This case involved a 63-year-old woman with hypertension and hypothyroidism, who presented to her primary care physician with a complaint of worsening "clicking" in her left ear. Accompanying symptoms included dizziness and light-headedness. The "clicks" had been heard for several months and were thought to originate from the Eustachian tube. The dizziness had been present for several weeks and was consistent with vertigo, involving "whirling sensations" that were exacerbated by movement. Treatment of the vertigo with meclizine was unsuccessful. There were no complaints of decreased hearing, headache, or other neurological deficits. The patient was advised to follow up with a carotid duplex study and brain MRI.
Findings on the axial, contrast enhanced MRI were positive for a 18 × 14 × 13 mm enhancing mass at the left cerebellopontine angle. The lesion projected from the internal acoustic meatus, with a small intracanalicular tail. Slight compression of the pons, medulla, and left cerebellar hemisphere was noted. The presentation was radiographically consistent with an extracanalicular vestibular schwannoma, although there was the outlying possibility it was a meningioma. Referral was made to a neuro-otologist, and subsequent evaluation revealed normal cranial nerve functions, no nystagmus, and a normal Romberg test. Audiograms exhibited normal speech reception threshold, below 20 dB in both ears, and 100% speech discrimination scores bilaterally. The absence of symptoms related to cochlear nerve function is infrequently encountered with vestibular schwannomas, with fewer than 5% of patients presenting without hearing impairment[]. Cardiovascular exam was normal, with no abnormalities of jugular venous pressure or carotid pulse bilaterally.
Based on the images, the patient was diagnosed with vestibular schwannoma and counselled on the treatment options; conservative observation by serial MRIs, surgical removal, stereotactic radiotherapy, and gamma knife radiosurgery. Taking into account her age and health status, her neuro-otologist determined that suboccipital craniotomy was a treatment option with the potential for hearing preservation. The patient was informed of the risks associated with surgery including hearing loss, CSF leak, meningitis, facial nerve damage, and other complications. A radiation oncologist discussed the risks and benefits of Gamma Knife treatment, including reported recurrence rates and hearing preservation rates. Conservative management was discussed with several doctors, and one neurosurgeon recommended against it, given that the patient's primary motivation was hearing preservation. The patient also sought opinions from her primary care provider and an additional neurosurgeon.
After 4 months, meeting with various physicians and weighing the treatment options, the patient elected to pursue stereotactic radiosurgery. The preoperative gadolinium enhanced T1-MRI, required for Gamma Knife treatment planning, revealed the mass extending from the left acoustic meatus showing no significant expansion from the previous study (see Figure ). The tumour received a dose of 13 Gy prescribed to the 50% isodose line, which is slightly higher than the 12 Gy currently prescribed to our patients with VS. After tolerating the procedure and undergoing a brief period of observation, the patient was discharged to her home.
One month following treatment, the patient had no complaints. The minimal discomfort from the pin placement for the Gamma Knife frame had resolved in a matter of days. She noticed no change in hearing, facial movement, facial sensation, or balance. The first follow up MRI was taken at 9.5 months, revealing a 17 mm lesion, which was concluded to be a reduction in size upon direct comparison with the preoperative MRI. At 10 months there was no change in her symptoms, other than episodes of pain and popping, which was perceived in both ears. Imaging at 22 months revealed further decrease in all tumour dimensions, with no change in symptoms.
The patient's most recent follow up occurred 44.5 months following her Gamma Knife procedure. At that time, MRI showed a 15 mm tumour, which was visibly smaller that in the study two years prior (see Figure ). The patient did not comply with requests to obtain a follow up audiogram; however, she described no decrease in her hearing function. Symptoms of vertigo persisted, and she experienced a single brief episode of pain above the left auricle. Otherwise, there was no evidence for progressive cranial nerve disease or other complications, such as hydrocephalus or secondary malignancy. Overall, the tumour exhibited a stable appearance and reduction in size based on linear measurements. In addition to tumour control, her symptoms had not progressed, and therefore her Gamma Knife treatment was regarded as successful.
The recommended treatment for acoustic neuroma may depend on a number of factors; the tumour size, symptoms, patient age, and life expectancy. In practice, patients primarily choose observation, microsurgery, or radiosurgery, and the discipline of the attending physician is the greatest predictor of treatment choice[,]. This identifies the need for stronger evidence-based guidelines to reduce physician bias, necessitating more thorough comparison of the available interventions[]. With all modalities, the primary endpoint sought is tumour control. This is generally defined as prevention of additional growth. Secondary treatment goals include alleviating symptoms and minimizing complications. Traditionally, the predominant measure of such outcomes has been the preservation of hearing and facial nerve function; however, there is a desire to evaluate other measures of patients' experience and quality of life, including the symptoms of tinnitus, dizziness, and headache[]. This would provide patients a more complete picture to utilize in choosing a treatment strategy.
On average, vestibular schwannomas are slow growing; therefore, conservative management by periodic MRI is reasonable. In two large meta-analyses, the mean growth rate of tumours undergoing observation was determined to be 1.9 mm per year[,]. Unfortunately, the behaviour of an individual tumour is difficult to predict. Some may shrink spontaneously, while others may grow at rates 10 times that of the average tumour[]. Growth rates are not always constant, and even large data sets identify few predictive variables for future growth[]. The only indicators to this point are previous tumour growth, extracanalicular growth, and a younger age. A statistically significant (p < 0.01) difference in growth rates for intracanalicular and small tumours, compared to larger tumours of the cerebellopontine angle (CPA), was identified in two studies [,]. Larger tumours are more likely to grow and also grow faster. This intuitive result may be attributed to a greater number of proliferating cells, increased vascular perfusion, and greater spatial freedom for tumours of the CPA. The difficulty in predicting growth of VS is a risk patients undergoing observation must take into consideration.
The outcome for patients managed conservatively has been the subject of several reviews. Yamakami et al. reported that over a mean follow-up of 3.1 years, 51% of tumours grew, 20% eventually required intervention, and 37% of patients ultimately lost useful hearing (N = 903 patients)[]. In a meta-analysis by Smouha et al., 43% showed growth, 20% required treatment, and 51% of patients experienced hearing loss over a mean follow-up of 3.2 years (N = 1345 patients)[]. Myrseth et al. reviewed the literature and determined that over a 3 year period 30-50% of patients undergoing conservative management will lose useful hearing and 15-50% will ultimately require active treatment[]. Patients must be aware that a significant fraction managed conservatively will eventually require intervention or experience progression of symptoms.
The decision to undergo conservative management is not straightforward, although some treatment guidelines have been proposed. An algorithm designed by Smouha et al. recommends observation in elderly patients, with small tumours, and no symptoms other than hearing loss[]. They define elderly patients as over 45 years and small tumours as less than 25 mm in diameter. Upon observing growth beyond 2 mm/year or changes in symptoms, intervention is indicated. Unfortunately there is little correlation between symptoms and tumour size, and patient quality of life may diminish even without growth[]. Therefore, treatment may also be indicated when symptoms progress but the tumour size remains static. Concerns about patient compliance have also been voiced, and high attrition rates were noticed in some conservative management studies[]. Nonetheless, observation remains a practical choice for many patients.
Historically, surgical removal has been the standard for treating vestibular schwannomas. Surgical resection of a VS was first documented in 1894[]. Early on, mortality was above 50% until modern practices reduced that number to below 1%[]. Today, surgery remains complicated, but the surgical microscope and improved techniques offer excellent tumour control with significantly reduced morbidity and mortality[,]. Kaylie et al. reviewed data about surgical outcomes from the 1990's, including 2579 patients who underwent surgical removal of VS. Tumour control, measured as lack of recurrence, was achieved in greater than 98% of cases[]. In a similar analysis, Yamakami et al. reported 96% of tumours were completely removed, and only 1.8% recurred, following microsurgery in 5005 patients[]. For larger tumours, the efficacy of microsurgery is unmatched, and Nikolopoulos et al. report that for tumours larger than 3 cm "it would be unethical to treat other than by surgical removal."[].
Concerns about microsurgical intervention stem from the potential morbidities associated with intracranial procedures. Tumour size and surgeon's experience both play a role in the risks to the patient[]. Hearing loss is an obvious morbidity, and deafness reportedly occurs in 50% of patients, although long term follow-up data is lacking[]. Hearing preservation has been reported at very low rates with tumour sizes greater than 20 mm[]. Meta-analysis of the literature from the 1990's identified other complications in 21.9% of cases[]. The mortality rate was very low (0.3%) and CSF leak was the most common morbidity (10.95%). Other complications included facial nerve transection (3.9%), meningitis (1.2%), and damage to other cranial nerves (1.1%). A more recent review of the literature reports mortality in 0-2%, CSF leakage in 3-15%, facial nerve transection in 2.5-7%, and meningitis in 1-3%[]. Data is limited on the impact of surgery on tinnitus, vertigo, and balance. Despite improved techniques, significant risks do still exist with surgery. Some patients may desire less invasive intervention while others may not be surgical candidates at all because of comorbid conditions.
Stereotactic radiosurgery (SRS) is an accepted alternative to microsurgery for smaller tumours and non-surgical candidates, offering similar tumour control rates[,,,]. Meta analysis including studies from the 1990's identified an average tumour control rate of 91% with Gamma Knife radiosurgery[]. A more recent review identified a range of control rates, from 89-100% reported in various studies. Complicating the interpretation of such results, many of which report on patients first treated over a decade ago, is that Gamma Knife technology and treatment planning continues to undergo significant evolution. Improvements in imaging resolution and computer planning software, have allowed physicians to better spare adjacent brainstem and nerve structures[,]. Furthermore, the therapeutic dose used for treating VS has decreased over the past two decades, with marginal doses of 12 Gy and maximum doses of 20-25 Gy identified as current standards[]. Therefore, controlling vestibular schwannomas with fewer risks may be accomplished with contemporary SRS.
Patients treated with SRS can have a similar complication profile to those treated with intracranial surgery. Meta-analysis from early experience showed that 44% with serviceable hearing prior to treatment retained their ability after SRS, a statistically equivalent rate to the surgical data[]. This evidence also suggest that 37.9% of patients have other complications[]. Trigeminal neuropathy was experienced by 36%, 6% had facial nerve injury, and 1.9% developed hydrocephaly. Hearing loss following radiosurgery has been linked to dose margins overlapping the cochlea, or brainstem nuclei of the cochlear nerve[,]. Several studies indicate that lower doses and more precise planning software used currently, offer greater preservation of hearing and reduction of facial neuropathy compared to surgery[,,,,]. This was indicated in a recent review where hearing preservation rates range from 50-89% in more contemporary studies[]. The rates of other complications were 3-5% for trigeminal neuropathy, 1-4% for facial neuropathy, and 2-4% for hydrocephaly[]. With radiation exposure, there also remains a small risk of developing secondary neoplasm, but few studies of VS include follow-up times necessary to determine the true risks. Ultimately, the side effect profile for radiosurgery appears to be comparable to or slightly better than microsurgery.
Fractionated stereotactic radiotherapy (SRT) is an alternative use of radiation in the treatment of vestibular schwannoma. A review of available evidence suggests that SRT may offer even better hearing preservation and lower cranial nerve toxicity than SRS based on biologic models[]. This includes similar tumour control rates with hearing preservation greater than 90%. Unfortunately, being a newer therapy, there are not yet long-term comparative outcome studies to evaluate the relative efficacy of SRT compared to SRS or microsurgery [].


