Developmental trajectory and sex differences in auditory processing in a PTEN-deletion model of autism spectrum disorders.

Autism Spectrum Disorders (ASD) encompass a wide array of debilitating symptoms, including severe sensory deficits and abnormal language development. Sensory deficits early in development may lead to broader symptomatology in adolescents and adults. The mechanistic links between ASD risk genes, sensory processing and language impairment are unclear. There is also a sex bias in ASD diagnosis and symptomatology. The current study aims to identify the developmental trajectory and genotype- and sex-dependent differences in auditory sensitivity and temporal processing in a Pten-deletion (phosphatase and tensin homolog missing on chromosome 10) mouse model of ASD. Auditory temporal processing is crucial for speech recognition and language development and deficits will cause language impairments. However, very little is known about the development of temporal processing in ASD animal models, and if there are sex differences. To address this major gap, we recorded epidural electroencephalography (EEG) signals from the frontal (FC) and auditory (AC) cortex in developing and adult Nse-cre PTEN mice, in which Pten is deleted in specific cortical layers (layers III-V) (PTEN conditional knock-out (cKO). We quantified resting EEG spectral power distribution, auditory event related potentials (ERP) and temporal processing from awake and freely moving male and female mice. Temporal processing is measured using a gap-in-noise-ASSR (auditory steady state response) stimulus paradigm. The experimental manipulation of gap duration and modulation depth allows us to measure cortical entrainment to rapid gaps in sounds. Temporal processing was quantified using inter-trial phase clustering (ITPC) values that account for phase consistency across trials. The results show genotype differences in resting power distribution in PTEN cKO mice throughout development. Male and female cKO mice have significantly increased beta power but decreased high frequency oscillations in the AC and FC. Both male and female PTEN cKO mice show diminished ITPC in their gap-ASSR responses in the AC and FC compared to control mice. Overall, deficits become more prominent in adult (p60) mice, with cKO mice having significantly increased sound evoked power and decreased ITPC compared to controls. While both male and female cKO mice demonstrated severe temporal processing deficits across development, female cKO mice showed increased hypersensitivity compared to males, reflected as increased N1 and P2 amplitudes. These data identify a number of novel sensory processing deficits in a PTEN-ASD mouse model that are present from an early age. Abnormal temporal processing and hypersensitive responses may contribute to abnormal development of language function in ASD.

Female-specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and estrogen receptor α.

Little is known of the brain mechanisms that mediate sex-specific autism symptoms. Here, we demonstrate that deletion of the autism spectrum disorder (ASD)-risk gene, Pten, in neocortical pyramidal neurons (NSEPten knockout [KO]) results in robust cortical circuit hyperexcitability selectively in female mice observed as prolonged spontaneous persistent activity states. Circuit hyperexcitability in females is mediated by metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) signaling to mitogen-activated protein kinases (Erk1/2) and de novo protein synthesis. Pten KO layer 5 neurons have a female-specific increase in mGluR5 and mGluR5-dependent protein synthesis. Furthermore, mGluR5-ERα complexes are generally elevated in female cortices, and genetic reduction of ERα rescues enhanced circuit excitability, protein synthesis, and neuron size selectively in NSEPten KO females. Female NSEPten KO mice display deficits in sensory processing and social behaviors as well as mGluR5-dependent seizures. These results reveal mechanisms by which sex and a high-confidence ASD-risk gene interact to affect brain function and behavior.

Female specific dysfunction of sensory neocortical circuits in a mouse model of autism mediated by mGluR5 and Estrogen Receptor α.

