity of 85%. CONCLUSIONS: Both FDT and OCT detect early glaucomatous damage with a slightly superior sensitivity of FDT vsOCT. The CDI measurements suggest that circulatory abnormalities may have a role in the development of OCT and FDT damage.

The use of nerve growth factor in surgical wound healing of the cornea.

BACKGROUND: Recent studies have shown how the topical application of nerve growth factor (NGF) has led to the repair of neurotrophic corneal ulcers with recovery of corneal surface sensitivity. The biological effect of NGF, at a corneal level, is mediated by the presence of specific receptors localized on the surfaces of the corneal and conjunctival cells. OBJECTIVES: To evaluate the efficacy of NGF to promote corneal wound healing after cataract surgery. METHODS: Thirty patients were divided into two groups (groups A and B) and underwent cataract surgery. After surgery patients in group A received 1 drop of NGF solution (10 microg of NGF dissolved in 50 microl of saline solution, 0.9% of sodium chloride) in the conjunctival fornix every 2 h (from 6 a.m. to 12 p.m.) for 2 weeks and then 4 times a day for another week. The patients in group B received 1 drop of hyaluronic acid 0.2% eye drops in the conjunctival fornix every 2 h for 2 weeks and then 4 times a day for another week. With optical coherence tomography (OCT) we evaluated the corneal thickness at the side of the surgical wound, the endothelial cell count and the incision line in the stroma 1, 7 and 21 days after surgery. RESULTS: Before surgery in group A and in group B, the endothelial cell count was 2,607.4 +/- 261.0 versus 2,602.0 +/- 266.6 (p < 0.991), and the temporal cornea edge thickness was 639.2 +/- 24.7 versus 644.4 +/- 31.9 microm (p < 0.605), respectively. At 24 h after surgery, the results were: 2,523.2 +/- 280.5 versus 2,528.2 +/- 235.7 (p < 0.988) and 804.4 +/- 29.5 versus 802.6 +/- 35.0 microm (p < 0.953). After 7 days the cell count values were: 2,511.4 +/- 229.8 versus 2,490.0 +/- 230.4 (p < 0.361) and corneal thickness 713.6 +/- 16.5 versus 771.4 +/- 36.5 microm (p < 0.047). Finally, 21 days after surgery, the number of endothelial cells was 2,540.2 +/- 237.3 versus 2,503.4 +/- 224.5 (p < 0.382) and corneal thickness 645.2 +/- 22.6 versus 704.2 +/- 11.8 microm (p < 0.002). In the patients treated with NGF, on day 21, we found with OCT a complete wound healing, and the stromal incision was not visible. CONCLUSIONS: This clinical experience shows that the topical administration of NGF is effective in accelerating the healing of surgical corneal wounds.

Quality of generated diagnosis related groups in Italian Respiratory Intermediate Care Units.

BACKGROUND: To date we lack official data on tipology of Diagnosis Related Groups (DRGs) and their quality in Italian Respiratory Intermediate Care Units (RICUs). AIM: The objective of the study was to collect data on the activity of 26 Italian RICUs and to evaluate the quality of the DRGs generated. METHODS: The primary and secondary diseases, the procedures carried out and their coding using the ICD9 system (valid Italy until 2000) were collected from the discharge forms of patients admitted to RICUs. To obtain the DRG, these codes were automatically recoded in the ICD9-CM classification system by Grouper 10. Afterwards, the same diseases and procedures were directly processed by the ICD9-CM classification system. Finally, in order to evaluate the quality of care, the DRGs generated by the ICD9 classification system were compared to DRGs generated by the ICD9-CM classification system. RESULTS: The average weight of the patients cared for in an Italian RICU was 2.05 using the ICD9 classification system and 2.53 using the ICD9-CM classification system. Some non-complicated DRGs (80-97) or non specific DRGs (101-102) were set to zero; others, like DRG 87 appear due to the ability of the ICD9-CM classification system to recognise and accept the fifth digit of the Respiratory Failure code (518.81). The difference in terms of DRG scores generated by the two codification systems was 360.5 DRG points in favour of ICD9-CM. More than 1 million Euro of reimbursements have been lost, as the average national reimbursement for each DRG score is Euro 2,943.80. CONCLUSION: Severe pulmonary diseases determined the case mix of patients cared for in the Italian RICUs during the observed period. The Italian RICUs offer high quality assistance and are characterised by high mean weight per treated patient. However, the activity has been under-estimated due to the low sensitivity of the ICD9 classification system used in the recognition of the real disease and in the correct generation of relative DRG. The ICD9 classification system penalised the recognition of respiratory failure in particular.

Prostaglandin analogs and blood-aqueous barrier integrity: a flare cell meter study.