The patient was a 69-year-old Caucasian man without a history of mental illness or any previous psychiatric treatment. He was initially transferred to a medical emergency department with marked dyspnoeic symptoms and tachycardia, where an acute coronary syndrome was diagnosed. After laboratory testing and an electrocardiogram a non-ST elevation myocardial infarction (NSTEMI) was diagnosed. The following coronary angiography (an intervention that was endured by the patient with enormous dread), revealed severe three-vessel disease.
The patient was informed of the urgent indication of a bypass operation, which was planned as an emergency intervention on the same day. At the end of the angiographic intervention, this information caused a severe panic reaction with hyperventilation, tachycardia and the feeling of loss of control, which was successfully treated with benzodiazepines. He described an intensely irrational and unavoidable fear of putting himself in the hands of others -surgeons and anaesthetists in this case. Moreover, the fear of losing control of his body through loss of consciousness or compromise of physical integrity during an operation or surgical intervention was reported. The patient was not able to give his agreement for the operative intervention because of overwhelming panic and anxiety. Due to his intense fear he eventually refused the bypass operation. This dramatic situation led to a condition of anxiety, strain and severe agitation, which led to a psychiatric referral and, consecutively, to an in-patient psychiatric admission.
The patient was relieved by the psychiatric admission and the understanding of his phobic fear. He reported a 20-year history of severe coxarthrosis, which caused serious pain and progressive leg deformation and malfunction, and which had never been operated on because of his fear of surgery. The clinical examination revealed that his left leg was 4.5 cm shorter than his right leg. He also had a marked impaired gait due to a limp in his left leg. Additionally, the coxarthrosis led to an extensive inguinal hernia due to pain induced mismovement. He also refused the necessary inguinal operation for over five years due to the same phobic symptoms. Further phobic symptoms and other symptoms of anxiety were explored, such as his fear about GP visits and discussions with superior colleagues. The patient reported an age of onset in the early adult years. With regard to childhood and adolescence, he described fear symptoms while knocking on or opening 'foreign' doors. Though the patient showed avoidant personality traits, no personality disorder could be diagnosed.
The psychopathological findings at the time of psychiatric exploration were limited to intense fear in relation to the forthcoming surgical procedures and interventions. During the psychiatric exploration, the patient was polite, friendly, and honest. Compulsive symptoms were limited to the repeated checking of electric appliances. As a consequence of his lifelong avoidance strategies he seemed not to feel oppressive limitations in everyday life. Until then, he had never consulted a psychiatrist or a psychotherapist regarding his phobic symptoms. He described being ashamed of his unreasonable fear symptoms. Panic disorder symptoms were not observed at any time during the psychiatric exploration. No history of syncope was found. Family history revealed a suspected anxiety disorder in the patient's father, although he reportedly never consulted any physician or other healthcare professional. Further examinations of the patient such as laboratory tests, duplex sonography, an electroencephalogram and a cranial magnetic resonance imaging were entirely normal. A Specific Phobia was diagnosed according to DSM-IV criteria.
To improve the intense fear reported by the patient when being confronted with the problem of the necessity of the operation, a psychotropic treatment with escitalopram 10 mg once a day and pregabalin 150 mg twice a day was initiated. The patient described an improvement of these fear symptoms. Supported by intensive conversational therapy based on cognitive behavioural techniques, he stabilized and was subsequently discharged. The patient still refused the invasive procedure, as his fear of the procedure continued to overwhelm his fear of dying from a heart attack. Behavioural psychotherapy as an out-patient treatment was recommended in order to diminish the patient's phobic fears.


We describe the case of a 60-year-old Caucasian woman with a positive familial history for dyslipidemia and nephropathy.
The patient was first hospitalized in February 2001 with: hypertension (160/100 mmHg), high lipidic values (cholesterol 372 mg/dl, LDL cholesterol 267 mg/dl, triglycerides 239 mg/dl), creatininemia within the standard limits (0.9 mg/dl), a corresponding GFR of 63 ml/min calculated according to Cockroft and Gault, albuminemia of 3.15 gr/dl, total proteins of 5.7 g/dl, and a micro-hematuria, proteinuria (200 mg/dl) and proteinuria and/or albuminuria ratio of 2 g/g. The main immunological studies, ASO, rheumatoid factor, C3-C4, VDRL, serum immuno-fixation and serum immunoglobulin were normal. The serum markers for HBV, HCV and HIV were negative. The leucocyte formula was normal.
A physical examination ruled out the presence of xanthelasma and corneal arc in the absence of edemas. An ultrasound revealed kidneys which were regular in dimension and structure.
A renal biopsy showed the presence of lipid deposits in the glomerular lumens under the optical microscope after staining with Red-O oil. The interstitium showed a diffuse fibrous edema and tubular atrophy in the areas of fibrosis with a moderate infiltration of inflammatory cells. An arteriole showed hyaline deposits. An immunofluorescence revealed the presence of deposits of IgM and C3 in the sub endothelial seat. An electronic ultrastructural analysis confirmed the presence of thrombi in the lumen of the glomerular capillary loops. The histopathological diagnosis suspected LPG, but ApoE typing identified the polymorphism (E2/2) with a diagnosis of familial type III dyslipoproteinemia.
The patient started treatment with atorvastatin 40 mg/day. We did not use fibrates in association with statin to avoid possible side effects. After one year of therapy we observed a good control of lipid values (cholesterol 250 mg/dl, LDL cholesterol 114 mg/dl) and a reduction of the proteinuria (120 mg/dl). Hypertension was controlled (145/90 mmHg) by means of ACE-inhibitors (irbesartan 300 mg/day, ramipril 5 mg/day), beta-blockers (carvedilole 25 mg/day) and Ca antagonists (nifedipine 60 mg/day).
Four years later in April 2005, the patient was again hospitalized for clinically overt nephrotic syndrome with proteinuria (5 g/24 h) and renal failure (creatinine 2.2 mg/dl). Arterial hypertension (180/100 mmHg) was hardly responsive to treatment. The patient had a low response (cholesterolemia 445 mg/dl, LDL 318 mg/dl, triglycerides 292 mg/dl) to lipid-lowering drugs (atorvastatin 40 mg/day + cholestyramine 4 g/day + Omega3 fatty acids 2 g/day) with the presence of periocular thelasmas.
A renal biopsy revealed the presence of lipids with a fibrous growth of the interstitium and a percentage increase of sclerotic glomeruli with a diagnosis of LPG evolved into nephrotic syndrome (histology will be published in a manuscript in preparation and when published the reference will be provided).
In view of the patient's poor response to pharmacological treatment alone, in July 2005 we decided to associate for the first time in a patient with LPG an LDL-Apheresis protocol (three aphereses in the first two weeks, then one weekly session for two months followed by one apheresis every 15 days) with dextran sulfate columns on the basis of the evidence present in literature for the treatment of the steroid-resistant nephrotic syndrome. [-]
During the first LDL-apheresis (July 2005) with dextran sulphate columns (Liposorber System - Kaneka™), an anaphylactoid reaction occurred. This complication, as described by Olbricht in 1992 in patients undergoing treatment with ACE inhibitors and an LDL-apheresis regimen with dextran sulphate columns, is due to the inhibition of kininases that metabolize bradikynin [].
To avoid stopping the anti-hypertension treatment with ACE-inhibitors we decided to use another LDL-apheresis procedure: the extracorporeal precipitation of LDL-cholesterol induced by heparin in acid pH (HELP System, B. Braun Avitum™ Melsungen Germany). This procedure does not involve complications linked to the use of ACE-inhibitors, following the same protocol previously described.
The effects of a single HELP-apheresis on vascular homeostasis is a simultaneous, drastic reduction within two hours of cholesterol (-52%), LDL-cholesterol (-56%), VLDL-cholesterol (-52%), oxLDL (-47%), Lp(a) (-55%), triglycerides (-50%), fibrinogen (-56%), thrombin (-55%), von Willebrand factor (-56%), factor V (-57%), factor VII (-35%), PCR (-56%), plasma viscosity (-14%), erythrocyte aggregability (-60%), and thrombocyte aggregability (-60%). Also reported in the long-term treatment was an increase of HDL-cholesterol (+14%), peripheral muscle oxygenation (+33-50%), coronary flow reserve (+14%), and cerebral CO2 reactivity (+14%) [].
In the LDL/fibrinogen apheresis procedure (HELP-apheresis), the plasma is obtained by filtration of the whole blood through a 0.55 μm pore-size filter and then mixed continuously in a 1:1 ratio with a solution of a 0.2 M sodium acetate buffer (pH 4.85) containing 100 IU/ml (300,000 UI) of heparin. The pH of the plasma-buffer solution reaches 5.12 and, at this value, the heparin binds the LDL-cholesterol, Lp(a), fibrinogen and triglycerides forming aggregates. These aggregates precipitate and are retained by the precipitate filter. Precipitate filter is a 0.4 μm pore-size polycarbonate filter from which plasma free from LDL-cholesterol, Lp(a) and fibrinogen is obtained and then passed through an anion exchange filter (heparin absorber) to adsorb excess heparin. The last stage of the system (dialysis filter) restores the physiological pH of the plasma and the balance of the liquids, removing excess fluid by ultrafiltration. The liquid used for dialysis is a sterile solution with a bicarbonate concentration of 35 mmol/l. After the dialysis process, the plasma, purified of lipids and fibrinogen, is returned to the patient mixed with the haematic cell components.
We processed 3000 ml of plasma. That means about 1.4 patient plasma volumes in two hours, with HELP machine (Plasmat Futura®, B. Braun Avitum, Melsungen Germany) and a disposable kit. There were no side effects with the HELP. method, except that the patient had problematic vascular accesses leading to flow problems, So, it became necessary to modify some software parameters (most notably the "PA minimum" threshold; software version 2.06.01) to be able to use a 17G fistula needle for the blood withdrawal and a 20G cannula needle for the blood reinfusion during the procedure. With this configuration, the flows were relatively moderate for an LDL-apheresis (blood flow of 50 ml/min and plasma flow of 20 ml/min), to complete the treatment target of 3000 ml. After some procedures we proceeded with the use of an 18G fistula needle in re-entry, maintaining a 17G fistula needle for drawing, obtaining flows that were definitely higher (blood flow of 80-100 ml/min and plasma flows of 25-30 ml/min). By increasing the flows, there was a marked reduction in the duration of the individual procedure, super-imposable to that of a patient with good vascular accesses.
After two months of treatment with LDL-apheresis (10 procedures), the laboratory data showed a progressive increase of albuminemia (from 3.39 to 3.70 g/dl) with partial remission of proteinuria (from 3.3 to 2 expressed as urine protein to creatinine ratio. A ratio of 0.1 is normal - protein and creatinine are expressed in mg/dl); and a progressive decline in creatininemia (from 1.9 to 1.6 mg/dl). The patient's anemia was improving and her arterial pressure was well under control with a reduction of the pharmacological dose, compared to two months earlier. There was also a significant drop in the mean values of TG (from 285 to 231 mg/dl) and LDL-Cholesterol (from 178 to 158 mg/dl) with reduction of xanthelasma. Pre-apheresis fibrinogen and Lp(a) mean values did not show a significant reduction. Considering the patient's clinical condition improvement, we decided to reduce the statins dosage (from 40 to 20 mg/die) continuing LDL-apheresis protocol of one session every two weeks.
Four months after aphaeretic treatment (15 procedures), the patient's albuminemia values were maintained (3.70 g/dl), her creatinine (1.3 mg/dl) and proteinuria (ratio 1.3) were reduced and her arterial pressure was stabilized (120-80 mmHg). There was a further reduction of LDL-cholesterol (105 mg/dl) and TG (134 mg/dl) mean values, with a suspension of cholestyramine and Omega-3 fatty acids treatment and a further reduction of the xanthelasmas. The LDL-Apheresis session was reduced to one session every three weeks.
After ten months (25 procedures) the laboratory data were as follows: creatinine 1.6 mg/dl, albuminemia 4.30 g/dl, proteinuria (ratio 0.13), LDL-cholesterol 106 mg/dl and TG 154 mg/dl. The values of Lp(a) and fibrinogen are unchanged (Figure , ).
After two years of follow up, with a maintenance treatment of one LDL-apheresis session every three weeks in the last period, the mean biochemical values were: cholesterol 199 mg/dl, LDL-cholesterol 110 mg/dl, HDL-cholesterol 76 mg/dl, TG 112 mg/dl, fibrinogen 381 mg/dl, creatininemia 1.5 mg/dl, Proteinuria ratio 0.9, arterial pressure 120-80 mmHg. The pharmacological therapy is unchanged.
The sequence of the ApoE gene made in 2007 showed that the patient was homozygous for epsilon-2 allele (polymorphism E2/2 with Cys112 and Cys158 in the mature protein) and heterozygous for a novel mutation in exon 4: c.502 C>T [Arg 150>Cys of mature protein]. The mutant Apo E (ApoEMODENA) expresses a new residue of Cys in place of an Arg. This new cysteine residue could form a disulphide bridge with the other Cys residue of the E2 isoform resulting in ApoE polymerization (dominant negative effect). This phenomenon is probably the cause of both dyslipidemia and lipid thrombi in the glomerular capillaries [].


