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1.
J Intensive Care Soc ; 24(3): 328-331, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37744070

ABSTRACT

Emphysematous gastritis is a severe form of gastritis caused by gas-forming infectious organisms and is most frequently encountered in critically unwell patients. Diagnosis rests on the radiographic appearances of air within the gastric wall, which may extend into the portal venous system. Not previously described in the context of neutropenic sepsis, our case involves a 77-year-old patient with emphysematous gastritis who was admitted to the intensive care unit with a neutrophil count of 0.1 × 109/L and managed successfully with conservative treatment. Presenting complaints usually include abdominal pain, nausea, vomiting and occasionally haematemesis, in the context of systemic upset. Predisposing factors may include diabetes and immunosuppression, ingestion of corrosive substances, alcohol abuse, and abdominal surgery. The historical approach to management which previously involved urgent exploratory laparotomy with gastrectomy, has largely been replaced with conservative therapy, including broad-spectrum antimicrobials, gut rest and parenteral nutrition, with improved outcomes. Previously considered a commonly terminal diagnosis with mortality rates as high as 60%, this recent shift in approach to management has contributed to mortality rates being halved. The role of oesophago-gastro-duodenoscopy has not been established and is unlikely to be indicated in every case. Longterm complications may be of concern and include fibrosis and gastric contractures.

2.
Langenbecks Arch Surg ; 408(1): 75, 2023 Feb 02.
Article in English | MEDLINE | ID: mdl-36729157

ABSTRACT

Obstructed defecation syndrome (ODS) is a clinical syndrome manifest as difficulty in faecal evacuation despite no mechanical obstruction. It is the final clinical pathway of a number of anatomical and physiological pathologies they can result in considerable misery to the lives of the patients it afflicts. Herein, the authors seek to breakdown the syndrome into its component parts, looking first at normal pelvic floor anatomy and physiology; followed by each pathological element; clinical features and investigation; individual management and management of the patient as a whole. It must be stated that correction of anatomy is not the sine qua non, as this does not always correlate to improvement of symptoms. There is a complex interplay of all elements, and a holistic approach appreciating the gestalt principle of "the whole is greater than the sum of its parts" is paramount. Causes of pelvic pain (levator ani syndrome, coccygodynia, proctalgia fugax and pudendal neuralgia) do not fall into ODS and are beyond the scope of this paper.


Subject(s)
Defecation , Gastrointestinal Diseases , Humans , Defecation/physiology , Constipation/diagnosis , Constipation/etiology , Constipation/therapy , Syndrome , Rectocele/complications
3.
EClinicalMedicine ; 32: 100715, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33681737