PURPOSE: To study, with an objective method, inflammation of the anterior segment of the glaucomatous eye after treatment with latanoprost, travoprost and bimatoprost. MATERIALS AND METHODS: Sixty patients with chronic open-angle glaucoma aged between 38 and 76 years (mean 64.0 +/- 12.2) were randomly assigned to latanoprost 0.005, travoprost 0.004 and bimatoprost 0.03%. The study period lasted 6 months. Intraocular pressure (IOP) was measured every 2 weeks. We studied the intraocular inflammation before and after 3 and 6 months of therapy with an instrument composed of a He-Ne laser beam system, a photomultiplier mounted on a slitlamp microscope and a computer. This flare meter allows objective determination of the flare and the number of cells in the aqueous of the anterior chamber. RESULTS: At the baseline, IOP was 26.4 +/- 3.6 mm Hg. After 3 months of treatment, mean IOP in the latanoprost group was 17.9 +/- 0.3 mm Hg (p < 0.001) with a mean cellularity of 12.638 +/- 3.284 photons/ms (p < 0.001). The travoprost group had an IOP of 17.2 +/- 0.3 mm Hg (p < 0.001) with a cellularity of 9.719 +/- 1.927 photons/ms (0.001). Finally, IOP in the bimatoprost group was 17.6 +/- 0.5 mm Hg (p < 0.001) with a cellularity of 6.138 +/- 1.475 photons/ms (p < 0.032). After 6 months of treatment, IOP in the latanoprost group was 18.1 +/- 0.3 (p < 0.001), in the travoprost group 17.3 +/- 0.3 (p < 0.001) and in the bimatoprost group 17.7 +/- 0.5 mm Hg (p < 0.001), whereas cellularity was 11.838 +/- 3.218 (p < 0.001), 8.950 +/- 3.692 (p < 0.001) and 7.617 +/- 2.603 photons/ms (p < 0.001), respectively. After 3 months, the travoprost (p < 0.013) and the bimatoprost groups (p < 0.001) had less flare compared with the latanoprost group and this remained so even at 6 months. When we compared the travoprost group with the bimatoprost group, we found significantly less flare at 3 months in the bimatoprost group (p < 0.001) but not at 6 months (p < 0.246). CONCLUSIONS: The flare meter analysis shows that the eyes treated with bimatoprost and travoprost have a less significantly broken blood-aqueous barrier and their anterior chamber is also significantly less inflamed.

Pseudodoubling of the optic disc: a colour Doppler imaging study.

Pseudodoubling of the optic disc is a rare clinical presentation. In these cases it is necessary to exclude retinal coloboma or atrophy following vascular or infectious diseases. We present a case of pseudodoubling of the optic disc in a woman with type 2 diabetes and arterial hypertension. Ophthalmoscopic examination of the fundus showed a disc-like lesion in the right eye and a diabetic retinopathy in the left eye. The lesion was evaluated with fluorescein angiography, neuroradiological and colour Doppler imaging investigations. Colour Doppler imaging confirmed the angiographic findings of anomalous vascularisation of the pseudopapilla and provides an analysis of the choroidal vessel anastomosis between the optic disc and the retinal lesion, revealing that the pseudodoubling in this patient was the result of a chorioretinal coloboma.

Effects of oxidation and cytosolic redox conditions on excitation-contraction coupling in rat skeletal muscle.

In this study the effects of oxidation and reduction on various steps in the excitation-contraction (E-C) coupling sequence was examined in mammalian skeletal muscle. In mechanically skinned fast-twitch fibres, electric field stimulation was used to generate action potentials in the sealed transverse-tubular (T-) system, thereby eliciting twitch responses, which are a sensitive measure of Ca2+ release. Treatment of fibres with the oxidant H2O2 (200 microM and 10 mM) for 2-5 min markedly potentiated caffeine-induced Ca2+ release and the force response to partial depolarisation of the T-system (by solution substitution). Importantly, such H2O2 treatment had no effect at all on any aspect of the twitch response (peak amplitude, rate of rise, decay rate constant and half-width), except in cases where it interfered with the T-system potential or voltage-sensor activation, resulting in a reduction or abolition of the twitch response. Exposure to strong thiol reductants, dithiothreitol (DTT, 10 mM) and reduced glutathione (GSH, 5 mM), did not affect the twitch response over 5 min, nor did varying the glutathione ratio (reduced to oxidised glutathione) from the level present endogenously in the cytosol of a rested fibre (30:1) to the comparatively oxidised level of 3:1. In fibres that had been oxidised by H2O2 (10 mM) (or by 2,2'-dithiodipyridine, 100 microM), exposure to GSH (5 mM) caused potentiation of twitch force (by approximately 20 % for H2O2); this effect was due to the increase in the Ca2+ sensitivity of the contractile apparatus that occurs under such circumstances and was fully reversed by subsequent exposure to 10 mM DTT. We conclude that: (a) the redox potential across the sarcomplamsic reticulum has no noticeable direct effect on normal E-C coupling in mammalian skeletal muscle, (b) oxidising the Ca2+-release channels and greatly increasing their sensitivity to Ca2+-induced Ca2+ release does not alter the amount of Ca2+ released by an action potential and (c) oxidation potentiates twitches by a GSH-mediated increase in the Ca2+ sensitivity of the contractile apparatus.

