Protoporphyrinaemia and decreased activities of 5-aminolevulinic acid dehydrase and uroporphyrinogen I synthetase in erythrocytes of a Vitamin B6-deficient epileptic boy given valproic acid and carbamazepine

Carbamazepine (CBMZP) has been implicated as an inhibitor of the activities of 5-aminolaevulinic acid dehydratase (ALA-D) and uroporphyrinogen I synthetase (URO-S). In an epileptic boy undergoing long-term treatment with valproic acid (VPA), 1.3 g/d, CBMZP, 0.9 g/d and folic acid, 7.5 mg/d, decreased activities of ALA-D and URO-S coincided with increased levels of erythrocyte protoporphyrin (EP) in the absence of Pb poisoning, iron depletion and erythropoietic protoporphyria. A progressive fall in plasma pyridoxal 5'-phosphate (B6-P) to 7.7 nmol/L (lower reference limit, 14.6 nmol/L) prompted implementation of pyridoxine HCl (B6-HCl), 87.5 mg/d followed by administration of both B6-HCl and preformed B6-P (50 mg/d each). This permitted the eventual withdrawal of VPA and a net reduction of CBMZP to 450 mg/d. During these manipulations, ALA-D and URO-S activities, EP and urinary porphyrins and their precursors were measured serially. An assay system utilizing red cell ALA-D for generation of porphobilinogen (PBG) from added ALA at pH 7.4 was used for determination of ALA-D and URO-S activities in separate aliquots of the same assay mixture both in the absence and presence of Zn and dithiothreitol (DTT). One unit (U) for ALA-D = 1 nmol PBG/L RBC/s; for URO-S = 1 nmol porphyrin/L/s; minimum normal level for ALA-D = 135 U; for URO-S = 6 U. B6-HCl alone entailed increases in ALA-D and URO-S prior to any reduction of CBMZP. After administration of both B6-HCl and B6-P and withdrawal of VPA, the overall increase in ALA-D was from 54.59 to 197.2 U (-Zn; -DTT) and from 50.76 to 217.3 U (+Zn; +DTT). The overall increase in URO-S was from 2.67 to 8.90 U (-Zn; -DTT) and from 3.02 to 8.66 U (+Zn; +DTT). During stepwise reduction of VPA, EP remained elevated to values as high as 2.48 mumol/L (upper reference limit, 1.33 mumol/L). Only after permanent withdrawal of VPA did concentrations of EP fall to normal levels. Values for porphyrins and their precursors in urine were normal throughout. Since both VPA and B6-P are strongly protein-bound, it is suggested that VPA displaced B6-P from protective protein binding sites and that the resulting deficit in B6-P (rather than CBMZP) reduced ALA-D and URO-S activities via primary reduction of ALA-synthetase activity. Increases in EP emerge as a hitherto unappreciated effect of VPA warranting further investigation.     

Diagnostic performance of a computer-based ECG rhythm algorithm

We examined the accuracy of computer-based rhythm interpretation from one electrocardiograph manufacturer (GE Healthcare Technologies MUSE software 005C) in 4297 consecutive recordings in a university hospital setting. Overreading was performed by either of 2 experienced cardiologists, and all disagreements with the initial computer rhythm statement were reviewed by the second cardiologist to achieve physician consensus used as the "gold standard" for rhythm diagnosis. Overall, 13.2% (565/4297) of computer-based rhythm statements required revision, but excluding tracings with pacemakers, the revision rate was 7.8% (307/3954), including 3.8% involving the primary rhythm diagnosis and 3.9% involving definition of ectopic complexes. The false-negative rate for sinus rhythm was only 1.3%, but a computer diagnosis of sinus rhythm was incorrect in 9.9% of other rhythms. The false-negative rate for atrial fibrillation was 9.2%, whereas a computer diagnosis of atrial fibrillation was incorrect in 1.1% of other rhythms, including sinus. Computer diagnosis of paced rhythms remains problematic, and physician overreading to correct computer-based electrocardiogram rhythm diagnoses remains mandatory.     

An indolent case of severe acute respiratory syndrome

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.     