An 83 year old retired Caucasian lady was admitted to a UK hospital with a recent history of back pain without any trauma. She had no significant past medical history of note and her only regular medication included a statin for cholesterol. She was a non-smoker and drunk only minimal amounts of alcohol. X-rays on admission demonstrated severe osteoporosis with multiple collapsed lumbar vertebrae. Whilst awaiting a brace and social support she developed diarrhoea and vomiting. An initial stool sample was negative for clostridium difficile serotoxin. Over the next few days her clinical condition deteriorated and by day 6 her C-reactive protein was 357. She developed abdominal distension, pain and a plain x-ray showed centralised dilated small bowel loops. A subsequent CT scan of her abdomen revealed small bowel obstruction together with mural thickening of the distal ileum (see Figure ).
Following CT the patient developed signs of localised peritonitis and underwent a laparotomy. At surgery necrosis and ischaemia was seen in a large portion of mid-ileum together with large quantities of pus and a localised perforation. A small bowel resection of 60 cm was performed. Histology revealed an acute gangrenous ileitis. Blood, urine and stool cultures were all negative but reverse transcription polymerase chain reaction (RT-PCR) of stool cultures revealed Norovirus genogroup II. Immunoassay of the stool was negative for rotavirus and adenovirus. No specific testing for astrovirus was performed. Immunological testing of the histological specimens was not performed.
The patient had no prior history of vascular disease to suggest the cause of the ileitis was ischaemic enterocolitis. Furthermore despite the patient's back pain she had been mobilising around her bed in the hospital therefore it is unlikely that the cause of the ileitis was paralytic ileus secondary to immobility. The patient received only as required opiate analgesia and this was co-administered with appropriate laxative cover to avoid constipation. A diagnosis of acute gangrenous ileitis secondary to Norovirus was therefore made. It was postulated that the virus had triggered a localised inflammatory response leading to necrosis which had continued despite clearing of the virus by host immune responses. The virus was thought to be a nosocomial infection as there was no recent history of foreign travel or contact with individuals demonstrating the symptoms of gastro-enteric disease prior to admission. However antibody testing for IgG and IgM was not performed therefore the length of infection with the virus was unclear.
Following surgery the patient developed a pelvic collection requiring CT guided drainage which matured into an enterocutaneous fistula. The fistula was treated conservatively and sealed spontaneously at 10 weeks at which point she was discharged.


An 80 year-old man underwent aortic valve replacement with a Carbomedics Sulzer size 21 mm mechanical prosthesis in 1999 for severe aortic stenosis. The patient made a successful recovery and had significant improvement in his initial symptoms without readmission for valve dysfunction.
In 2008, the patient represented with episodes of pulmonary oedema, worsening dyspnoea, and haemolytic anaemia requiring regular transfusion. Transoesophageal echocardiography (TOE) demonstrated moderate to severe aortic regurgitation with at least two eccentric jets, suggestive of PVL (Figure ). Overall systolic function was preserved. Coronary angiogram revealed no significant disease. In view of the combination of significant PVL, dyspnoea and haemolytic anaemia, in a surgically fit patient, a decision was made to proceed surgically.
Despite thorough inspection at the time of operation, no PVL was found. However, a suture on the valve ring with almost 10 knots was found in an unusual position, vertical to the outflow of the valve within the area of the non-coronary sinus. This suture was obstructing one of the valve leaflets preventing complete closure (Figure ). The stitch was removed and a pledgeted suture applied from the external part of the aorta to the aortic valve ring to prevent incomplete opposition between the annulus and sewing-ring. Intraoperative TOE confirmed normal valve function. The patient made a successful recovery and was discharged home within one week. A transthoracic echo (TTE) on the sixth postoperative day confirmed normal valve function.


This 53-year-old Indo-Aryan man of Indian nationality presented to us with the symptoms of dull aching pain in the right upper quadrant of the abdomen for seven months. There is no history of fever, vomiting, gastrointestinal bleeding. There is no significant past medical or family history. He was detected to have both diabetes mellitus and hypertension during evaluation. Which were easily brought under control with oral hypoglycaemic agent (glimepiride 2 mg once daily) and anthypertensive (ramipril 5 mg once daily). Physical examination was unremarkable. Ultrasonography revealed a hyperechoic SOL (9.9 × 7.7 cm) in the right supra-renal region. CT scan showed a well defined rounded patchily hypodense lesion (8.43 cm × 7.69 cm) with discrete capsule containing fat density areas seen at right adrenal area, adjacent fat plane was maintained. The Hounsfield unit of the fat containing areas was -105 (Figure and Figure ). Right kidney has been pushed downwards by the tumour. His complete blood counts, liver function tests and chest X-ray were normal. Urinary metanephrine and serum potassium levels were normal. He was taken up for laparoscopic adrenalectomy as the tumour was symptomatic as well as large in size. Surgery was done in left lateral position. First port (10 mm) was made by open technique in right anterior axillary line just below the costal margin. After creating the pneumoperitoneum three more ports were made, one 5 mm, 5 cm behind the first port, one 10 mm, 5 cm in front of the first port and one 5 mm close to the midline below the costal margin for retracting the liver. After exploration subhepatic peritoneum is divided and right lobe of liver retracted upwards with a liver retractor introduced through the extreme left port. There were few adhesions between the left surface of the tumour and the inferior vena cava (IVC), these were divided with hook diathermy. Left border of IVC was cleared caudally upto right renal vein. Right adrenal vein was dissected out, clipped and cut. Inferior adrenal artery was found to be arising from the right renal artery, which was also clipped and cut. But no significant sized superior and middle adrenal artery was found. After the whole gland was mobilized it was taken out through a right flank incision of 6 cm. The specimen size was 11 cm × 10.5 cm and weighed 405 grams (Figure ). One 24 Fr tube drain was placed in the right subhepatic space. Postoperative recovery was uneventful. Drain was removed after 24 hours. Patient was discharged from the hospital on day 6. Microscopic examination showed predominantly mature adipose tissue interspersed with extramedullary hematopoietic components of myeloid, erythroid and megakaryocyte series suggestive of adrenal myelolipoma (Figure and Figure ). Post surgery the patient is doing well after 12 months.


A 46-year-old Pakistani man presented to our hospital with a 2 months history of progressively increasing cough and left lower chest pain. Initial evaluation was done using a chest x-ray and he was found to have a large mass involving the lower portion of the left chest. Computed tomography (CT) scan was obtained next to better delineate the disease process (Figure ). It showed a 16 × 15 cm mass involving the left chest wall and left lower lobe of the lung with invasion into the pericardium and left hemidiaphragm. There was no pericardial or pleural effusion. CT scan of the abdomen-pelvis was normal.
Trucut biopsy of this mass showed features of SCS. In the absence of effective chemotherapy and obvious metastasis, the patient was planned for a complete resection of this tumor. The tumor was exposed via a left posterolateral thoracotomy approach. Intra-operatively, a large tumor with extensive involvement of the left lower chest wall from the 4th to 10th ribs was seen. It was also involving the left lower lung lobe, left hemidiaphragm and pericardium (Figure ). The mass was removed en bloc with all involved ribs, left lower lung lobe, left hemidiaphragm and pericardium. Final pathology confirmed it to be SCS sarcoma with negative histological margins. The post operative course of the patient was unremarkable. He was discharged on the 9th postoperative day. At follow-up after one year, the patient has shown no recurrence of the disease.