ABSTRACT

BACKGROUND: Tuberous Sclerosis Complex (TSC) is a genetic disorder characterised by the development of benign tumours secondary to loss of inhibitory regulation of the mTOR (mechanistic Target of Rapamycin) intracellular growth pathway. Metformin inhibits the mTOR pathway. We investigated whether metformin would reduce growth of hamartomas associated with tuberous sclerosis complex. METHODS: In this multicentre randomized, double-blind, placebo-controlled trial, patients with a clinical diagnosis of tuberous sclerosis, aged over 10 years and with at least one renal angiomyolipoma of greater than 1 cm in diameter were enrolled. Participants were randomly allocated (1:1) by a secure website to receive metformin or placebo for 12 months. The primary outcome was percentage volume change of renal angiomyolipomas (AML) at 12 months compared to baseline. Secondary outcomes were percentage change at 12 months from baseline in volume of cerebral Subependymal Giant Cell Astrocytomas (SEGA); appearance of facial and ungual hamartomas; frequency of epileptic seizures; and adaptive behaviour. The trial is registered with The International Standard Randomised Controlled Trial Number (ISRCTN), number 92545532, and the European Union Drug Regulating Authorities Clinical Trials (EUDRACT), number 2011-001319-30. FINDINGS: Between 1 November 2012 and 30 September 2015 72 patients were screened and 55 were randomly assigned to metformin (28) or placebo (27). Four participants withdrew between randomisation and starting treatment. All 51 patients who started therapy completed the trial and were assessed for outcome at 12 months. The median percentage change in angiomyolipoma (AML) volume was +7.6% (IQR -1.8% to +42.6%) for the placebo group and +8.9% (IQR 1.3% to 19.5%) for the metformin group (p = 0.28). Twenty-seven patients had SEGAs: 13 received placebo and 14 metformin. The median percentage change in SEGA volume was +3.0% (IQR -22.8% to +27.7%) for the placebo group and - 20.8% (IQR - 47.1% to - 5.0%) for the metformin group (p = 0.03). Twenty-one patients were assessed for seizure frequency: 9 received placebo and 12 received metformin. In the metformin group, a mean reduction of 43.7% from baseline in seizures was observed and in the placebo group a 3.1% mean reduction was observed, with a difference in response of 40.6% (95% CI -3.1% to +84.2%, p = 0.03). There were no significant differences between metformin and placebo groups for the other secondary outcomes. There were no deaths. Three serious adverse events (SAEs) occurred during the trial (all patients on metformin). INTERPRETATION: Metformin did not reduce AML volume. Metformin did reduce SEGA volume and seizure frequency compared with placebo. There may be a role for metformin in slowing or reversing growth of some life-threatening hamartomas in TSC and for reducing seizure frequency. Further study is justified. FUNDING: This study was funded by the National Institute for Health and Research (NIHR) through the The Research for Patient Benefit Programme (RfPB).

4.
Dev Med Child Neurol ; 59(6): 612-617, 2017 06.
Article in English | MEDLINE | ID: mdl-27935023

ABSTRACT

AIM: The causes of death in patients with tuberous sclerosis complex (TSC) have rarely been studied, with only one published account, which was reported from the Mayo Clinic in 1991. We aimed to investigate mortality in a large cohort of patients with TSC from one of two national referral clinics in the UK. METHOD: We identified 284 patients who attended Bath TSC clinic between 1981 and 2015, and ascertained causes of death by reviewing medical records, death certificates, and postmortem reports. RESULTS: Sixteen patients died from complications of TSC: eight from TSC kidney diseases; four from sudden unexpected death in epilepsy (SUDEP); two from lymphangioleiomyomatosis; one from a subependymal giant cell astrocytoma; and one from a pancreatic malignancy. The median age of death was 33 years (interquartile range [IQR] 26-46). Mortality was significantly more common in patients with learning disabilities than in those without (13/135 [9%] vs 3/131 [2%]; two-tailed Fisher exact test p=0.020). INTERPRETATION: Renal disease is a major cause of mortality in TSC. Lifelong surveillance and early intervention is warranted. SUDEP is also an important cause of mortality. Patients with learning disabilities are at significantly greater risk of early mortality and this implies the need for greater vigilance for TSC-related complications in this group. Female patients are vulnerable to pulmonary and renal disease. Pancreatic lesions are a rare but potentially treatable cause of mortality.


Subject(s)
Tuberous Sclerosis/mortality , Adolescent , Adult , Aged, 80 and over , Cause of Death , Cohort Studies , Databases, Factual , Epilepsy/complications , Epilepsy/mortality , Female , Follow-Up Studies , Humans , Kidney Diseases/complications , Kidney Diseases/mortality , Learning Disabilities/complications , Learning Disabilities/mortality , Male , Middle Aged , Tuberous Sclerosis/complications , United Kingdom , Young Adult
5.
Transplantation ; 85(11): 1663-7, 2008 Jun 15.
Article in English | MEDLINE | ID: mdl-18551076