Scleroderma (Progressive Systemic Sclerosis) with Severe Bowel Involvement. Treatment by Extensive Resection of the Small Intestine

Summary: Scleroderma (progressive systemic sclerosis) with severe bowel involvement. Treatment by extensive resection of the small intestine.
A 48-year-old man with previously diagnosed scleroderma with bowel involvement was admitted to hospital with severe malnutrition attributed to malabsorption. Shortly after this, he developed features of intestinal obstruction followed by paralytic ileus.
Due to failure to respond to medical treatment, operation was carried, out. On two occasions adhesions were divided, but the bowel failed to function. At a third operation the proximal half of the small bowel below the duodeno-jejunal flexure was excised. Following this the patient made a good recovery.
Small bowel involvement in scleroderma is discussed. Ma/absorption is probably related to bacterial proliferation in the small bowel secondary to stasis and may be helped by antibiotic drugs. Other disturbances resulting in inability of the bowel to propel its contents may comprise syndromes of obstruction and paralytic ileus. A/though management of scleroderma bowel involvement is usually medical, surgical treatment may be indicated under certain circumstances. It may be life-saving.     

On instabilities of deep learning in image reconstruction and the potential costs of AI

Deep learning, due to its unprecedented success in tasks such as image classification, has emerged as a new tool in image reconstruction with potential to change the field. In this paper, we demonstrate a crucial phenomenon: Deep learning typically yields unstable methods for image reconstruction. The instabilities usually occur in several forms: 1) Certain tiny, almost undetectable perturbations, both in the image and sampling domain, may result in severe artefacts in the reconstruction; 2) a small structural change, for example, a tumor, may not be captured in the reconstructed image; and 3) (a counterintuitive type of instability) more samples may yield poorer performance. Our stability test with algorithms and easy-to-use software detects the instability phenomena. The test is aimed at researchers, to test their networks for instabilities, and for government agencies, such as the Food and Drug Administration (FDA), to secure safe use of deep learning methods.     

Feasibility of full-thickness gastric resection using master and slave transluminal endoscopic robot and closure by overstitch: a preclinical study

Background

Gastric submucosal tumors are often treated by laparoscopic wedge resection. This study aimed to examine the feasibility of gastric full-thickness resection through a totally endoscopic approach using the master and slave transluminal endoscopic robot (MASTER), and closure of the luminal defect with an endoscopic suturing device.

Methods

The operation was performed in two live porcine models under general anesthesia. First, the anterior wall of the stomach was slung to the abdominal wall using a percutaneous suturing device. An imaginary 5-cm lesion was marked using a needle knife. After the initial mucosal incision was made using an IT knife, the MASTER was introduced through a long overtube. A circumferential mucosal incision was completed with the MASTER to expose the muscularis propria which was grasped and incised to the serosal layer by electrocautery applied through the hook of the MASTER. The full-thickness resection of the gastric wall was completed with retraction using the grasper and dissection using the hook. While the defect was being created, the luminal space was maintained with traction of the percutaneous sutures. The defect was closed with suture plication using an Apollo Overstitch device.

Results

Two full-thickness gastric resections were performed in two nonsurvival porcine models (body weight = 30 and 35 kg, respectively) using the MASTER. The total procedure time was 56 min for the first model and 70 min for the second model. The luminal view was maintained during the whole procedure, and there was no damage to surrounding organs throughout the whole procedure. The gastric defects were closed successfully using Overstitch, with satisfactory gastric distension and no gas leakage afterward.

Conclusion

The current experiment demonstrated the feasibility and safety of a totally endoscopic approach for the treatment of gastric submucosal tumors: full-thickness resection with the MASTER and successful closure of the defect using Overstitch.     

In vivo tissue engineering of an adipose tissue flap using fat grafts and Adipogel

For decades, plastic surgeons have spent considerable effort exploring anatomical regions for free flap design. More recently, tissue‐engineering approaches have been utilised in an attempt to grow transplantable tissue flaps in vivo. The aim of this study was to engineer a fat flap with a vascular pedicle by combining autologous fat grafts and a novel acellular hydrogel (Adipogel) in an established tissue‐engineering model comprising a chamber and blood vessel loop. An arteriovenous loop was created in the rat groin from the femoral vessels and positioned inside a perforated polycarbonate chamber. In Group 1, the chamber contained minced, centrifuged autologous fat; in Group 2, Adipogel was added to the graft; and in Group 3, Adipogel alone was used. Constructs were histologically examined at 6 and 12 weeks. In all groups, new tissue was generated. Adipocytes, although appearing viable in the graft at the time of insertion, were predominantly nonviable at 6 weeks. However, by 12 weeks, new fat had formed in all groups and was significantly greater in the combined fat/Adipogel group. No significant difference was seen in final construct total volume or construct neovascularisation between the groups. This study demonstrated that a pedicled adipose flap can be generated in rats by combining a blood vessel loop, an adipogenic hydrogel, and a lipoaspirate equivalent. Success appears to be based on adipogenesis rather than on adipocyte survival, and consistent with our previous work, this adipogenesis occurred subsequent to graft death and remodelling. The regenerative process was significantly enhanced in the presence of Adipogel.