Autism manifests differently in males and females and the brain mechanisms that mediate these sex-dependent differences are unknown. Here, we demonstrate that deletion of the ASD-risk gene, Pten, in neocortical pyramidal neurons (NSE Pten KO) results in robust hyperexcitability of local neocortical circuits in female, but not male, mice, observed as prolonged, spontaneous persistent activity states (UP states). Circuit hyperexcitability in NSE Pten KO mice is mediated by enhanced and/or altered signaling of metabotropic glutamate receptor 5 (mGluR5) and estrogen receptor α (ERα) to ERK and protein synthesis selectively in Pten deleted female neurons. In support of this idea, Pten deleted Layer 5 cortical neurons have female-specific increases in mGluR5 and mGluR5-driven protein synthesis. In addition, mGluR5-ERα complexes are elevated in female cortex and genetic reduction of ERα in Pten KO cortical neurons rescues circuit excitability, protein synthesis and enlarged neurons selectively in females. Abnormal timing and hyperexcitability of neocortical circuits in female NSE Pten KO mice are associated with deficits in temporal processing of sensory stimuli and social behaviors as well as mGluR5-dependent seizures. Female-specific cortical hyperexcitability and mGluR5-dependent seizures are also observed in a human disease relevant mouse model, germline Pten +/- mice. Our results reveal molecular mechanisms by which sex and a high impact ASD-risk gene interact to affect brain function and behavior.

Nicotine reduces age-related changes in cortical neural oscillations without affecting auditory brainstem responses.

Neural oscillations at specific frequency bands are associated with cognitive functions and can identify abnormalities in cortical dynamics. In this study, we analyzed EEG signals recorded from auditory and frontal cortex of awake mice across young, middle and old ages, and found multiple robust and novel age-related changes in cortical oscillations. Notably, resting, evoked, and induced gamma power diminished with age, with some changes observed even in the middle age groups. Inter-trial phase coherence of responses to time-varying stimuli is reduced in old mice. Movement-related modulation of gamma power is reduced in old mice. An acute injection of nicotine (0.5 mg/kg), but not saline, in old mice partially or fully reversed the age-related changes in EEG responses. Nicotine had no effect on auditory brainstem responses , suggesting the effects occur more centrally. The age-related changes are consistent with reduced activation of specific inhibitory interneuron subtypes. Importantly, our data suggest that the auditory circuits that generate 'young' responses to sounds are present in old mice, and can be activated by nicotine.

Prevalencia de paperas en Bagdad. Irak - 2015 y 2016 / Prevalence of Mumps in Baghdad, Iraq - 2015 & 2016

Antecedentes: las paperas son una infección viral que se transmite por contacto directo, gotitas y fómites. Irak es testigo de varias epidemias de paperas. Objetivo: Informar sobre la última epidemia de paperas 2015-2016. Métodos: El lado de Bagdad de Al-Rusafa fue seleccionado al azar de dos lados de Bagdad. Se llevó a cabo una revisión de los datos del Departamento de Salud Pública de la Dirección de Salud de Bagdad / Al-Rusafa. Los datos fueron todos los casos notificados de paperas para los años 2015-2016. Resultados: Los casos registrados de paperas fueron 9780 y 33728 para 2015 y 2016, respectivamente. La edad máxima en 2015 y 2016 fue de 5 a 14 años. Los picos de casos de paperas se registraron en octubre, diciembre de 2015 y enero de 2016, y desaparecieron en junio de 2016. Conclusiones: La epidemia de paperas fue clara en Bagdad. La lucha social juega un papel en el desarrollo de la epidemia.

Background: Mumps is a viral infection transmitted by direct contact, droplet infection and fomites. Iraq witnesses several epidemics of mumps. Objective: To report on last epidemic of mumps 2015- 2016. Methods: Al-Rusafa side of Baghdad was selected randomly from two sides of Baghdad. A review of data from department of public health, Directorate of Health of Baghdad / Al-Rusafa was carried out. The data was all the notification cases of mumps for the years 2015-2016. Results: The registered cases of mumps were 9780 and 33728 for 2015 and 2016, respectively. The peak age in 2015 and 2016 was 5-14 year. The peaks mumps cases were in October, December 2015 and January 2016, and disappear in June 2016. Conclusions: Epidemic of mumps was clear in Baghdad. Social strife plays a role in developing the epidemic.

Punicalagin and zinc (II) ions inhibit the activity of SARS-CoV-2 3CL-protease in vitro.