A 37-years-old primigravida at 40 weeks gestation was brought to our hospital by ambulance following collapse at home. No obstetric notes were brought in. On admission she was anxious, apyrexial, dyspnoeic, and distressed.
On clinical examination she was hypoxic, with oxygen saturation of 68% on air and respiratory rate of 30/minutes. Blood pressure was 150/90, and Glascow coma scale was 11/15. There were no signs of labour. Soon after arrival she had a seizure. Following the seizure there was an episode of fetal bradycardia and an urgent caesarean section was performed under GA. The baby was delivered in good condition. There was no evidence of placental abruption or any other cause for fetal bardycardia. Patient's vitals were stable during the caesarean section. She was transferred to Intensive Care Unit, where she was intubated and ventilated. A CT chest showed extensive bilateral pnenumothoarces of greater than 70% in the left side and extensive opacities in the semicollapsed right lower lobe (see Figures and ). The CT head was normal. A left-sided chest drain was inserted on the same day. This was removed on the following day after patient's clinical condition had improved. Patient has no symptoms or signs which suggestive of Pre-eclamsia.
Following the caesarean section the family arrived. At this stage we found that the patient had longstanding right pleural endometriosis with multiple pneumothoraces and hydrothoraces and underwent right-sided pleurodesis in 2003. This lady was booked in at tertiary hospital for pregnancy care. She had regular followups with a Chest physician and Obstetrician. At 29 weeks gestation the patient had presented with mild dyspneoa and the chest X-ray revealed a small effusion but no significant pneumothorax. The cardiothoracic surgeon suggested that since the pleura was well stuck down, there was a low risk for expanding pnuemothorax. This patient still presented with severe hypoxia with pneumothorax. The Cardiothoracic surgeon further advised assistance with instrumental delivery as small risk of increased pneumothorax in the second stage of labour during pushing. Epidural or spinal anaesthesia was recommended and to avoid General anaesthesia. If general anaesthesia was needed then intermittent positive pressure ventilation should be used. The Obstetrician had planned for induction of labour at 41 weeks gestation. On the 4th day of postcaesarian section, the patient again complained of shortness of breath. On general examination the patient was dyspneic and tachypneic. Her blood pressure was normal, she had no proteinuria, and her liver function and platelets were within normal limits.
Chest X-ray showed that she had left-sided lower lobe pneumonia and was started on intravenous tazocin, IV gentamicin, and then on oral erythromycin. Patient recovered well and was transferred to a tertiary hospital.


A 38-year-old Egyptian woman was admitted to Cairo University Hospital with extensive exfoliation of her skin. Two weeks prior to her admission, she delivered a healthy baby by uncomplicated caesarian section.
Few days after her delivery, she developed pruritic erythematous patches with multiple pustules on its margins on her thighs, groins and abdominal wall. She was treated empirically with hydrocortisone 1% cream. Few days later, the rash progressed and involved most of her body, she felt weak and developed chills. On examination, she appeared ill with a blood pressure of 90/60, pulse rate of 120/min, temperature of 38°C and respiratory rate of 20/min.
She had erythroderma, multiple crusted plaques and extensive skin exfoliation of her trunk and extremities sparing her eyes and mucous membranes (Figure ). There were no nails abnormalities noted. Chvostek and Trousseau signs were negative. There were no personal or family history of similar condition.
Thyroidectomy was performed for toxic nodular goiter during the second trimester. She developed secondary hypoparathyroidism after surgery. She was not compliant with her medications which included calcium, L-thyroxine and vitamin D.
Laboratory studies revealed leucocytic count of 21.500/ml (normal 4300-10800/ml) with 84% neutrophils (normal 45%-74%), total calcium 5.2 mg/dl (normal 8.5-10.5 mg/dl), phosphorus 5 mg/dl (normal 2.5-4.5 mg/dl), albumin 3.2 gm/dl (normal 3.5-5.5 gm/dl), blood urea nitrogen 64 mg/dl (normal 10-20 mg/dl), creatinine 1.4 mg/dl (normal < 1.5 mg/dl). Thyroid stimulating hormone 38.3 μU/ml (normal 0.4-0.6 μU/ml), thyroxine 0.39 Pmol/ml (normal 9-24 Pmol/ml) and parathormone 6.1 Pg/ml (normal 11-54 Pg/ml).
Intravenous fluids, oral prednisone 60 mg/d, calcium gluconate 2 g/d, Calcitrol 0.25 μg/d, intravenous clindamycin 1200 mg/d and intravenous vancomycin 1 g/day were given. The correction of hypocalcaemia (within five days) was accompanied with rapid improvement of her skin disease and general condition, indicating the importance of correction of hypocalcaemia in patients with impetigo herpetiformis precipitated by hypoparathyroidism []. The skin biopsy was consistent with pustular psoriasis. (Figure )
The patient was discharged from the hospital three weeks after her admission with near complete recovery of her skin (Figure ).
Hebra introduced the term impetigo herpetiformis (IH) to described five pregnant women, all of them were in toxic condition, febrile and had extensive pustular eruption. Hebra classified it as a specific dermatosis of pregnancy []. IH usually present during the third trimester with a progressive course during pregnancy and then rapid resolution occurs during the puerperium. Few cases similar to our case were initially reported during the puerperium [-].
It is controversial, whether IH is a form of generalized pustular psoriasis based on the identical histopathology, or a distinct entity. The absence of personal and family history of psoriasis, the association with pregnancy and hypocalcaemia, its recurrence with subsequent pregnancies and the absence of development of chronic plaque psoriasis might suggest that IH is a distinct entity [,,].
IH presents mainly by pustular eruption that begins symmetrically in the flexural and intertriginous areas and then extends centrifugally. The lesions are erythematous patches with sterile pustules at their margins. They form plaques and pustules that become eroded, then crusted. Generalized eruption and even exfoliation of the whole body can also occur as in our case. Mucous membranes can be also affected [].
IH is usually associated with systemic features as fever, sweating, tachycardia, nausea, diarrhea, vomiting, lymphadenopathy, splenomegaly and tetany, in severe cases renal or cardiac failure may occur. Moreover, IH is associated with increased incidence of congenital anomalies and placental insufficiency resulting in increased risk of intrauterine growth retardation, stillbirth and neonatal deaths [].
Although hypocalcemia in many cases of IH may be a secondary phenomenon due to extensive skin inflammation that result in extravasation of albumin and calcium bounded to it to the interstitial space []. It had been established that IH could be precipitated by hypoparathyroidism and hypocalcaemia, and could be cured by correction of hypocalcaemia in patients with hypoparathyroidism. Moreover there are several reports of IH occurring in men and non pregnant women with hypoparathyroidism and hypocalcaemia, suggesting the triggering role of hypocalcaemia in the disease process [,]. Katsambas et al suggested that the decrease of serum calcium (main decrease is in nonionized fraction with mild decrease in ionized calcium) and vitamin D during pregnancy and puerperium play a role in the development of IH during pregnancy and puerperium [].
There are no guidelines for IH treatment. Fluid and electrolytes especially calcium should be monitored and normalized []. Corticosteroids are commonly used [,]. There are reports of successful treatment of IH during pregnancy with cyclosporine []. Other studies reported that Retinoids, methotrexate, psoralen and ultraviolet A (PUVA) can be used successfully during puerperium [,].


A sixty-four-year-old lady presented to her general practitioner
(GP) with acute onset of unsteadiness and dizziness associated with movement. She
visited her doctor with a complaint of feeling dizzy and faint but had a blood
pressure of 113/70 mmHg. She had no abnormalities on general, vestibular,
neurological, and otological examinations,
including no nystagmus. The dizziness was described as repeated attacks of a sensation
of internal moving; that is the patient was “whirling”, but the room was still.
The attacks lasted for a few hours at a time. Her symptoms worsened over the
following week, disturbing her daily activity and leading to nausea, vomiting,
and prostration. The GP had noted that she had irregular and erratic eye
movement and had developed a postural drop in her blood pressure, from
113/70 mmHg to 97/63 mmHg on standing.
A week later she was permanently dizzy and nauseous and had noticed
some difficulty in pronunciation of words. The dizziness was now described as a
constant sensation that she was turning and tilting over, when she knew she was
upright, and the room was still. This was noted during both still and on movement. There had also
been the occasional sensation that the room was spinning around, although these
were the only fleeting. She had no visual disturbance, hearing problems, weakness
or numbness, and her neurological examination was normal. There was no
nystagmus, and fundoscopy was normal. Blood tests were also normal. She was treated with antiemetics including
prochlorperazine; with a presumed diagnosis of vestibular failure, and her GP referred
her to the otolaryngology services for further treatment and to investigate for
an organic cause.
On admission, she was clearly unwell and complained of a mild
bilateral tinnitus. She had no headache, neck stiffness, or limb weakness. On
examination, she was noted to have a subtle head nodding tremor or titubation.
This was associated with a low-frequency tremor of the upper limbs, which appeared
to increase on intention. She had erratic eye movements and it was very difficult to elicit any
nystagmus, even with Frenzel glasses, whether spontaneous or positional. This
was due to the difficulty in keeping her eyes open secondary to overwhelming
nausea. Her symptoms of nausea improved on closing her eyes. The patient found that
it very difficult to keep her eyes still and to focus on a stationary object
and she was unable to smoothly pursue a moving target. There was clearly a
fixation instability and it appeared to be in the form of conjugate involuntary
saccadic oscillations. It was concluded that this was characteristic of opsoclonus.
There was, however, a fleeting vertical nystagmus on upgaze, which may have
indicated a gaze-evoked cause, but with no obvious horizontal element. Examination
of the ears with otoscopy was normal. A Halmagyi-Curthoys head thrust test was
attempted, but proved difficult to interpret due to the stimulation of
vomiting. It was noted, however, that the patient was unable to fix on a
stationary object during head rotation indicating a probable suppression of the
vestibulo-ocular reflex (VOR). Due to
the significant nausea and vomiting, a caloric canal test was not performed.
She had subtle
cerebellar signs on subsequent examination, including dysmetria and
dysdiadocokinesis. Romberg's test was negative. Dix-Halpike test was symptomatically
positive, with vomiting but with no rotatory nystagmus and no positional
dependence. Her gait was not tested, as she was too unsteady. She was given
intravenous fluids and steroids and treated symptomatically for the nausea and
vomiting.
It was
postulated that there was a central cause for her symptoms, due to the
combination of cerebellar signs, fixation instability/opsoclonus, possible
upbeat nystagmus, and VOR suppression. Therefore, a magnetic resonance scan (MRI)
of the brain was ordered. This revealed a large space-occupying lesion in the
right lobe of the cerebellum, with a smaller lesion in the left lobe ().
The patient was referred directly to the neurosurgeons who performed a
suboccipital craniectomy and excision of the cerebellar tumour. The histology
of the lesion was metastatic adenocarcinoma.


