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This contribution discusses the methodology and results of a research on sediment dynamics in the coastal areas close to the three inlets of the Venice Lagoon in normal (tide-governed) and storm conditions. The study, which is based on experimental investigations and mathematical models, attempts to improve the knowledge on suspended sediment transport along the littorals and its interactions with tidal exchanges at the inlets. The trend of littoral currents and the distribution of suspended particulate matter (SPM) along the coastline, which affect the solid fluxes through the inlets, have been investigated within specific field measurements by using Acoustic Doppler Current Profilers (ADCP). These instrument, mounted on a survey boat permit to acquire a bi-dimensional representation of the current field and backscatter. This last is related to the concentration of the scatterers (SPM) in the water column via calibration against concentration measured in water samples collected during the transect profiling. The modeling study apply an integrated 3-D model which permits to describe the dynamics of dispersion and transport of sediments. The considered numerical models, in increasing order of complexity are: a finite-elements hydrodynamical model (SHYFEM), a dispersion and diffusion module for contaminants, a finite-elements spectral wave model (WWM) and a sediment transport model (SEDTRANS05). The integrated experimental-modelling study permitted to investigate the effects of the modified morphology of the inlets on the velocity field induced by the tide. It also allowed a detailed study of sediment transport in the areas adjacent to the inlets during two storm events.

Most patients with advanced prostate cancer respond to androgen inhibition with or without antiandrogens. Progression to androgen-independent prostate cancer takes 5-7 years and is characterized by biochemical or diagnostic changes, despite testosteronemia levels similar to those after castration. Dutasteride, a 5-alfa-reductase types 1 and 2 inhibitor, is used in the treatment of benign prostatic hyperplasia (BPH). In prostate cancer, 5-alfa-reductase type 1 expression is greater than in BPH, but no differences in 5-alfa-reductase type 2 expression have been observed between metastatic prostate cancer and BPH. The higher levels of the two isozymes in metastatic and in recurrent prostate cancer after androgen withdrawal may reflect a selective adaptive mechanism to the amplification of remaining androgen signals. The aim of this prospective study was to evaluate the clinical utility of dutasteride in the treatment of hormone refractory prostate cancer.Between March 2005 and December 2007, 8 patients with hormone refractory prostate cancer were evaluated prospectively. Following antiandrogen withdrawal and subsequent increase in PSA, 5 patients received docetaxel plus prednisone and 3 received ketoconazole plus hydrocortisone. The regimen was a single administration of 2 tablets of 0.5 mg dutasteride/die. Therapeutic response was defined as a50% reduction in PSA or a 75% reduction at 4 weeks after the start of therapy.The mean duration of follow-up was 9 months (range, 21-24 months). A reduction50% or75% in PSA was noted in 4 and 6 patients, respectively. Bone scintigraphy detected no normalization of bone lesions; computed tomography scanning showed no partial response to treatment. The mean duration of response was 6.9 months (range, 0-21 months). Two (25%) of the 8 patients died at 6 and 10 months, respectively, neither of which had responded to dutasteride treatment. Only 1/8 patients reported experiencing dyspepsia during the study period.The activity of 5-alfa-reductase types 1 and 2 is expressed in the epithelial cells of the prostate, the stroma, and the prostate tumor. The genetic expression of fatty acid synthesis is influenced by dutasteride, which inhibits it by blocking the pathway that regulates sterol protein binding which, in turn, regulates androgen stimulation. The addition of a dual inhibitor of 5-a-reductase types 1 and 2 to antiandrogen therapy may further inhibit tumor growth, thus reducing the concentration of intracellular dihydrotestosterone, which is the primary androgen mediator of PSA gene expression in prostate tumor cell lines. These data support the rationale for the use of dutasteride in the treatment of hormone refractory prostate cancer. The study findings show that dutasteride is useful in the treatment of hormone refractory prostate cancer.

HPV infection is the most common sexually transmitted disease today and is strongly related to cervical cancer. We studied 1500 women in a limited area of the Calabria region to determine the best method of screening for cevical cancer.