OBJECTIVE: Coronavirus 2019 (COVID-19) has now been declared as a worldwide pandemic. Currently, no drugs have been endorsed for its treatment; in this manner, a pressing need has been developed for any antiviral drugs that will treat COVID-19. Coronaviruses require the SARS-CoV-2 3CL-Protease (3CL-protease) for cleavage of its polyprotein to yield a single useful protein and assume a basic role in the disease progression. In this study, we demonstrated that punicalagin, the fundamental active element of pomegranate in addition to the combination of punicalagin with zinc (Zn) II, appear to show powerful inhibitory activity against SARS-CoV-2. MATERIALS AND METHODS: The 3CL protease assay kit was used to quantify 3CL protease action. The tetrazolium dye, MTS, was used to evaluate cytotoxicity. RESULTS: Punicalagin showed inhibitory action against the 3CL-protease in a dose-dependent manner, and IC50 was found to be 6.192 µg/ml for punicalagin. Punicalagin (10 µg/mL) demonstrated a significant inhibitory activity toward 3CL-protease activity (p < 0.001), yet when punicalagin is combined with zinc sulfate monohydrate (punicalagin/Zn-II) extremely strong 3CL-protease activity (p < 0.001) was obtained. The action of 3CL-protease with punicalagin/Zn-II was decreased by approximately 4.4-fold in contrast to only punicalagin (10 µg/mL). Likewise, we did not notice any significant cytotoxicity caused by punicalagin, Zn-II, or punicalagin/Zn-II. CONCLUSIONS: We suggest that these compounds could be used as potential antiviral drugs against COVID-19.

Displaced intracapsular neck of femur fractures: Outcome of 810 hydroxyapetite coated (HAC) uncemented hemiarthroplasties.

A Cochrane review influenced new NICE guidelines, which recommended surgeons: Offer cemented implants to patients undergoing surgery with arthroplasty. However our trust routinely uses HAC uncemented stem (Taperloc®, Biomet) hemiarthroplasties. A review of a consecutive series of uncemented HAC stem hemiarthroplasties including measures such as intro-operative complications, mortality and revision surgery. Prospectively collected data between January 2008 and June 2014 was used, with medical record and radiographic reviews performed. 810 consecutive Taperloc uncemented hemiarthroplasty with monopolar heads were performed in 763 patients, with a minimum 12 month follow-up (12-90) follow-up. Mean age 83yrs; 71% female. Meantime to operation was 28.5h. 30day mortality: 4.4% (33/763). One year mortality was 11.2% (89/763). 2.5% (20/810) were admitted on a separate admission with the periprosthetic fracture. 0.6% (5/810) were revised to total hip replacement for subsidence and associated pain. Only 1% (8/810) had intraoperative calcar fractures, all of which were treated with intraoperative cabling with no evidence of clinically relevant subsidence or medium term complications requiring revision surgery within a year. To the author's knowledge this is largest outcome series for modern design uncemented hemiarthroplasty. Our study shows comparable data to cemented hemiarthroplasty but no deaths in the first 2days post-op. Our series also demonstrates a well below average mortality figures which are clearly multifactorial but believe uncemented prosthesis play a role. We believe that uncemented proven stem design hemiarthroplasty remains a safe and good surgical option for displaced intracapsular fractures.

Preparation of Chito-Oligomers by Hydrolysis of Chitosan in the Presence of Zeolite as Adsorbent.

An increasing interest has recently been shown to use chitin/chitosan oligomers (chito-oligomers) in medicine and food fields because they are not only water-soluble, nontoxic, and biocompatible materials, but they also exhibit numerous biological properties, including antibacterial, antifungal, and antitumor activities, as well as immuno-enhancing effects on animals. Conventional depolymerization methods of chitosan to chito-oligomers are either chemical by acid-hydrolysis under harsh conditions or by enzymatic degradation. In this work, hydrolysis of chitosan to chito-oligomers has been achieved by applying adsorption-separation technique using diluted HCl in the presence of different types of zeolite as adsorbents. The chito-oligomers were retrieved from adsorbents and characterized by differential scanning calorimetry (DSC), liquid chromatography/mass spectroscopy (LC/MS), and ninhydrin test.

The arcuate ligament revisited: role of the posterolateral structures in providing static stability in the knee joint.