A 35-year-old gentleman, presented with insidious-onset weakness of the right wrist of 2 months' duration; the weakness of the right wrist had been followed, 15 days later, by similar weakness of the left wrist. There were no sensory symptoms. He had been employed in a battery shop for the last 8 years. On examination, there was pallor and a dark line on the gums. Neurological examination revealed wasting and weakness of the wrist extensors bilaterally (MRC grade: 3/5) []. There was minimal reduction in pain sensation along the ulnar border of the right forearm. The blood lead level was 55.8 μg/dl (acceptable limit: 9 μg/dl). The peripheral smear did not reveal basophilic stippling. A diagnosis of lead neuropathy was considered and Penicillamine 250 mg twice a day was initiated. After 25 days, there was an improvement of 25% in power, and at the follow-up visit after 4 months his power had improved by 50%.
The peripheral nerve conduction parameters are mentioned in []. The conduction velocities were normal in all patients. In addition, patient 1 had reduced CMAP amplitude of the right common peroneal and patients 3 and 5 had reduced CMAP amplitude of the right median nerve. Most of the sensory conduction parameters were normal in all the patients, except for slightly decreased SNAP of the right radial nerve in patient 3 and mildly decreased SNAP of the right median and ulnar nerves in patient 4, suggesting mild sensory involvement.
Three of the patients[] were treated with oral d-penicillamine (500–750 mg/day), while patients 2 and 4 received meso 2,3 dimercaptosuccinic acid (DMSA). Follow-up data was available only for patient 3.


A 47-year-old woman presented with 2 days' history of right facial weakness and pain in the right periauricular area. Two months earlier she had had acute-onset deafness on the right side. The general physical examination was unremarkable. Neurological examination showed right lower motor neuron facial palsy and reduced taste sensation on the right half of the tongue. Hearing was reduced on the right side and the Rinne test and Weber test were suggestive of sensory neural hearing loss (SNHL).
Although the erythrocyte sedimentation rate (ESR) was 105 mm/h, other routine laboratory investigations were normal. Magnetic resonance imaging (MRI) of the brain showed mild diffuse thickening and gadolinium enhancement of the duramater in the falx cerebri and cerebellar tentorium. Furthermore, an intensely enhancing, enlarged pituitary gland was also noted [Figures and ]. An audiogram revealed moderate right SNHL.
Review of the patient's medical history showed that she had had complaints of a dry sensation of the mouth, burning eyes, and polyarthralgias for the past 2 years. Rheumatoid factor was positive at a titer of 53 IU/ml (normal: <15) and antinuclear antibody (ANA) was positive at a titer of 1.10 by the enzyme immunoassay technique (normal: <0.7). Antibodies to SS-A and SS-B were also strongly positive. Anti-ds DNA and antibodies to Sm, RNP, and Scl-70 were negative. Serum immune electrophoresis revealed no monoclonal gammopathy. Schirmer test showed decreased lacrimation and a lower labial biopsy showed significant lymphocytic infiltration []; these findings were consistent with the diagnosis of Sjögren syndrome (SS). Nerve conduction study revealed bilateral mild carpal tunnel syndrome and right facial neuropathy. Additionally, a cerebrospinal fluid (CSF) study showed normal protein and sugar and a cell count of 5 cells/mm3 (all lymphocytes). Gram's staining and AFB staining of the CSF was normal and the VDRL test was negative. Serum angiotensin converting enzyme (ACE) level was also normal. In view of the pituitary gland infiltration, an endocrine workup was done. Thyroid function test, serum cortisol and ACTH levels, and the water deprivation test for diabetes insipidus were all normal; serum prolactin was mildly raised at 37.6 ng/ml (normal: 2-25 ng/ml). Based on these findings, we diagnosed primary SS, with probable lymphocytic CNS involvement. The patient was treated with IV methylprednisolone pulse therapy, with 1 g/day for three successive days, followed by 0.5 mg/kg/day oral prednisolone, with gradual tapering of the dose. Later, weekly methotrexate at a dose of 10 mg/week was added. Follow-up brain MRI after 6 months of treatment showed a minimal decrease in the pituitary gland enlargement and the meningeal thickening []. The patient's symptoms, except for the dryness of the mouth, resolved with treatment. Over the next 1 year, she had three episodes of transient diplopia due to lateral rectus palsy. She recovered from all these attacks within a few weeks after the dose of steroids was increased. Two years after the first evaluation, she was readmitted with acute-onset dysphagia, nasal regurgitation, and hoarseness of voice. On examination, she was found to have right IXth, Xth, and XIIth cranial nerve palsies, without any long tract signs or cerebellar signs. Repeat MRI did not reveal any fresh brainstem lesions. She was treated with a 3-day course of methylprednisolone injection (1 g/day) and recovered completely in 2 weeks' time.


A 51 year-old heavily built male patient presented to the hospital with a history of gradually progressing anasarca of two months’ duration. Initially, the patient had had pedal edema which progressed later on to involve the whole body. There were no significant cardiorespiratory complaints. On screening, the patient was found to have significant proteinuria and was referred to us.
The patient had a significant medical history: he was a known hypertensive for seven years on regular treatment, had dyslipidemia, was diagnosed as having obstructive sleep apnea, and had a history of significant NSAID intake five years ago for around one year for vascular headaches. His medications included ramipril, losartan potassium, and atorvastatin. Obstructive sleep apnea was being managed conservatively. There was a positive family history of hypertension. Of significance is the fact that he denied any recent history of NSAID intake.
Physical examination found a 97 kg, afebrile man with a BMI of 32.01 kg/m2 and a blood pressure of 140/90 mm Hg. He had mild pedal edema but the results of the other aspects of the general physical and systemic examination was normal. Laboratory results included a hemoglobin level of 15.4 g/dL (154 g/L), white blood cell count of 10,800 × 103/µL (×109/L), ESR of 55 mm, blood urea of 50 mg/dL, serum creatinine of 2.4 mg/dL, estimated CCR of 50 ml/min, total cholesterol of 198 mg/dL, serum triglyceride level of 151 mg/dL, serum HDL cholesterol level of 42 mg/dL (on statin therapy), total serum protein level of 6.2 g/dL, and a serum albumin level of 2.8 g/dL. Urine was suggestive of 4+ proteinuria and the 24-h urinary protein level was 4.9 g/24 h and was positive for active sediments. The results of thyroid function tests were within the normal range and echocardiography was suggestive of concentric left ventricular hypertrophy with type 1 diastolic dysfunction. Ultrasonography of the abdomen was suggestive of hepatomegaly with grade 2 fatty liver and a right kidney with a size of 12.5 cm × 6.3 cm and a left kidney of size 13 cm × 6.4 cm. Both the kidneys had normal echogenicity and had maintained their corticomedullary differentiation. Some of the special investigations have been shown in .
Kidney biopsy showed ten glomeruli, five of which showed partial to complete fibrocellular crescents []. The capillary basement membrane was thickened and wrinkled and there was a focal increase in the mesangial matrix and cellularity; no spikes could be seen. There was marked tubular atrophy, interstitial edema, and fibrosis as well as a diffuse mononuclear cell infiltrate in the interstitium. The vessels and the basement membrane were unremarkable. On immunofluorescence, glomeruli showed linear positivity for IgG (++), IgM (+), fibrinogen (+), and focal IgM and IgA deposition []. The diagnosis was crescentic glomerulonephritis with significant immune deposits.
The patient was started on intravenous, pulsed methyl prednisolone therapy along with oral prednisolone (1 mg/kg). The renal functions of the patient improved for a while, only to worsen within 2–3 months. Our patient also developed side effects of corticosteroid therapy. At this point, intravenous, pulsed cyclophosphamide was started. Despite all our efforts, his renal functions continued to deteriorate and he was put on maintenance hemodialysis.


A 9-year-old girl, known GT patient, who presented with gum bleeding, was referred from the Pediatrics Department of M.S.R.M.C to the Department of Periodontics M.S.R.D.C. Her medical history revealed that she was born to consanguineous parents. At six months of age she had an episode of epistaxis following trauma and was given blood transfusion for the same. Since then she has had repeated episodes of epistaxis and episodes of bleeding from lips, gums, and tongue due to minor trauma. She had been hospitalized more than 18 times for repeated transfusions to control bleeding. Other clinical manifestations of GT like spontaneous bleeding, menorrhagia, bleeding of purpuric type were absent. On oral examination, her gingival status showed generalized pink colored gingiva. However, it was red, soft, and edematous with stippling and knife-edge lost in mandibular anterior region. Papillary gingival enlargement and bleeding on probing was seen in madibular anterior region. A diagnosis of mild gingivitis with normal periodontal status was made [].
Routine laboratory investigations revealed normal hemoglobin (9.6%), platelet count (3,77,000/mm3), PT (10.5 seconds), active PTT (29 seconds), and bleeding time (15 seconds). The platelet aggregation test presented no agglutination with epinephrine, ADP, and collagen.
Periodontal treatment (scaling and polishing) under platelet transfusion was given followed by and oral hygiene instructions. The patient was prescribed 0.12% chlorhexidine and tranexamic acid mouth rinses. The therapy was successful with decrease in gum bleeding and the patient returning to status quo. Thereafter, she had weekly follow-up for one month and monthly recalls for the next six months [].


The first case was a 5-year-old Saudi female who had severe, frequent bloody diarrhea for two years associated with intermittent abdominal pain, poor appetite and failure to gain weight. At age of 3 years, she was treated at her local hospital for amoebic dysentery with antibiotics (sulfamethoxazole-trimethoprim and metronidazole) with no obvious improvement, followed by eliminating dietary milk products with some improvement, but she later had a recurrence of symptoms. Sigmoidoscopy in the local hospital showed a normal looking mucosa and biopsies showed chronic non-specific colitis; subsequently, the patient was started on prednisolone empirically with good response, but whenever the steroid dose was tapered, she started to bleed again from the rectum. She was referred to our center as having steroid-dependent colitis for further management. Examination revealed a pale, non-thriving child with both weight and height below the fifth percentile for age. The rest of the systemic examination was normal. Her hemoglobin was 5.3 mg/dL (normal, 11.0-14.0 mg/dL), mean corpuscular volume was 64.1 fL (normal, 80.0-94.0 fL), mean corpuscular hemoglobin was 19.9 pg/cell (normal, 27.0-32.0 pg/cell), the erythrocyte sedimentation rate was 31 mm/h, and stool for occult blood was positive, serum albumin was 38 g/L (normal, 32-46 g/L), and total protein was 69 g/L (normal 65-81 g/L). Colonoscopy revealed tiny angiodysplastic lesions in the rectum, sigmoid colon, and the ascending colon (). The transverse colon and cecum again showed small hemorrhagic angiodysplastic lesions with typical fold processes of dilated superficial mucosal capillaries. No ulcers or erosions were seen (). The upper gastrointestinal endoscopy was normal. The steroid was tapered and stopped. She became blood transfusion-dependent, requiring one transfusion every 3 to 4 weeks. With involvement of the whole colon with angiodysplastic lesions, a normal upper gastrointestinal endoscopy and with moderate-to-severe symptoms requiring multiple blood transfusion, the patient underwent total colectomy and ileoanal anastomosis with a smooth post-operative course. Histological examination was consistent with angiodysplastic lesions in different parts of the colon (). Follow-up in the clinic up to 3 years post-surgery showed that the patient had no more rectal bleeding. Her growth improved and her hemoglobin stabilized at >10 mg/dL.