The present work reports the preliminary results of the analysis based on the time series from the ADCPs (Acoustic Doppler Current Profilers), employed in the inlets of the Venetian Lagoon. Basically, in situ data originate from two types of measurements, namely, point measurements from the bed-mounted sensors and periodic measurements along the entire cross section carried out by means of a vessel-mounted instrument. Both types of instrumental installation acquire current velocity and backscattered acoustic signal, which is then calibrated for estimating the suspended sediment concentration. Discharge is obtained from the time series of current velocity in the inlet (index velocity method). Solid flux is then a product of the discharge and suspended sediment concentration. The time series of the water and sediment fluxes are updated for the Lido inlet, which has the longest time record, while for the other two inlets data are available for shorter time intervals. Simultaneous data from all the three inlets are available only for a time period of about three months (February - April 2006). The present analyses lead to the following considerations: the linear relationship between index velocity and discharge has changed in the Chioggia inlet, and the possible cause could be the narrowing of the cross section due to the construction of a navigation lock in correspondence to the ADCP location; the estimates of the solid flux at the Lido inlet, originating from the calibration of the backscattered signal from bed-mounted and vessel-mounted sensors are, prevalently, in a good agreement; exceptionally high discrepancies in several cases could be due to the asymmetry of the solid load distribution over the section, which increases with the action of the waves during particular weather conditions. A preliminary budget of the sediment transport between the lagoon and the open sea for the period February - April 2006 (without exceptional meteorological events) highlights an export of about 60000 tons of suspended materials from the lagoon toward the open sea, with a predominant contribution through the Lido inlet.

Structure, adsorption properties and surface reactivity of Cu-ZnO/ZrO2 catalysts (ZrO2 loading, 43 wt%; Zn/Cu (at/at), 0.0-2.8) have been probed by BET, XRD, TPR, N2O-titration, FTIR and TPD measurements of H2, CO and CO2. Characterization data indicate that ZnO promotes the dispersion and reactivity of metal copper to oxygen, while both ZnO and ZrO2 support markedly enhance the surface CO2 adsorption. A synergism of metal Cu hydrogenation and oxide basic sites discloses the primary role of the metal/oxide interface on the functionality of Cu-ZnO/ZrO2 catalysts in the CO2 to CH3OH hydrogenation reaction. The extent of the oxide/metal interface, probed both by Cud+/Cu0 and oxide-to-metal surface area (OSA/MSA) ratios, provides a normalization of the Cu site specific activity (TOF) in a wide range (3-60%) of metal dispersion proving the dual-site nature and, then, the formal structure-insensitive character of the title reaction.

Two methods for conversion of the backscatter intensity provided by the bottom-mounted Acoustic Doppler Current Profiler (ADCP) situated in Lido inlet, and related results, are outlined in this paper. The time series of the backscatter intensity from the fixed ADCP is calibrated against the in situ data collected through the extensive series of field measurements. The two time series of concentration estimates are obtained; the former is based on water samples, and the latter on concentration estimates obtained from the calibration of the backscatter measured along transects acquired by a boat-mounted ADCP. The advantage of the first method is in using the concentration determined directly from the water samples, · but it describes the vertical profile with a scarce resolution. The second method provides finer vertical resolution, but includes the possible effects of the lateral gradients in the distribution of suspended particles in the investigated section. In majority of cases the differences between the two time series are low, and in 88 % of cases they are not higher than 40 %. The differences between the two become important during particularmenvironmental conditions, in general associated to the occurrence of particularly strong north-easterly (Bora) winds. It is well known that in such circumstances the wave motion generates resuspension of the bottom sediments, and causes erosion of the littoral adjacent to the Lido inlet. For the low wind conditions, the differences may occur during the ebb tidal flow of more than 0.5 m/s. The estimates of the sediment transport close to the bottom, which is predominantly constituted by fine and very fine sand, as demonstrated by recent investigations, significantly contributes to the accuracy of the fixed instrument time series. The future work will be focused on the integration of both contributes in the water column. This is fundamental in order to obtain an overall balance between the erosion and deposition in the Lido inlet.