PURPOSE: To determine the involvement of the posterolateral structures including the lateral collateral ligament, the popliteus muscle-tendon unit, the arcuate ligament (popliteofibular ligament, fabellofibular ligament, popliteomeniscal fascicles, capsular arm of short head of the biceps femoris and anterolateral ligament) and the posterior cruciate ligament in providing restraint to excessive recurvatum, tibial posterior translation and external tibial rotation at 90° of flexion. METHODS: Ten fresh-frozen cadaveric knees were tested with dial test, posterior drawer test and recurvatum test. The values were collected, using a surgical navigation system, on intact knees, following a serial section of the posterolateral corner (lateral collateral ligament, arcuate ligament and popliteus muscle-tendon unit), followed by the additional section of the posterior cruciate ligament. RESULTS: The mean tibial external rotation, recurvatum and posterior drawer were, respectively, measured at 9° ± 4°, 2° ± 3° and 9 ± 1 mm on intact knees. These values increase to 12° ± 5°, 3° ± 2° and 9 ± 1 mm after cutting the lateral collateral ligament; 17° ± 6° (p < 0.05), 3° ± 2° and 10 ± 1 mm after sectioning the arcuate ligament; 18° ± 7°, 3° ± 2° and 10 ± 1 mm after sectioning the popliteus muscle-tendon unit and 27° ± 6° (p < 0.05), 5° ± 3° (p < 0.05) and 28 ± 2 mm (p < 0.05) after the additional section of the posterior cruciate ligament. CONCLUSION: Among the different structures of the posterolateral corner, only the arcuate ligament has a significant role in restricting excessive primary and coupled external rotation. The popliteus muscle-tendon unit is not a primary static stabilizer to tibial external rotation at 90° of knee flexion. The posterior cruciate ligament is the primary restraint to excessive recurvatum and posterior tibial translation. The posterior cruciate ligament and the arcuate ligament have predominant role for the posterolateral stability of the knee. The functional restoration of these ligaments is an important part of the surgical treatment of posterolateral ligamentous injuries.

Symptomatic secondary vesical calculus formed on an intrauterine contraceptive device inserted 25 years previously.

A 57-year-old postmenopausal woman presented with vague lower abdominal symptoms, dysuria and recurrent urinary tract infection of a year's duration. She had an intrauterine contraceptive device (IUCD) inserted 25 years previously and denied having any significant gynecological or urinary tract symptoms since the device was inserted. CT scan of her pelvis confirmed the presence of an IUCD that had migrated into the urinary bladder and on which a calculus had formed. An attempt at removal of the calculus and IUCD during cystoscopy failed. At cystolithotomy, the IUCD and the calculus were removed intact. IUCDs may produce complications several years after insertion.

A prospective trial comparing the Holland nail with the dynamic hip screw in the treatment of intertrochanteric fractures of the hip.

We compared the outcome of patients treated for an intertrochanteric fracture of the femoral neck with a locked, long intramedullary nail with those treated with a dynamic hip screw (DHS) in a prospective randomised study. Each patient who presented with an extra-capsular hip fracture was randomised to operative stabilisation with either a long intramedullary Holland nail or a DHS. We treated 92 patients with a Holland nail and 98 with a DHS. Pre-operative variables included the Mini Mental test score, patient mobility, fracture pattern and American Society of Anesthesiologists grading. Peri-operative variables were anaesthetic time, operating time, radiation time and blood loss. Post-operative variables were time to mobilising with a frame, wound infection, time to discharge, time to fracture union, and mortality. We found no significant difference in the pre-operative variables. The mean anaesthetic and operation times were shorter in the DHS group than in the Holland nail group (29.7 vs 40.4 minutes, p < 0.001; and 40.3 vs 54 minutes, p < 0.001, respectively). There was an increased mean blood loss within the DHS group versus the Holland nail group (160 ml vs 78 ml, respectively, p < 0.001). The mean time to mobilisation with a frame was shorter in the Holland nail group (DHS 4.3 days, Holland nail 3.6 days, p = 0.012). More patients needed a post-operative blood transfusion in the DHS group (23 vs seven, p = 0.003) and the mean radiation time was shorter in this group (DHS 0.9 minutes vs Holland nail 1.56 minutes, p < 0.001). The screw of the DHS cut out in two patients, one of whom underwent revision to a Holland nail. There were no revisions in the Holland nail group. All fractures in both groups were united when followed up after one year. We conclude that the DHS can be implanted more quickly and with less exposure to radiation than the Holland nail. However, the resultant blood loss and need for transfusion is greater. The Holland nail allows patients to mobilise faster and to a greater extent. We have therefore adopted the Holland nail as our preferred method of treating intertrochanteric fractures of the hip.