A 2-year-old male was admitted at 5 months of age with fever and bronchopneumonia. He was treated with antibiotics and improved. Two weeks post-discharge, the infant developed hematemesis and melena. He was hemodynamically stable with a hemoglobin of 6.2 mg/dL (normal, 11.0-14.0 mg/dL) and needed blood transfusion. The liver and renal function tests were unremarkable. Upper gastrointestinal endoscopy in a local hospital revealed angiodysplasia at the greater curvature of the stomach with some oozing points. There were no esophageal varices and no ulcers. He was referred to our center with recurrent hematemesis for further management. At the age of 1 year, upper GI endoscopy at our center revealed a normal esophagus with few angiodysplastic lesions over the body of the stomach while the duodenum was normal. Colonoscopy showed dilated blood vessels consistent with angiodysplastic lesions from the rectum to the mid-ascending colon. He was treated conservatively, without surgical intervention. He had no further bleeding and was placed on iron therapy. At the age of 6 years, he was seen in the clinic and had a weight and height above the tenth percentile. His hemoglobin was 13.3 mg/dL while maintained on an iron supplement.


A 7-day-old male infant, a product of a full-term in vitro fertilization pregnancy was delivered by lower segment cesarean delivery secondary to fetal distress by a mother with primary infertility for six years. The baby was dusky after birth and was resuscitated with oxygen using an Ambu bag, but did not need intubation to resolve transient tachypnea of the newborn. He was fed with artificial feeds (cow's milk formula). On day 3, he had a bloody stool, with no abdominal distension and audible bowel sounds. He did not appear septic and vital signs were normal. He was placed on nil per OS nothing by mouth status and started on intravenous ampicillin and gentamicin after appropriate cultures were taken. An abdominal x-ray was unremarkable. His complete blood count, including platelet count and coagulation profiles were normal. Stools on day 6, 7 and 8 were positive for occult blood. He underwent colonoscopy on day 8, which revealed angiodysplastic lesions oozing blood. The lesions increased in number as the scope advanced proximally to the sigmoid and descending colon and decreased toward the transverse and ascending colon. Bleeding appeared whenever air or water were applied directly over the lesions. The mother refused upper GI endoscopy for evaluation of the rest of the gut. The patient was treated with oral iron supplementation and discharged home. On follow-up, he had no more bleeding and received iron therapy as needed. At 3 years of follow-up, the baby was growing well with no rectal bleeding and had a stable hemoglobin of 11 mg/dL.


The patient was an 82-year-old Japanese woman who was diagnosed with Alzheimer's disease according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) and International Classification of Diseases, 10th edition (ICD-10) criteria. Brain computed tomography (CT), magnetic resonance imaging (MRI), and single photon emission computed tomography (SPECT) were also performed. Brain CT showed brain atrophy and ventricular enlargement, and MRI showed small infarcts in the brain. N-isopropyl- [123I]p-iodoamphetamine ([123I]-IMP)-SPECT showed the reduction of blood flow in the posterior cingulate cortex and lateral occipital cortex. Since she has hypertension and diabetes, antidiabetic and antihypertension treatments were administered before the development of delirium. She was hospitalised due to lung congestion that was detected by chest radiography. Her sleep disturbance was not improved by benzodiazepines, and she developed visual hallucinations of something. A psychiatric consultation was scheduled, and revealed disorientation and memory deficits. Her Delirium Rating Scale (DRS) [] and Mini-Mental Scale Examination (MMSE) [] scores were 17/32 and 20/30, respectively. Treatment with fluvoxamine (25 mg) was initiated after dinner, and next day increased to 50 mg. At 2 days after beginning treatment with fluvoxamine, her DRS score had decreased to 5/32, and both her delirium and sleep disturbance improved.


The patient was a 77-year-old Japanese woman who had been diagnosed with Alzheimer's disease according to the DSM-IV and ICD-10 criteria. Brain CT, MRI, and SPECT were also performed. Before the development of delirium, she had been treated with olanzapine (5 mg) because of her disorientation. She was hospitalised due to her persecutory delusions. At the time of hospitalisation, her DRS and MMSE scores were 17/32 and 21/30, respectively. Treatment with fluvoxamine (50 mg, twice a day) was initiated, and the next day increased to 100 mg since there were no gastrointestinal side effects. Her tendency to reject medication gradually improved 3 days after beginning treatment with fluvoxamine. At 1 week later, her DRS score had decreased to 8/32, and her condition is currently stable.


A twenty-year-old Senegalese black woman, was admitted with a three-months history of spontaneous abdominal mass associated with a pain. There were no histories of trauma or infection. On examination, there were an abdominal mass in the left hypochondrium and epigastric area. This mass was steady, with a diameter of 20 cm. Hydatid serology was negative and blood formula was normal. Ultrasonography found a voluminous mixed fluid mass without specifying its origin. CT scan found a splenic cyst mass with net lining, regular, without calcifications, without enhancement after contrast injection (Figure ). Its content was homogeneous liquid without tissue structure. She referred to a splenic cyst with splenic parenchyma remaining below 25%. A median laparotomy found a splenic pseudotumor cyst with a rich vascular area (Figure ) and the persistence of substantial thickness splenic parenchyma encompassing cyst. A total splenectomy was performed. The postoperative care consisted of a vaccination against meningococcus, pneumococcus, and Haemophilus influenzae and antibiotic-based Oracilline. Her progress has been satisfactory. The pathological examination of surgical specimen found a pseudo cyst from resorption of splenic hematoma without an epithelial lining, with a weight of 4100 g.


A 58-year-old female, Irish, Caucasian patient presented, on a background history of chronic anaemia, with fatigue, palpitations, dyspnoea and haemoglobin of 5.4 g/dL. She had received intermittent blood transfusions during the previous three years. Oesophagogastroduodenoscopy and colonoscopy were normal. She was positive for occult blood. Computed tomography (CT) enteroclysis was performed which demonstrated nodular thickening of the distal jejunum (Figure ). CT mesenteric angiogram demonstrated multiple subcentimeter hyperenhancing foci identified throughout the jejunum with normal enhancement of the aorta and mesenteric vessels (Figure ). The patient underwent antegrade double-balloon enteroscopy (DBE) and multiple hypervascular polypoid lesions were found resembling bunches of grapes and extending over a section of 30-40 cm in the mid-jejunum (Figure ). The distal margin of this segment was tattood.
The patient underwent a mini laparotomy via a 5 cm incision, with segmental jejunal resection and primary hand-sewn anastomosis. She made an uneventful post-operative recovery. Histology demonstrated sections of jejunal polyps showing multiple cavernous haemangiomas, many of which showed organizing thrombus. Given the multiplicity, these were consistent with the blue rubber bleb naevus syndrome.


A 79-year-old Caucasian Italian woman affected by chronic atrial fibrillation and not treated with oral anticoagulants, cardioverted to sinus rhythm during a gastric endoscopy; she then showed a sudden onset loss of consciousness. She was admitted to the emergency department, where pO2 saturation, arterial blood gases analysis, electrocardiogram and laboratory testing were all found to be normal. Neurological examination showed coma, horizontal and vertical gaze palsy, tetraparesis and bilateral miosis. Non-enhanced computed tomographic scanning of her head was unremarkable. The patient was then admitted to the neuro-geriatric ward, where an emergency complete ultrasound examination was performed. An extracranial duplex sonography of the carotid and vertebral arteries was unremarkable. A transcranial Doppler with suboccipital approach showed the typical pattern of 'dampened flow' (mean flow velocity 14.1 cm/sec; resistance index (RI) 0.62; pulsatility index (PI) 1.10) on the basilar artery at 75 mm depth [,] (Figure ). The dampened flow is a typical sign of recanalization in the case of intracranial artery occlusion [,]. A transcranial Doppler with transtemporal approach showed normal findings on middle, anterior and posterior cerebral arteries bilaterally. The flow in the posterior cerebral arteries was normal because there was activation of the posterior communicating arteries.
Low-molecular-weight heparin at therapeutic dosage (enoxaparin 1 mg/kg subcutaneously twice daily) was started immediately. Two hours later, the symptoms resolved quickly, leaving no residual neurologic deficits.
A control transcranial Doppler showed restored flow with a minor velocity increase at the level of the proximal basilar artery (mean flow velocity: 68.3 cm/sec), probably an expression of residual stenosis (Figure ). On the following day, the patient underwent magnetic and angiomagnetic resonance imaging, which did not show any parenchymal or vessel abnormality. Then a transcranial Doppler was performed and normal blood flow velocities were documented (Figure ).


A 42-year-old overweight woman from rural Greece visited the local physician in February 1997 reporting several episodes of mild upper abdominal pain during the previous three years, not related to food consumption. The pain was not observed elsewhere on the body nor was it correlated with other symptoms, such as fever, nausea or vomiting. In addition, the pain did not affect food intake or daily physical activity. Before medical consultation no systematic treatment had been applied for the pain, which was relieved after some minutes, only to relapse some days later.
History revealed an episode of reported angina 4 months prior to consultation, with non -specific ST/T abnormalities in the ECG. Physical examination revealed no important findings. The blood tests revealed no obvious pathology, with a normal hematocrit and blood coagulation parameters. Biochemical testing for hepatic and renal was also within normal values. Imaging included a chest radiography, which revealed no abnormalities and an abdominal CT scan with oral gastrografin intake, which revealed a 3 × 6 cm cystic formation located at the lower pole of the spleen (Figure ). Due to the lack of an infectious (no compatible clinical signs, no CRP or WBC count elevation, negative serological testing for Echinococcus) or traumatic background and the lack of evidence in favor of a cystic neoplasm (homologous content, normal perimeter, no increase in cancer-associated biochemical markers, such as Ca 19-9 and CEA), a latent congenital epithelial cyst was considered most probable. Four days later an MRI examination confirmed the previous result. The symptoms were not definitely associated to the cyst and the physician related them to the patient's increased stress, assuming she had irritable bowel syndrome.
Eight years later (2005), the patient visited her physician, reporting a periodic continuation of the abdominal pain, whereas neither the character nor the frequency of episodes differed. At this point, she was referred to the Attikon University Hospital for surgical treatment. An abdominal CT scan was performed as part of the preoperative evaluation, revealing a 3 × 5 cm splenic cyst which confirmed the existence of this random finding (Figure ). The rest of the tests were within normal limits again. The patient decided to follow a conservative approach and re-evaluation at an annual basis. In November 2006, an ultrasound of the area revealed further regression of the cyst with a clear hyperechogenic perimeter, the size being estimated at less than 3 cm. For a more accurate description, an MRI scan was performed, which showed almost complete regression, with a remnant lesion of 1.8 × 1.4 cm and low T2 sign in the peripheral border (Figure ), consistent with the pattern observed in the 2005 MRI (a comparative presentation of original and subsequent lesion is provided). Her last MRI examination in 2008 revealed the cyst dimensions equal to the last two radiographic images and a periodically regression of her nonspecific symptomatology, which finally proved that the presence of the cyst was responsible for her previous symptoms.
Surprisingly, in our case, the cyst, although particularly large, was only reported to cause mild symptoms though were not definitely linked to the finding itself, which may imply that former empirical treatment rules may not be applicable in all such cases after all.