The management of major renal trauma is still controversial and there are few studies about preservation of renal function after surgical reconstruction. We report our results on 10 patients who underwent renal reconstruction and quantitative assessment of differential renal function by radionuclide scintigraphy (99m-TC DMSA); mean follow-up was 6.6 years. Function was 25% or more in 9 reconstructed kidneys: this value is considered an adequate preservation of renal function. We consider reconstructive surgery an appropriate method to manage major renal injuries.

The backscatter signal recorded by the ADCP ('Acoustic Doppler Current Profiler'), and properly calibrated, has provided an estimation of the time variability of the suspended particulate matter (SPM) in the Malamocco inlet. Both the data from the ship-mounted ADCP and gravimetric data deriving from the water samples, collected during the campaign in January 2006, were used to determine the sediment concentration in the water column, above the bottom mounted ADCP, moored in the central part near the mouth of the inlet. Assuming that the relationship between the backscatter and the SPM concentration can be extended to a longer period, the calibration procedure was extrapolated for the time before and after the January campaign. Thus, the long term variability of the SPM concentration was obtained for the duration of four months (October 24, 2005 - February 21, 2006)., at the temporal and spatial resolutions of 10 minutes and 1 m, respectively. The evolution of a vertically averaged SPM concentration in the water column is depicted in Fig. 1, together with the vertically averaged axial current, and wind vector components. The currents are to a great extent tidally driven, with a prevalent semi-diurnal signal, whose range is modulated by a spring-neap cycle. Other long-term, non-tidal phenomena are of less influence. The concentration, on the contrary, shows a greater variability associated to the periods of strong winds, than to the tidal excursion. The wind influence plays a major role through the erosion induced by the waves. As observed, the analysed period is rich in strong wind events, particularly due to the bora (ENE wind). An additional aim of this study is to estimate the total SPM transport in the period of time across the inlet, on one hand, and, on the other hand, to derive a preliminary budget of the transport, in comparison with the other two inlets, Lido and Chioggia.

The fusion of data from the various screening modalities will lead to a cost effective breast cancer detection system that is certain to improve the early part of early breast cancer detection methods. We explore the integration of data from mammography, ultrasound, clinical evaluation, and CAD, with noninvasive digital infrared imaging data from the BreastScan IR system, to improve early diagnosis. This will address a new solution to the screening of young women and women with dense breasts.

This article describes the strategies and the instruments applied in the development and implementation of a system aimed at assuring the production of food which is neither made of nor derived from genetically modified raw material in a confectionery firm. It was chosen to develop a specific planning method partially taken from HACCP and FMEA techniques, mainly as far as the systematic and rigorous analysis of risks is concerned (in this case, the contamination of raw material and/or their genetically modified derivatives along the food chain). The result is a management system model that food organizations can use to assure the traceability of all ingredients incorporated into their food products and, in the same time, to guarantee that these ingredients do not contain or consist or derive from genetically modified organisms (GMOs).

Infrared imaging of the breast has been primarily hampered by the many factors inherent in its technology. With the use of computer automated digital infrared technology, problems with subjectivity, reproducibility and spatial localization have been eliminated. The digital infrared imaging (DII) discussed herein has 99% detection sensitivity in a study of 109 tissue proven cases of breast cancer. Its sensitivity has been successfully demonstrated in lesions as small as 4 mm. Additionally, DII, can now be used in the clinical monitoring of localized breast cancer to access therapeutic response. In conjunction with mammography and ultrasound, DII can be utilized in the early detection of breast cancer.