Frequency doubling perimetry in ocular hypertension and chronic open angle glaucoma.

The authors have studied the reliability of frequency doubling perimetry (FDP) in screening glaucomatous disease and in ocular hypertension. The study was made on 30 patients affected by chronic simple open-angle glaucoma (COAG) and 30 patients with ocular hypertension. MD and PSD variations were evaluated after a W/W perimetry and after FDP. In the COAG patients, FDP confirmed the perimetric alterations found by the W/W method. In the ocular hypertensive patients, with FDP we found a significant PSD increase over that found by the W/W technique: 4.051 +/- 0.822 against 2.501 +/- 0.928 (P < 0.001). FDP can therefore be put forward as a valid instrument for screening even precocious perimetric defects.

Dryness symptoms, diagnostic protocol and therapeutic management: a report on 1,200 patients.

PURPOSE: To report the diagnostic and therapeutic data obtained from 1,200 patients suffering from dry eye symptoms not due to Sjögren's syndrome or other auto-immune diseases. METHODS: Schirmer test I, ferning test, breakup time, vital dye staining, brush and imprint cytology were performed; data were grouped into diagnostic profiles, and the therapy was prescribed according to these. RESULTS: Eight diagnostic profiles were identified. Dry eye was diagnosed in 57.1% of patients; the remaining 42.9% were found to suffer from eye discomfort or conjunctivitis of different aetiologies. CONCLUSIONS: Subjective symptoms of dryness can hide diseases other than dry eye; combined clinical and laboratory tests are requested to make a diagnosis. Our experience indicates that a therapy prescribed on the basis of diagnostic profiles provides relief in 79.1% of cases.

The biocompatibility of silicone, fluorosilicone and perfluorocarbon liquids as vitreous tamponades. an ultrastructural and immunohistochemical study.

PURPOSE: To investigate the interactions occurring at the interface between some currently used vitreous tamponading substances and the ocular tissues, in an early follow-up after surgery. METHODS: Adult albino rabbit eyes underwent vitrectomy and were injected intravitreally with silicone oils at 1,000 or 3,000 cSt, fluorosilicone oil and perfluorodecalin. Different morphological techniques (light microscopy, scanning and electron microscopy, immunohistochemistry) were applied. RESULTS: All the tested materials, although non-toxic, penetrate the ocular tissues also at the anterior segment level, and in the long-term follow-up this can yield functional impairment. No massive inflammation has been detected in the zones in contact with the materials, but immunoglobulins and complement fractions are anyway present in the stroma of various tissues and around the droplets of emulsified materials, suggesting a local immune reaction. CONCLUSIONS: Data from this study confirmed that a permanent vitreous substitute, showing a perfect biocompatibility, still does not exist. The indication to remove the tamponading substance within 2 months after the surgery emerges from this investigation, confirming previous studies. Despite some negative features, silicone oil still appears the most biocompatible material for vitreous replacement.

Different Ca2+ releasing action of caffeine and depolarisation in skeletal muscle fibres of the rat.

1. The relative abilities of caffeine and transverse tubular (T-) system depolarisation to induce Ca2+ release in mammalian skeletal muscle were compared in mechanically skinned fibres of the rat, in order to determine whether normal excitation-contraction (E-C) coupling is achieved by up-regulating the Ca2+-induced Ca2+ release process, as caffeine is known to do. 2. Caffeine triggered Ca2+ release in soleus (slow-twitch) fibres at much lower concentrations than in extensor digitorum longus (EDL) (fast-twitch) fibres when the sarcoplasmic reticulum (SR) of each type was loaded with Ca2+ at close to endogenous levels. The difference in caffeine sensitivity resulted at least in part from the SR being loaded endogenously at near maximal capacity in soleus fibres but at less than half of maximal capacity in EDL fibres. The caffeine sensitivity could be reversed by reversing the relative level of SR loading. 3. The ability of caffeine to induce Ca2+ release was markedly reduced by lowering the level of SR loading or by raising the free [Mg2+] from 1 to 3 mM. Caffeine, even at 30 mM, triggered little or no Ca2+ release in EDL fibres (a) at 1 mM (physiological) Mg2+ when the SR was loaded at two-thirds or less of the endogenous level, and (b) at 3 mM Mg2+ when the SR was loaded at close to the endogenous level. In contrast, depolarisation potently elicited Ca2+ release under these conditions in the same fibres. 4. The inability of 30 mM caffeine to induce Ca2+ release under certain conditions was not attributable to desensitisation or inactivation of the release channels, because there was no response even upon initial exposure to caffeine and depolarisation always remained able to trigger Ca2+ release. It instead appeared that caffeine was a relatively ineffectual stimulus in EDL fibres except under conditions where (a) the SR was heavily loaded, (b) the free [Mg2+] was low, or (c) a high [Cl-] was present. 5. These results show that the normal E-C coupling mechanism in mammalian skeletal muscle does not involve just enhancing Ca2+-induced Ca2+ release, and evidently requires the removal or bypassing of the inhibitory effect of Mg2+ on the Ca2+ release channels.