The proband, a Caucasian 15-year-old male, is the only child of healthy, non-consaguineous parents. Family history was unremarkable and pregnancy was uneventful. He was born at the 36th week of pregnancy, with a weight of 2120 g (10th-25th centile) and a length at 44 cm (10th centile).
He has never crawled on four limbs but achieved independent walking at the age of 11 months, showing a wide-based, awkward gait with stiffness in lower limbs and difficulty to begin ambulation after a prolonged rest. In the first two years of life, he suffered from two febrile seizure episodes (the EEG findings were normal) and presented language delay (he spoke 10-15 words at 4 years). Since then he started language therapy with appreciable results. A neurocognitive assessment was performed at 4 years and 4 months of age showing a normal range of intelligence (median IQ score on the WPPSI was 95). He attended school with special education needs because of difficulties in reading and writing. At 5 years, extensive investigations were performed: cerebral MRI, echocardiogram, ophthalmological examination and audiometric test were all normal. The electromyography (EMG) revealed the presence of typical myotonic runs (EMG performed in his parents was normal). The serum Creatine Phosphokinase (CPK) was elevated above the normal range (382 U/L, with normal levels being below 270 U/L) in only one occasion, at the age of two years, and reached normal values in the two following measurements. A chest X-ray revealed the presence of dorso-lumbar scoliosis. The thyroid hormonal levels were normal. Muscular biopsy at 5 years revealed mild myopathic change and type I fibers hypotrophy. The FRAXA molecular analysis was negative. He became toiled trained at the expected age. At the age of 7 years he underwent treatment with dyphenilhydantoine for 12 months (the mean dosage was 100 mg/day) but no relief of the myotonia was noticed. Moreover at 10 years a surgical correction for left clubfoot was performed. On careful clinical examination at 15 years, the patient weighted 75.5 Kg (>97th centile), his height was 163 cm (25th centile) and his head circumference was 59 cm (+2.7 SD).
He presented only few mild cranio-facial dysmorphisms suggestive for SRS: a relative macrocephaly, a small face with a broad forehead, deep set eyes and micrognathia. These clinical findings were more relevant during the first years of life (Figure ). The palate was high arched and no limb asymmetry was observed. He referred excessive sweating.
During neurological examination, muscle hypertrophy at lower limbs was noticed and myotonia in all four limbs was evident. The boy showed independent walking with lower limb stiffness and weakness; the muscle strength was normal, the Gower's sign was negative; deep tendon reflexes were weak in the upper limbs and brisk in the lower limbs with ankle increased tone.
Proband's DNA was screened for CLCN1 mutations together with his non-consanguineous parents, after obtaining signed informed consent. Genomic DNA was extracted from the whole blood of the patient and his parents using the BioRobot EZ1 automated purification (QIAGEN). Sequence analysis of muscle chloride channel (CLCN1) gene on the proband's DNA, showed homozygosity for a G to A transition (c.1063G>A), leading to p.G355R mutation, previously characterised as caused by another nucleotide modification (Figure ). The mutated allele was segregating only from the mother (heterozygous for the p.G355R mutation) while no mutated allele was detected in the father. Non paternity was immediately excluded using a panel 15 highly polymorphic markers and one marker for amelogenin (AmpFlSTR identifiler). Furthermore, chromosome 7 markers showed an anomalous segregation within the family suggesting an uniparental transmission. A set of nine additional polymorphic markers spanning the entire chromosome 7 (D7S641, D7S691, D7S2427, D7S1870, D7S2459, D7S2513, D7S661, D7S636 and D7S2423) were therefore analysed (Figure ). Amplifications were analysed on automated sequencer (ABI 3130 Applied Biosystem). PCR were performed in 15 µL reactions containing 100 ng DNA, 1,5 mM MgCl2, 150 uM of each dNTPs, 150 mM Buffer, 0.15 U Ampli Taq Gold. Thermocycling was performed on a 9700 Applied Biosystems, using the following conditions: an initial denaturation at 95°C for 12 min, followed by 10 cycles each of 94°C for 15 sec, annealing at 55°C for 15 sec and an extension at 72°C for 30 sec, followed by 20 cycles each of 89°C for 15s ec, annealing at 55°C for 15 sec and an extension at 72°C for 30 sec. Finally an extension step at 72°C for 10 min. PCR products were analysed on ABI 3130 XL Gene Mapper (Applied Biosystems). The results unambiguously demonstrated the presence of a maternal isodisomy of the entire chromosome 7 (matUPD7) in the proband (Figure ).


A 79-year-old woman presented with a one-day history of acute onset of right upper abdominal pain. Nausea, and vomiting were also present. The vital signs were normal. Examination revealed a very tender mass in the right upper quadrant of abdomen. Laboratory investigations, including complete blood cell count, and liver function tests were within normal limits.
Abdominal ultrasound (US) examination showed a distended gallbladder, thickened gallbladder wall and fluid collection around the gallbladder. Ultrasonographic Murphy's sign was positive.
No stones were detected by US. Computed tomography (CT) of the abdomen showed that the gallbladder was not within the normal anatomical liver fossa. The wall was thickened, and at one point the integrity of the wall was lost. Fluid collection all around the gallbladder indicated a "floating gallbladder" and well-enhanced curvilinear structure on the right side of the gallbladder indicating cystic duct were also identified. Diffuse edematous smooth thickening of the gastric antral wall was observed which was compatible with secondary inflammation (Figure and ). There were no calculi in biliary system.
The patient underwent laparotomy with a preoperative diagnosis of acalculous cholecystitis with possible gangrene. At laparotomy, the gallbladder was distended, and multiple necrotic areas were observed. It was rotated more than 180 degrees clockwise around its mesentery, and there were no gallstone in gallbladder (Figure ). Cholecystectomy was performed in standard fashion. Histopatology of gallbladder was reported as hemorhagic transmural necrosis. The patient was discharged on second postoperative day.


A 49-year-old man from a North African origin and with a Moroccan nationality presented with a 2-year history of progressive stiffness and painful spasms of his both legs, with recent worsening of his condition over the last few weeks resulting in a considerable difficulty of standing up and walking. There was no past history of diabetes, or other auto-immune diseases. The family history was unremarkable. On admission, the lower limbs were rigid with a flexum of the hips and knees, movements were severely limited and painful, and strength could not be assessed because of rigidity and spasms. A slightly increased tone was noted in his upper limbs, with normal muscular strength and without any movement limitation. No paraspinal or axial contractions were palpated. Sensory examination was normal except for reduced vibration sense in both lower extremities. Deep tendon reflexes were normal in upper limbs. Patellar and Achilles jerks could be elicited markedly. Plantar response was flexor bilaterally. Functionally the patient was unable to walk because of the rigidity in his both legs. He had an intact intellect and there were no other neurologic abnormalities.
Results of routine laboratory tests including full blood count (FBC), serum electrolytes, blood urea nitrogen, creatinine, glucose and liver enzymes were normal. The erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) values were normal. Chest X-rays and abdominal ultrasonography revealed no abnormalities. Magnetic resonance imaging of the whole neuraxis and EEG were also normal. Cerebrospinal fluid examination was unremarkable, there were no atypical cells found on cytopathological analysis. Electromyography of the lower limbs revealed no abnormalities. Serologic testing for HIV, syphilis, viral hepatitis B and C was negative. Anti-mitochondrial antibodies and anti-cytoplasm antibodies were found in the serum, while antinuclear antibodies (ANA) and anti- DNA screening and auto-antibodies to glutamic acid decarboxylase (GAD) were within normal limits. Anti-amphiphysin antibodies test wasn't carried out. With the high suspicion that the clinical case could be a SLS, oral diazepam was administered in high doses (25 mg/day) after which we observed a dramatic remission of the clinical state with marked reduction of the hypertonus and the patient could walk with little aid. The administration of 30 mg of baclofen daily provided relief of symptoms.


A 61-year-old man presented to his general practitioner with a history of a rapidly evolving groin swelling. He recalled a pea-sized lesion in his right groin, which had remained static over the past 40 years. There was no relevant past medical history and the patient remembered no preceding episode of trauma or local irritation.
The lesion increased rapidly in size to a 10.5 × 10 × 6 cm firm, smooth exophytic mass with a shiny reddish surface. The centre was ulcerated discharging pus (). The patient was referred for a surgical opinion.
Computed tomography of the lesion showed a complex cystic structure with fluid and septations containing several foci of calcification (). The lesion was excised under general anaesthetic.
Histological examination showed a macroscopically well-circumscribed, pedunculated, partly ulcerated lesion weighing 406.6 grams. On slicing, a well-circumscribed multilobulated mass with a variegated cut surface including cystic and haemorrhagic areas was apparent (). Four tissue blocks were fixed for analysis.
All the tissue blocks were fixed in formalin and routinely processed for paraffin-embedding. Histological sections were stained with haematoxylin and eosin (H&E). Immunohistochemical studies were carried out using a standard panel of mesenchymal and melanocytic markers. Microscopically, the specimen contained a large spindle cell lesion extending from the dermis into the subcutaneous tissue. A well-defined Grenz zone was apparent away from the ulceration and bundles of interlacing spindle cells surrounding small groups of foamy macrophages were present. A storiform pattern was noted. At the centre of the lesion there were areas of cystic degeneration with focal haemorrhage, cholesterol clefting, and giant cells with focal calcification ().
Immunohistochemical staining was positive for CD68 and factor XIIIa. The spindle cells stained strongly positive for factor XIIIa. Focal positivity with CD31 and SMA was noted. Staining for CD34, desmin, MNF116, S100 protein, and AE1/AE3 negative. The morphological and immunohistochemical features were those of a dermatofibroma showing marked degenerative changes. At three-month follow-up the patient was well with no evidence of recurrence.