Acute urine retention can be the first clinical sign of a rabdomyosarcoma (RMS) of bladder and prostate. This is particularly evident in the age group comprised between 2 and 4 years. The Authors report their experience on three cases of 2 years old males admitted for acute urine retention. One case was diagnosed to have an prostate RMS, the other two a RMS of the bladder. The prostate RMS refused the operation dying 2 years after operation. Of the two cases of RMS of the bladder, one was treated successfully by polychemotherapy treatment, the second, after polychemotherapy underwent a partial cystectomy. The Authors conclude affirming the importance of a ultrasonography of the lower urinary tract in all patients with acute retention of urine, since this could be the first sign of a RMS of prostate or bladder.

Retroperitoneal fibrosis (RF) often presents with characteristic clinical and urographic findings that may hide lymphoma. A case of RF with bioptic confirmation is reported. On CT examination the variations in enhancement were not useful in distinguishing RF from lymphoma. Although on sagittal and coronal images MR accurately depicted the extent of the abnormal retroperitoneal mass as found at surgery, it was not able to correlate heterogeneous low intensity T2-weighted signals with definitive histological features.

We report four cases of vaginal recurrence after cystectomy for bladder cancer. Vaginal recurrences are relatively rare and patients who have undergone previous surgery and radiation to pelvic organs, or patients with tumour of the bladder neck and urethra appear to be at high risk. It is very important to know the predisposing factors in order to adopt appropriate surgical therapy.

Almost 15 centuries ago, people fleeing civil disorder and barbarian invasions after the collapse of the Roman Empire began building houses on low-lying islands in the middle of a lagoon. These islands later on—in the 10th century—became the city of Venice, the center of the long-lived Venetian Republic. Surrounded by water, the republic flourished for more than 7 centuries thanks to its strategic position. It fell into decline only at the end of the eighteenth century after being occupied by Napoleon. The early Venetians who built their city on the water to defend it from attacks would never have expected that the water would become the city's most dangerous enemy. In fact, this is what has been going on during the last century Venice risks being destroyed by the very waters that once served as its defense.