The transverse acetabular ligament may be used to align the acetabular cup in total hip arthroplasty.

Accurate positioning of the acetabular component in total hip arthroplasty is essential to minimise the risk of dislocation and preserve the range of movement of the hip. It also affects polyethylene wear and the rate of osteolysis. Although there are many tools available to the surgeon to aid placement of the acetabular component, errors still occur, especially in version. We conducted a study of 14 cadaveric hips to investigate whether the transverse acetabular ligament can be used to align implanted cups with the correct degree of anteversion. Radiographic measurement revealed that all of the implanted cups were found to lie within the 'safe zone' for anteversion, when aligned with the ligament.

Do differences in age specific androgenic steroid hormone levels account for differing prostate cancer rates between Arabs and Caucasians?

OBJECTIVE: Factors responsible for the low incidence of clinical prostate cancer in the Arab population remain unclear, but may be related to differences in androgenic steroid hormone metabolism between Arabs and other populations, especially as prostate cancer is believed to be androgen dependent. We therefore measured the levels of serum androgenic steroids and their binding proteins in Arab men and compared results obtained with values reported for Caucasian populations to determine if any differences could at least partially account for differences in incidence of prostate cancer rates between the two populations. METHODS: Venous blood samples were obtained from 327 unselected apparently healthy indigenous Arab men (Kuwaitis and Omanis) aged 15-79 years. Samples were also obtained from 30 Arab men with newly diagnosed prostate cancer. Serum levels of total testosterone (TT), sex hormone binding globulin (SHBG), derived free androgen index (FAI); adrenal C19 -steroids, dehydroepiandrosterone sulfate (DHEAS) and androstenedione (ADT) were determined by chemiluminescent immunoassay. Age specific reference intervals, mean and median for each analyte were determined. Frequency distribution pattern for each hormone was plotted. The reference range for hormones with normal distribution was mean +/- 2SD and 2.5-97.5% for those with non-normal distribution. The mean serum levels of the hormones in Arab men with prostate cancer were compared with values in healthy age-matched Arab men. RESULTS: There was a significant decrease between the 21-29 years age group and the 70-79 years age group for TT (-38.77%), DHEAS (-70%), ADT (-36%) and FAI (-63.25%), and an increase for SHBG (+64%). The calculated reference ranges are TT (2.73-30.45 nmol/L), SHBG (6.45-65.67 nmol/L), FAI (14.51-180.34), DHEAS (0.9-11.0 micromol/L) and ADT (0.54-4.26 ng/mL). The mean TT, SHBG, DHEAS and ADT in Arab men were significantly lower than those reported for Caucasians especially in the 21-29 years age group. Arab men with newly diagnosed prostate cancer had higher serum TT (P < 0.7), ADT (P < 0.2), SHBG (P < 0.2) and lower DHEAS (P < 0.008) compared to aged matched controls. CONCLUSIONS: Serum TT, SHBG, DHEAS and ADT levels are significantly lower in Arab men compared to those reported for Caucasian men, especially in early adulthood. Arab men with newly diagnosed prostate cancer have higher circulating androgens compared to healthy controls. We suggest that low circulating androgens and their adrenal precursors in Arab men when compared to Caucasians may partially account for the relatively lower risk for prostate cancer among Arab men.

Treatment of calculi in kidneys with congenital anomalies: an assessment of the efficacy of lithotripsy.