ABSTRACT

Patients waiting more than 3 years for a renal transplant were ranked according to our novel Bristol and Region Allocation by Non-heart beating Donor Score (BRANDS). One kidney from 40 non-heart beating donors was allocated to the highest BRANDS long-waiter and the other kidney allocated according to the UK National Allocation Scheme (NAS). The scheme reduced the number of patients waiting more than 3 years by 20%. Despite longer dialysis time, greater sensitization and more human leukocyte antigen mismatches, BRANDS patients had equivalent 3-year graft survival (BRANDS 91%, NAS 97%, P=0.264) and patient survival (BRANDS 94%, NAS 92%, P=0.99). Results were similar to 242 synchronous recipients from heart-beating donors. Renal function was significantly lower in BRANDS recipients (40 vs. 62 mL/min/1.73 m2, P<0.0001). Transplanting long-waiting patients with kidneys from non-heart beating donors has reduced waiting times without compromising early outcomes. It is unclear if equivalent survival will be sustained in the long term.


Subject(s)
Kidney Transplantation/methods , Tissue Donors , Tissue and Organ Procurement/methods , Waiting Lists , Death , England/epidemiology , Female , Follow-Up Studies , Graft Rejection/epidemiology , Humans , Incidence , Kidney Transplantation/mortality , Male , Middle Aged , Prognosis , Retrospective Studies , Survival Rate
6.
Transplantation ; 83(12): 1635-8, 2007 Jun 27.
Article in English | MEDLINE | ID: mdl-17589348

ABSTRACT

Presently, sirolimus (rapamycin) is used as both induction and maintenance immunosuppression in solid organ transplants, including whole pancreas and kidney, and islet transplantation. Sirolimus has been suggested to have deleterious effects on islet beta-cell and renal function. We investigated the effect of sirolimus on the viability of islets, podocytes, and renal tubular cells. Sirolimus reduced the viability of islets and HK-2 human proximal renal tubular cells in vitro. This toxic effect was associated with a reduction of vascular endothelial growth factor (VEGF) release by islets but not the proximal tubular cells. Sirolimus reduced both viability and VEGF production by murine beta-cells, and blockade of VEGF-164 was associated with a reduction in viability. Transfection of murine islets with adenoviral VEGF-165 improved islet viability. These data are consistent with the hypothesis that sirolimus is toxic to islets and beta-cells by blockade of VEGF-mediated survival pathways.


Subject(s)
Islets of Langerhans/metabolism , Kidney/metabolism , Sirolimus/toxicity , Vascular Endothelial Growth Factor A/metabolism , Animals , Cell Line , Cell Survival/drug effects , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Islets of Langerhans/drug effects , Kidney/drug effects , Mice , Mice, Inbred C57BL
7.
Transpl Int ; 20(2): 156-66, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17239024

ABSTRACT

The performance of multidetector computed tomography (CT) angiography was assessed in the pre-operative evaluation of live renal donors. Between July 1998 and March 2006, 156 consecutive patients underwent open donor nephrectomy following pre-operative multidetector CT angiography (MDCTA). Operative notes were compared with radiological reports and discrepancies identified. MDCTA missed five of 28 accessory arteries (four visible with hindsight), accuracy of 96%. Of 30 early-branching renal arteries, eight were missed (all visible with hindsight), accuracy 95%. MDCTA missed only one of 13 venous anomalies (accuracy 97%) and also missed the only duplicated collecting system: both were undetectable with hindsight. Following modifications to image acquisition and interpretation sensitivity, negative-predictive value and accuracy were significantly increased. The results were compared with pooled data from published studies of live donor imaging. This study and previous studies of MDCTA had improved sensitivity for arterial and venous anomalies over single detector CT angiography and MR angiography. We conclude that multidetector CT angiography is an accurate modality in the pre-operative evaluation of live renal donors. Regular communication between the transplant surgeon and the radiologist is paramount to improve reporting of surgically relevant anatomy. Mechanisms should exist for auditing and improving pre-operative imaging in any live donor programme.


Subject(s)
Kidney Transplantation , Kidney/blood supply , Living Donors , Renal Artery/diagnostic imaging , Renal Veins/diagnostic imaging , Adult , Aged , Angiography/methods , Female , Humans , Kidney/diagnostic imaging , Kidney/surgery , Male , Middle Aged , Tomography, X-Ray Computed/methods
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