Characterization of the iron-binding site in mammalian ferrochelatase by kinetic and Mössbauer methods.

All organisms utilize ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) to catalyze the terminal step of the heme biosynthetic pathway, which involves the insertion of ferrous ion into protoporphyrin IX. Kinetic methods and Mössbauer spectroscopy have been used in an effort to characterize the ferrous ion-binding active site of recombinant murine ferrochelatase. The kinetic studies indicate that dithiothreitol, a reducing agent commonly used in ferrochelatase activity assays, interferes with the enzymatic production of heme. Ferrochelatase specific activity values determined under strictly anaerobic conditions are much greater than those obtained for the same enzyme under aerobic conditions and in the presence of dithiothreitol. Mössbauer spectroscopy conclusively demonstrates that, under the commonly used assay conditions, dithiothreitol chelates ferrous ion and hence competes with the enzyme for binding the ferrous substrate. Mössbauer spectroscopy of ferrous ion incubated with ferrochelatase in the absence of dithiothreitol shows a somewhat broad quadrupole doublet. Spectral analysis indicates that when 0.1 mM Fe(II) is added to 1.75 mM ferrochelatase, the overwhelming majority of the added ferrous ion is bound to the protein. The spectroscopic parameters for this bound species are delta = 1.36 +/- 0.03 mm/s and delta EQ = 3.04 +/- 0.06 mm/s, distinct from the larger delta EQ of a control sample of Fe(II) in buffer only. The parameters for the bound species are consistent with an active site composed of nitrogenous/oxygenous ligands and inconsistent with the presence of sulfur ligands. This finding is in accord with the absence of conserved cysteines among the known ferrochelatase sequences. The implications these results have with regard to the mechanism of ferrochelatase activity are discussed.

Comparison of hand injection with mechanical injection for digital subtraction selective cerebral angiography.

100 patients undergoing digital subtraction cerebral angiography were randomized to have contrast delivered by either hand or mechanical injection. We compared the two modes of injection for image quality, the presence of vertebral reflux, possible complications and radiation exposure to the radiologist. There was no statistical difference between the two modes of contrast delivery for image quality and vertebral reflux. Only one definite temporary neurological complication was recorded. However, radiation exposure to the radiologist's hand and body were reduced by up to 70% by using a mechanical injector for contrast delivery during selective cerebral angiography with digital subtraction. We advocate use of the mechanical injector by radiologists who perform regular angiography to reduce their exposure to radiation.

The role of epidural fibrosis and defective fibrinolysis in the persistence of postlaminectomy back pain.

Clinical features, contrast-enhanced lumbar tomographic findings, and biochemical plasma fibrinolytic parameters were critically assessed in 70 patients suffering severe, chronic postsurgical low-back and radicular pain to determine the cause of their persisting symptoms. Patients exhibited gross functional disability and significant impairment of plasma fibrinolytic activity, compared with 84 normal control subjects. This fibrinolytic defect appeared attributable to disproportionate increases in circulating plasminogen activator inhibitor-1 levels. Clinical features were slightly worse in patients with radiologic epidural fibrosis, whereas the frequency of radiologic abnormalities, including epidural fibrosis, was higher in patients with fibrinolytic abnormalities. The results, however, demonstrated no significant associations between patients' symptoms and signs and their biochemical and radiologic abnormalities.

Paediatric medulloblastoma: atypical CT features at presentation in the SIOP II trial.

A review of cranial CT studies of 233 patients for the Second Medulloblastoma Trial of the International Society of Paediatric Oncology showed "typical" CT appearances in only 30% of patients. The varied appearances encountered are described with particular emphasis on atypical CT features.

The value of soft tissue signs in wrist trauma.

A retrospective study of the wrist radiographs of 1453 patients presenting with acute wrist trauma was undertaken in order to assess the value of soft tissue signs. A total of 773 radiographs which were judged to be normal were used to evaluate the normal pronator quadratus fat stripe. The distance of the normal pronator fat stripe from the radius was shown to be significantly lower in females than in males and increased with age. The increase with age was greater in males. Although most fractures were associated with some soft tissue abnormality, certain fractures, especially greenstick fractures in children, had normal soft tissue planes. Only 4% of the wrists examined had soft tissue abnormalities with no visible fracture. The presence of soft tissue signs should therefore be considered with suspicion when evaluating wrist radiographs in trauma, but the absence of signs does not necessarily exclude a fracture.