We studied the effectiveness of extracorporeal shock wave lithotripsy (ESWL) in the treatment of stones in kidneys with congenital anomalies to determine factors that may affect the results. Patients found to have renal calculi in kidneys with different types of congenital anomalies were treated using ESWL. All patients were investigated by intravenous urography (IVU) to confirm the diagnosis. J stents were inserted prior to therapy in renal units with calculi exceeding 1.5 cm in diameter. Complications encountered and factors affecting success using this treatment modality were analysed. Twenty-five patients (18 males, 7 females) were studied between August 1988 and July 2005. There were nine patients with horseshoe kidneys, eight with ectopic kidneys, three with malrotated kidneys, two with duplex renal system, and one patient each with polycystic kidneys and hypoplastic kidney. The IVU showed 31 isolated calyceal or renal pelvic stones with mean stone burden of 1.44cc. All 25 patients were treated by lithotripsy. Twenty-four (77.4%) renal units (in 19 patients) were completely cleared of stones, 2 (6.5%) renal units (2 patients) were partially cleared of calculi and the procedures failed in 5 (16.1%) renal units (4 patients). Out of five renal units in which the procedures failed, open surgery was performed in three renal units and percutaneous nephrolithotomy (PCNL) was performed in two. None of the 25 patients developed any major complications. No significant adverse changes in renal function tests were observed at 3-month follow-up. The stone-free rate was influenced and reduced by stone size and location in the pelvi-calyceal system. Calculi in kidneys with congenital anomalies may be treated successfully by ESWL as a first-line therapy in the majority of patients. With position modifications, localization of stones may be facilitated and disintegrated. The outcome in patients so treated does not differ significantly from that in those with normal kidneys.

Tension free vaginal tape versus Burch colposuspension for treatment of female stress urinary incontinence.

INTRODUCTION: Many surgical procedures have been proposed for treatment of stress urinary incontinence (SUI) but none of them has proved completely successful. The aim of this study is to compare the efficacy and safety of tension free vaginal tape (TVT) with Burch colposuspension in the treatment of SIU. PATIENTS AND METHODS: Fifty female patients, presenting with SUI were randomly divided into two equal groups. SUI was confirmed using urodynamic study in all patients. Group 1 (n=25) patients underwent Burch colposuspension while Group 2 (n=25) underwent TVT. Patients with high grade cystocele, previous surgical failure for SUI, uninhibited detrusor contraction during bladder filling on urodynamic study and incompetent internal sphincters were excluded from this study. A patient was declared cured of SUI, if 3-6 months after surgery she had no SUI. The procedure was judged to be a failure if 3-6 months after surgery, patient had SUI. RESULTS: In group 1 patients, 72% were completely cured, 16% improved and 12% showed no improvement. In group 2 patients, 72 were completely cured, 20% improved and only 8% showed no improvement. There was no difference between the two groups in terms of cure rates. Operative time for TVT was significantly less compared to Burch. Postoperative pain was less in TVT than Burch. Return to normal activity was earlier in TVT compared to Burch group. Intra operative perforation of the urinary bladder occurred in 8% of patients in group 2. Urine retention occurred in 12% of patients in group 1 compared to 20% in group 2. This was successfully managed conservatively. De novo urgency developed in 12% in group I and 8% in group II and was successfully managed by medical treatment. CONCLUSION: The success rates of TVT and Burch colposuspension in the treatment of SUI in our experience are very similar. However, TVT is associated with less morbidity. We recommend TVT procedure for females with genuine SUI.

Severe emphysematous pyelonephritis in diabetic patients: diagnosis and aspects of surgical management.

PURPOSE: Emphysematous pyelonephritis (EPN) is a rare, severe gas-forming infection of renal parenchyma and surrounding tissues seen mostly in diabetic patients. Diagnosis and adequate therapeutic regimen are controversial. We reviewed the clinical presentation, diagnosis and aspects of surgical management of patients presenting with severe EPN. PATIENTS AND METHODS: Patients with EPN managed in our unit between 1996 and 2004 were reviewed. Diagnosis was confirmed by CT scan appearance of gas in the renal or perirenal area in a very ill patient. We compared the outcome of immediate nephrectomy with drainage of perinephric abscesses in patients presenting with severe EPN. RESULTS: Seven patients were managed in our unit during the 8-year period. All patients were diabetic and women outnumbered men (6:1). Renogram in all 7 patients showed renal function of affected kidney to be less than 15% in 6 patients. Escherichia coli was isolated in all patients from either urine, blood or perinephric pus. Management consisted of intensive resuscitation, control of blood glucose and use of intravenous antibiotics. Emergency nephrectomy was performed in 3 patients, delayed nephrectomy after an initial period of percutaneous drainage in 2 patients, incision and drainage in one patient and immediate percutaneous drainage was performed in one patient. One patient died 5 days post-nephrectomy of myocardial infarction. Patients who had immediate nephrectomy recovered quicker (18-21 days) and had no postoperative complications. Patients who had incision and drainage, or percutaneous drainage presented with recurrent discharging sinuses or perinephric abscesses requiring further surgical interventions and spent longer time in hospital (28-37 days). CONCLUSION: Patients with severe EPN often present in extremis and require intensive medical treatment. The diagnosis must be entertained in diabetic women presenting with flank pain and septicemia. The function of the affected kidney is often very poor and early nephrectomy offers the best outcome. Percutaneous drainage or incision and drainage of the abscess may be performed in patients too ill for immediate formal nephrectomy.