Predictive factors of venous obstructions after implantation of a permanent pacemaker {#article-title-2} In our study, the reasons have been searched for predictive factors of venous obstruction that can occur after implantation of pacemakers to the patients with permanent pacemakers. Totally 166 patients were included to the study. Patients were divided into two groups according to percentage of stenosis (stenosis 0.05). Considering the type of device, in patients with an implanted PM, the group AE was 16% of the population, instead in patients with ICD or CRT was, respectively, 5.5 and 2.2% ( P < 0002). Conclusion The only independent and significant predictor for predicting the risk of adverse events was the type of leads and device implanted. This result is likely to be related to increased structural fragility of the leads, resulting in a higher incidence of fracture during the extraction. # Pacemakers in paediatrics: are they small adults? {#article-title-4} Paediatric patients are unique with unique indications and requirement for pacemakers. The presence of anatomical and functional abnormalities in this particular age group mandates special consideration to their needs and requirements. They differ from an adult population in many aspects, namely generator types, leads, route of implantation, and programmed setting. In addition, many patients with congenital heart disease are more vulnerable for complete heart block that needs special attention during implantation and afterward, psychosocial issues have a great impact on the outcome which requires personalized care from implantation through long-term follow-up. In this presentation, we try to address the issues related to pacemaker implantation in paediatric age group, with special emphases on patients with congenital heart disease, and to highlight the importance of multidisciplinary health care for device implantations. # Short-term procedural complications of implanting cardiac rhythm devices in haemodialysis patients {#article-title-5} Background and objectives Patients on haemodialysis present unique challenges to cardiac rhythm device implantation (CRDI). Chronic renal failure and dialysis may predispose patients to complications from implantation of pacemakers and defibrillators, counteracting the benefits. Methods All dialysis patients who underwent CRDI at a single-centre between 1995 and 2010 were included in the study. We identified 99 patients who underwent 121 CRDI procedures and analysed for complications occurring within 30 days of implantation. Results Among 99 patients, there were 57 men (57%), mean age 72.8 ± 11.6 years. Implantable cardioverter defibrillators were implanted in 60 and 40% received pacemakers. Of the 121 procedures, 11 complications (9%) were observed. Procedural complications, n (%): pneumothorax 1 (0.8%), pocket haematoma requiring evacuation 5 (4.1%), pocket infection requiring removal 2 (1.6%), Ipsilateral venous thrombosis 3 (2.5%). Conclusions Short-term complications are common in dialysis patients, which may impact the cost-effectiveness of device therapy in this population, but the benefits of CRDI outweigh the risks. Additional prophylactic steps may prevent complications in these patients and warrants further study. # Remote monitoring for non-ICD pacemakers: should we now implant and forget after 6 months? {#article-title-6} Background Remote monitoring (RM) is considered standard of care for CIED surveillance. Clinic workload should be attenuated, not increased by this technology. With RMs proven utility for monitoring complex devices, it may be possible to abrogate clinic follow-up for simpler devices. We analysed RM notifications following activation, focused on the initial 6 months. Methods Remote monitoring was established at our hospital in 2007, and appropriate clinical algorithms established. Event notifications in the first 6 months were analysed for the BiotronikCardioMessenger® (CM) wireless system. Other systems were not included due to smaller numbers. Of 76 CM capable devices implanted, 20 patients declined monitoring or died. Events were classified: (i) minor–not requiring other than routine surveillance; (ii) major—requiring direct contact or unscheduled review in clinic; (iii) critical—requiring immediate intervention and/or admission to hospital. Results In the first 6 months of surveillance for enabled devices, only 76 minor events were notified among 12 patients in the non-ICD group. One major event was logged. HM detected inappropriate atrial lead sensing leading to recall and lead revision. No critical events occurred. No missed events were detected in clinics. Beyond 6 months, event notifications remained low or negligible. Conclusion Our experience suggests that significant events are rare in the first 6 months post implant, and are likely to remain so beyond this period. With the proven safety and reliability of the CM system in clinical trials, elimination or expansion of follow-up for simpler devices until near ERI seems justified. # Predictive parameters for a specific technique utilization in endovascular lead extraction {#article-title-7} Background The percentage of PM leads functioning properly after 10 years is ∼72%, while the percentage for ICD leads after 8 years is ∼60%. The incidence of lead infections was estimated to be between 0.5 and 12.6%. Different techniques and approaches ensure a success between 90 and 98%, with rare complications (1–3%). The actual extraction techniques included manual traction, manual traction by locking stylets, mechanical extractors, electrosurgical dissection sheath and laser using a femoral, jugular, subclavian, or hybrid approach. Aim Investigate the existence of predicting variables for lead extraction success. Methods From April 2003 to October 2010, 618 patients were subjected to lead extraction procedures (M 76%, F 24%, 68.4 ± 13 years). The number of extracted leads was 1160, 9% single-coil (SC) with passive fixation (PF), 5.2% SC with active fixation (AF), 10.7% double-coil (DC) with PF, 12.6% DC with AF, 22.2% ventricular stimulation leads with PF, 5.9% ventricular stimulation lead with AF, 27.9% atrial stimulation leads with PF, 5.3% atrial stimulation leads with AF, 10.9% coronary sinus leads, and 0.3% VDD (lead age 120 months). Results Success was achieved in 94% out of 1160 extracted leads. The mean age of leads extracted with laser was 259.8 ± 165.4 months; for the leads extracted with other methods was 115.9 ± 100.9 months ( P < 0.01). Conclusion The only independent predictor for the use of laser technique for extraction was the age of the catheter: every month over, the probability of using a laser increases by 1% (10% for year of the catheter).

A group of 24 imidazo[1,2-c]pyrimidines was taken into consideration in order to study their relationships between chemical structure and antiinflammatory activity. Some of these compounds were synthesized by us in the past, the others have been synthesized and characterized to complete the series. Antiinflammatory, analgesic, antipyretic and gastric ulcerogenic activities of such compounds were compared with those of indomethacin and discussed in terms of the effects exerted by the presence on the heterocyclic system of various substituents and an acidic or nonacidic moiety.

Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT) expression has been immunohistochemically investigated in 112 formalin-fixed paraffin-embedded surgical gastric samples, 38 of which were early carcinomas (EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data (ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa) were also analysed; in addition, 22 biopsies of normal gastric mucosa were studied as tissue control. The MT immunoreactivity was evaluated by staining and intensity-distribution scores. A various MT positivity was appreciable in the cytoplasm and nucleus of antrum or body gastric epithelial cells in 100% of normal control biopsies. 75/112 (67%) gastric carcinomas showed MT immunoreactivity with a significant lower expression in AGC. No relationships were encountered between MT immunostaining and clinico-pathological data; in addition, no difference in the Kaplan-Meier survival curves of patients with various MT expression was achieved. When the transitional mucosa was examined, 84/89 (94%) samples were stained although the immunoreaction was not always concordant with that encountered in adjacent carcinomatous elements. The significant statistical decrease of MT scores observed by us moving from normal to neoplastic gastric mucosa allows us to exclude the hypothesis of an overexpression of MT in gastric carcinomas.

METHODS—A large family is described in which mental retardation segregates as an X linked trait. Six affected males in three generations were studied by linkage and clinical examination. RESULTS—Characteristic clinical features include short stature, prominent lower lip, small testes, muscle wasting of the lower legs, kyphosis, joint hyperextensibility, abnormal gait, tremor, and decreased fine motor coordination. Affected subjects also had impaired speech and decreased attention span. A carrier female was mildly affected. A similar disorder was not found on review of our XLMR Database of 124 syndromes. Linkage analysis of 37 markers resulted in a lod score of 2.80 at DXS1212 and 2.76 at DXS425. The limiting markers were DXS424 and DXS1047. Ten of 124 XLMR syndromes and eight of 58 MRX families overlap this region. CONCLUSIONS—In summary, this family appears to have a new XLMR syndrome localising to Xq24-q25. Keywords: X linked mental retardation; Xq24-q25; syndrome

In the last 100 year, many progresses have been done in the ileal urinary diversion after cystectomy. Although the interest for the continent urinary diversion has increased enormously in the last ten years, the ileal conduit still represents the golden standard. We report our experience.

Fe/ZSM-5 catalysts prepared by CVD (chemical vapor deposition) show a stable activity in the selective catalytic reduction of N2O and NO with propane in the off-gas from chemical processes. These catalysts show a better propane economy and a considerable higher resistance to deactivation by SO2 especially at lower reaction temperatures than using Fe/ZSM-5 catalysts prepared by ion-exchange or impregnation, especially when the parent zeolite is pretreated to create structural defects. The peculiar activity and stability characteristics of these catalysts are suggested to be related to the presence of iron-oxide nanocluster, whereas with other methods highly clustered Fe3+ species and Fe2O3 particles also form.

Mc Kusick-Kaufman Syndrome (SMK) is an autosomal recessive multiple malformation Syndrome characterized by hydrometrocolpos and polydactyly. This Syndrome is more frequent in females, whose parents are first-degree cousins (frequency 1:8 liveborn). We describe two cases of SMK: a male and a female. Patients were siblings and their parents were first cousins. The first child presented postaxial hexadactily, of the hands and feet, cardiovascular malformation and Arnold-Chiari II malformation. The baby died on the 17th day of life, for neurosurgical complications. Second baby, in which a prenatal ultrasonography showed a large cystic dilatation in the pelvis, presented with urinary hydrometrocolpos associated with persistent urogenital sinus (UGS) and polydactyly. The patient was temporary treated with intermittent vaginal catheterization. At age of 6 months she underwent reconstructive surgery via the anterior sagittal transanorectal approach (ASTRA), previous creation of a colostomy. Thirty-two months of the operation, the patient is continent for stool and urine and the vagina looks normal.