Our patient is a 68-year-old white female with a two-year history of progressive dyspnea and a persistent non-productive cough. Past medical history included hypertension, lower extremity neuropathy of unknown etiology, and interstitial cystitis. She had a remote history of tobacco use but no exposures to other toxins. Family history was positive for stroke, diabetes, coronary artery disease, and gastric cancer. Physical exam was normal except for bilateral trace lower extremity edema. No jugular venous distension, heart murmur, or tumor plop was present.
Four months previously, a CT scan of the chest, pulmonary function tests, and a pulmonary angiogram were normal. A sleep study showed no apnea but nocturnal hypoxia prompting a prescription for home O2 at night.
At the time of re-evaluation, a transthoracic echocardiogram (TTE) demonstrated a normal ejection fraction of 60% with normal chamber dimensions but showed a large right atrial mass with high flow velocity around the echodensity. A small patent foramen ovale (PFO) was also present. Estimated pulmonary artery pressure was 44 mmHg. A transesophageal echocardiogram confirmed the large immobile right atrial mass, which involved the IVC. A CT scan revealed a cystic dense mass in the IVC and the right atrium with no evidence of pulmonary emboli or metastases (Figure ). The abdomen and pelvis were negative with no evidence of renal cell carcinoma, which can also present with IVC involvement.
There was mild cerebral atrophy without evidence of intracranial masses on a CT scan of the head. A combined PET (positron emission tomography)/CT scan of the chest showed a partially contrast-enhancing intraluminal mass within the intrahepatic and suprahepatic inferior vena cava extending into the right atrium. There was no extension into the hepatic veins. The mass markedly narrowed the suprahepatic inferior vena cava and right atrium with only a small amount of residual lumen noted medially. There was diffuse heterogeneity of the liver without evidence of mass lesion, suggesting hepatic venous congestion. The PET imaging demonstrated uptake in the tumor mass consistent with malignancy but no evidence of metastatic disease. Magnetic resonance angiography (MRA/MRI) showed that the large mass centered at the confluence of the inferior vena cava and right atrium and extended into the right atrium (Figure ). The mass extended 2.5 cm below the diaphragm. The widest transverse dimension was 4.5 cm and the greatest length obliquely was 5.6 cm. There was collateral venous flow with dilatation of the azygous vein and lumbar collaterals.
A fluoroscopically guided biopsy was preformed and histology revealed spindle shaped cells. Immunostains for smooth muscle actin and desmin were positive and those for melanoma and cytokeratin were negative, consistent with the diagnosis of leiomyosarcoma (Figure ).
Intraoperatively, the tumor was noted to originate from the posterior aspect of the IVC and measured approximately 8 cm in length by 4 cm in width, with the widest part lying within the right atrium. Ten minutes of circulatory arrest was required and the tumor was excised along with a portion of the posterior inferior vena cava. The tumor mass was well demarcated with gross total resection. Of note, tumor margins at the time of resection were negative. The inferior vena cava was then closed primarily from the intraluminal side. Surgical clips were left in place to help identify the target for radiation therapy. In addition, the patient had her PFO surgically corrected. The patient tolerated the procedure well and was weaned from bypass without difficulty.
Postoperatively, the patient received radiation therapy. The patient received a course targeting the resection bed of the origin of her tumor in the inferior vena cava. She was treated with photons of 18 megavolts (MV) at the isocenter at 2 Gray (Gy) per fraction for 25 fractions to a total dose of 50 Gy. This was followed by an additional boost to a small area for an additional five fractions to a total dose 10 Gy. The total dose to the tumor bed was 60 Gy. The patient tolerated the course of radiation well and reported no side effects, such as skin toxicity or gastrointestinal toxicity. There were no breaks during treatment.
Subsequent clinical examinations every 6 months and imaging with yearly CT scans have confirmed that the patient has remained disease free 5 years after treatment.


A 56-year-old Japanese man with biopsy-proven NSCLC was receiving active therapy with irinotecan (60 mg/m2) and cisplatin (60 mg/m2). Previously, the patient had had no significant genitourinary history. The combination of irinotecan and cisplatin was stopped because of persistent neuropenic fever and severe fatigue, and oral gefitinib (250 mg once a day) was initiated. Approximately two weeks later, severe LUTS, fever > 101.5°F and cough were noted. Urinalysis demonstrated fewer than 5 red blood cells/high power field, no white blood cells and no bacteria. Urine culture was negative. Sputum cultures showed chlamydial pneumonia, and the patient was started on moxifloxacin, with immediate improvement of cough but minimal improvement of fever, LUTS and hematuria. Over the next month, these symptoms persisted, together with deterioration of hepatic and renal function. Gefitinib therapy was halted. Empirically, ceftazidime was initiated and fever improved. Two weeks after stopping gefitinib, hepatic and renal function returned to normal. However, LUTS and microscopic hematuria continued despite negative urine cultures. The patient was referred to the Urology Department, and thorough investigation of hematuria (i.e., intravenous pyelography (IVP) assessing the kidneys and ureters and cystourethroscopy) was performed. IVP was normal except for a contracted, thickened bladder wall (Figure. ). Cystourethroscopy revealed a small capacity bladder with erythematous lesions throughout the bladder. Because of the small capacity bladder, hydrodilation was performed. No discrete tumors or bladder calculi were noted. The prostatic urethra was unremarkable without trilobar hypertrophy or a prominent median lobe. Random bladder biopsies were obtained as well as urinary cytological examination. Urinary cytology was negative for malignancy. Histological examination of the bladder biopsies showed areas of denuded mucosa, submucosal edema, increased vascularity and white blood cell infiltration, indicative of hemorrhagic cystitis (Figure. ). The symptoms improved over the ensuing four weeks.


A 24-year-old male had periungual wart of 2 years duration over right ring finger and left middle finger nails []. He was a habitual nail biter. Local anaesthesia was achieved by ring block and local infiltration. A torniquet was applied to minimise blood loss. Electrodesiccation was done as per the standard procedure[] and lesion was curetted. Firm pressure was applied for 5 min. Once the bleeding was controlled, trichloroacetic acid (TCA), 30% solution was applied.
Pressure dressing was applied, which was changed on second and seventh day. Systemic antibiotics and analgesics were prescribed for 7 days. Nail biting was strongly discouraged. After removal of dressing patient was advised to apply povidone-iodine ointment for 5 days. One year follow-up shows no recurrence [].


A 70-year-old man, known only to have dyslipidemia, was admitted to our hospital because of fever associated with fatigue and nausea for 6 h. His medications were atorvastatin and omeprazole. He had no prior history of intravenous drug abuse. On examination, the patient was slightly drowsy but in no acute distress. His vital signs were: temperature 38.7°C, pulse 94 bpm, respiratory rate 20 per min, BP 123/59 mmHg and oxygen saturation 100% on room air. His overall exam was unremarkable. The patient did not have skin rash, signs of meningismus or a cardiac murmur. His laboratory findings were: WBC 7.0×106/L, hemoglobin 132 g/L, platelets 125×106/L, random glucose 16.9 mmol/L, sodium 132 mmol/L, potassium 3.6 mmol/L, bicarbonate 20 mmol/L, serum creatinine 88 micromol/L, ALT 69 U/L, AST 87 U/L and GTP 155 U/L. The rest of his laboratory work-up, including urinalysis, coagulation profile and hepatitis profile, were unremarkable. Chest X-ray was normal. Transthoracic echocardiogram did not show vegetations or valvular lesions. The patient was started on intravenous ceftriaxone and vancomycin. Two days later, two of his blood cultures grew MRSA. His intravenous antibiotic regimen was changed to linezolid and cefipime. The patient finished 2 weeks of this regimen with obvious clinical and laboratory improvement and was discharged home in good condition.


A 26 year old man with a background of Morquio syndrome, was admitted for an elective left total hip replacement. Osteoarthritis of the hips secondary to avascular necrosis of the head of femur bilaterally had been diagnosed. There was no past medical history of note; however review of systems revealed snoring and daytime somnolence, suggestive of obstructive sleep apnoea. Clinical inspection demonstrated a man of short stature, his weight was 63 Kg and height 150 cm, with a large head and short neck, the head appeared to be sitting directly on his thorax. On inspection the thorax had an increased anterior-posterior diameter and kyphosis. Clinical examination including respiratory, neurological and cardiovascular systems were normal. Pulmonary function testing and baseline laboratory tests were normal.
Preoperative airway examination demonstrated bulky soft tissue in the pharynx, grade 2 macroglossia, an enlarged uvula and tonsils, an exuberant gag reflex and a Mallampatti grade II airway. Preanaesthetic neutral and extension cervical x-rays were performed and demonstrated a hypoplastic odontoid process, and widening of the atlanto axial joint upon flexion, the joint measured 3 mm in diameter, the upper limit of normal (figure ). Magnetic Resonance Imaging (MRI) of the cervical spine revealed an intermedullary syrinx extending from the second cervical vertebra spine down to the thoracic spine (figure ), this findings ruled out regional spinal anaesthesia. Based on these findings and after discussion with the patient, an awake fibreoptic intubation for the procedure was planned.


A 30-year-old male presented to us with a history of watering and irritation in both eyes of three days duration. He was diagnosed to have EM minor following an attack of viral fever with skin eruptions on the face, arms and legs along with shallow, aphthous ulcers, one week back. There was no history of any drug intake leading to the fever and occurrence of skin eruptions. The erythrocyte sedimentation rate (ESR) was 42 mm/h and the total white blood count was 12,000 cells/mm3 with predominant neutrophils (72%). Routine urine examination was normal. Blood and urine cultures were negative for bacteria and fungi. Chest X-ray was normal. Antinuclear antibody and rheumatoid factor were negative. He was on oral acyclovir 800 mg five times/day, started by his treating dermatologist, given for a total of seven days.
On examination, he had papular skin eruptions on the face, arms and legs with two shallow painful ulcers in the buccal mucosa []. His best-corrected visual acuity was 20/20 in both eyes. Slit-lamp examination in both eyes revealed multiple coin-shaped epithelial lesions, some showing central clearing [, ]. There was no involvement of the stroma. Corneal sensation (tested with wisp of cotton) was normal. Rest of the anterior segment, intraocular pressures and fundus examination were normal. Confocal microscopy (HRT II, Rostock corneal module, Heidelberg, Germany) showed conglomerates of hyper-reflective epithelial cells corresponding to the coin-shaped epithelial lesions []. The subepithelial nerve plexus, the stroma and endothelium were normal. He was started on oral prednisone, 60 mg/day slowly tapered by 10 mg/day over six weeks along with ocular lubricants (1% carboxymethyl cellulose eye drops, four times a day). The skin and corneal lesions [] resolved over six weeks. Repeat confocal microscopy showed normal epithelial cells, subepithelial nerve plexus, stroma with keratocytes and endothelium.