Reference intervals for important serum sex steroid hormones, prostate-specific antigen, insulin-like growth factor-1 and IGF binding protein-3 concentration in a normal Kuwaiti adult male population.

OBJECTIVES: The purpose of this study was to determine the age-specific reference ranges for some important male sex steroid hormones, prostate-specific antigen (PSA), insulin-like growth factor-1 (IGF-1), and IGF binding protein-3 (IGFBP-3), for the Kuwaiti population. SUBJECTS AND METHODS: Blood samples were taken from 398 consenting, fasting, healthy Kuwaiti males aged 15-80 years between 8.00 a.m. and 12.00 noon. The serum concentrations of total testosterone (TT), dehydro-epiandrosterone sulfate (DHEAS), androstenedione (ADT), sex hormone binding globulin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), prolactin, PSA, IGF-1 and IGFBP-3 were determined. A distribution curve was plotted and age-specific reference levels were determined for each analyte. The reference interval for parameters with a normal distribution (Gaussian) was mean +/- 2 SD, while for the non-normal distribution (non-Gaussian), it was 2.5-97.5 percentile. The reference intervals for the analytes obtained from this study were compared with those suggested by the kit manufacturers and currently used by the Ministry of Health, Kuwait Laboratories (MOHKL). RESULTS: Serum IGFBP-3 and ADT had normal distribution while other analytes had non-normal distribution. The reference intervals from this study, manufacturers kit and MOHKL were as follows: TT 3-31, 9-60, 8-35 nmol/l; DHEAS 0.9-11, 1.0-7.3, 2.2- 15.2 micromol/l; ADT 0.5-4.3, 0.8-2.8, 2.0-9.2 nmol/l; LH 1-11, 0.8-7.6, 0.4-5.7 mIU/l; FSH 0.5-11, 0.7-11.1, 1.1-13.5 mIU/l; prolactin 42-397, 53-360, 80-230 nmol/l; IGF-1 41-542, 78-956, 71-261 ng/ml; IGFBP-3 88- 2,090, 900-4,000, 900-4,000 ng/ml, and PSA 0-3.1, 0-4, 0-4 ng/ml, respectively. CONCLUSION: These data indicate that for Kuwaitis lower reference ranges must be used for serum TT, DHEAS, ADT, IGFBP-3 and PSA. There is no need to change the currently used reference interval for FSH whereas higher values must be used for LH, prolactin, and IGF-1.

Fragility fractures of the ankle: stabilisation with an expandable calcaneotalotibial nail.

Fragility fractures of the ankle occur mainly in elderly osteoporotic women. They are inherently unstable and difficult to manage. There is a high incidence of complications with both non-operative and operative treatment. We treated 12 such fractures by closed reduction and stabilisation using a retrograde calcaneotalotibial expandable nail. The mean age of patients was 84 years (75 to 95). All were women and were able to walk fully weight-bearing after surgery. There were no wound complications. One patient died from a myocardial infarction 24 days after surgery. The 11 other patients were followed up for a mean of 67 weeks (39 to 104). All the fractures maintained satisfactory alignment and healed without delay. Six patients refused removal of the nail after union of the fracture. The functional rating using the scale of Olerud and Molander gave a mean score at follow-up of 61, compared with a pre-injury value of 70.