To define the neonatal management and ultimate surgical correction via the anterior sagittal transanorectal approach (ASTRA) in cases of neonatal urinary hydrometrocolpos associated with a persistent urogenital sinus (UGS).We report three patients with UGS (with no ambiguous genitalia) and urinary hydrometrocolpos in whom prenatal ultrasonography showed cystic dilatation of the pelvis. Two patients were temporarily treated with intermittent vaginal catheterization and antibiotic prophylaxis, and in one a cystostomy was necessary to temporarily drain the urine. At the age of 6-8 months the patients underwent reconstructive surgery of the UGS via the ASTRA, under a previous protective colostomy.The mean (range) age of the patients at the last follow-up was 18.7 (8-32) months. A good cosmetic result was obtained in all patients. The vagina was dilated briefly with no anaesthesia in each patient. Patients had normal faecal control after the colostomy was closed and none had urinary incontinence.When possible, intermittent vaginal catheterization permits sufficient temporary drainage of the urinary hydrometrocolpos associated with a persistent UGS. Subsequent ASTRA allows good exposure of the UGS, assuring the preservation of the anorectal innervation and of the sphincteric mechanism.

We identified a family with three males in two generations with moderate mental retardation. The two oldest were first cousins whose mothers were sisters. The third affected was a grandson through a daughter of one of the sisters, strongly suggesting X- linked inheritance. The affected males had prominent glabella, synophrys, prognathism, generalized hirsutism, and bilateral single palmar creases. All developed seizures in childhood. The two oldest have had a slow deterioration in neurological status with poor gait and balance and progressive weakness. No deterioration in their mental status has been observed. The oldest had cerebellar atrophy confirmed on computed tomography and magnetic resonance imaging scans of the brain and prolonged nerve conduction velocity. Two of the males had hypogammaglobulinemia (IgA deficient). Two-point linkage analysis using 27 microsatellite markers on the X chromosome resulted in a maximum LOD score of 2.23 at straight theta = 0 for locus DSX101. Recombination was observed at locus DSX1170 in Xq21.33 and locus DXS8067 in Xq23. We conclude that this family represents an X-linked disorder associated with a recognizable phenotype, progressive neurological deterioration, and variable hypogammaglobulinemia. The gene appears to lie between Xq21.33 and Xq23.

We report on a family with severe X-linked mental retardation (XLMR) and progressive, severe central nervous system deterioration. Three of the five affected males died of secondary complications before the age of 10 years and none have survived past the age of 10. These complications included swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections. In addition, hypotonia and a mild myopathy were also present. All had a characteristic facies, including downslanting palpebral fissures, hypertelorism, and a short nose with a low nasal bridge. The two older boys showed cerebral atrophy by CT. No metabolic abnormalities were identified. Three obligate carriers had an IQ less than 80. The causal gene has been localized distal to DXS8103 in Xq28, a region spanning 5cM. No other XLMR disorder with these manifestations have been localized to this region and this appears to be a new disorder.

Of the gene-rich regions of the human genome, Xq28 is the most densely mapped. Mutations of genes in this band are responsible for 10 syndromal forms of mental retardation and 5 nonsyndromal forms. Clinical and molecular studies reported here add an additional syndromic form of X-linked mental retardation (XLMR) to this region. The condition comprises short stature, small hands and feet, seizures, cleft palate, and glaucoma. One affected male died at age 19 years in status epilepticus, but others have survived to old age. Carrier females do not have somatic anomalies or mental impairment. The gene is localized to the terminal 8 Mb of Xq28 with markers distal to DXS8011 showing linkage to the disorder with a lod score of 2.11 at zero recombination.

We studied a family with 11 males having X-linked mental retardation (XLMR) using microsatellite markers. Aside from the mental retardation, the affected males do not appear to differ from their unaffected brothers or uncles. The gene for this XLMR condition has been linked to DXS451 in Xp22.13 with a lod score of 5.18 at straight theta = 0. Recombination was detected at DXS992 (Xp21.3) and DXS1053 (Xp22.2), thereby defining the limits of the localization. This family is considered to have nonsyndromic XLMR and has been assigned the designation MRX32.