Computed tomographic myelography in the investigation of childhood scoliosis and spinal dysraphism.

The combined investigations of positive contrast myelography and computed tomographic (CT) myelography were performed on 53 consecutive children. Thirty-eight (72%) of these investigations were performed as a routine pre-operative procedure to identify occult spinal dysraphism in patients with childhood scoliosis; the remainder were because of the "orthopaedic syndrome", cervical radiculopathy, back pain and patients with clinical findings to suggest spinal dysraphism. In the 20 patients (38%) with idiopathic scoliosis, there was no case of spinal dysraphism and CT myelography provided no additional information to the myelogram. In the seven patients with spinal dysraphism the plain radiographic abnormalities identified were lumbar vertebral abnormalities (five), thoracic vertebral abnormalities (one), and sacral agenesis (one). Diastematomyelia was found in four patients, a low tethered cord and lipoma in two patients and a large lipoma in one patient. In all of these cases the myelogram indicated the intraspinal abnormalities; however, CT myelography provided more precise anatomical detail. We conclude that CT myelography is not indicated in the initial preoperative assessment of idiopathic scoliosis but should be reserved for patients with congenital or complicated scoliosis where the association with dysraphism is well recognised.

Fracture of the sella turcica: a report of three cases.

Fractures of the sella turcica are rare. Recognition of fractures in this area is very important as serious immediate and delayed neurological, endocrine and vascular complications may occur. Most of these patients will develop at least one cranial nerve palsy; a significant number will develop hypopituitarism and a few will develop local vascular abnormalities.

Intraventricular blood without parenchymal clot following spontaneous subarachnoid haemorrhage.

The position of an intracerebral haematoma shown on computerised tomography (CT) of patients who have suffered a recent spontaneous subarachnoid haemorrhage is a powerful indicator of the source of the bleed. In the absence of such a parenchymal clot, does the distribution of intraventricular blood have similar predictive value? The scans of 22 patients showing intraventricular blood without parenchymal clot were compared with subsequent angiographic appearances. The distribution of intraventricular blood does not appear to correlate with either the clinical status of the patient, or the nature, site or size of the bleeding lesion.

Is routine computerised axial tomography in epilepsy worth while?

The value of routine computerised axial tomography of the brain (CT scanning) was assessed in 220 consecutive patients with epilepsy or isolated seizures. Abnormal CT scans were found in more than half the patients with focal seizures associated with focal signs or a delta focus on the electroencephalogram (EEG). In patients without focal features the CT scan was normal in 94%. Only a quarter of the abnormalities found on CT scanning were potentially treatable by surgery, and only 10% of all the patients had their management changed as a result of CT scanning. In 3 patients with tumours the first scan had been normal. Careful clinical assessment and examination supported by an EEG remain of paramount importance in the management of epilepsy, and CT scanning should be reserved for patients with focal features.

Spontaneous periodic hypothermia with lipoma of the corpus callosum.

A patient with spontaneous periodic hypothermia who had both a lipoma and agenesis of the corpus callosum is described. Spontaneous periodic hypothermia associated with corpus callosum abnormalities is a distinct entity and although the mechanism underlying the hypothermic episodes is unexplained, the term "diencephalic autonomic epilepsy" does not seem appropriate.

Computed tomography of abdomen in staging and clinical management of lymphoma.

During July 1976 to Demember 1977, 150 patients with Hodgkin's disease and 138 with non-Hodgkin's lymphoma were examined by computed tomography (CT). In 45 cases 50 repeat examinations were conducted. Concurrent laparotomy and lymphography were performed on 68 and 56 patients respectively. The overall incidence of false-positive CT examinations as confirmed by laparotomy was 7.4%. In 18 patients with non-Hodgkin's lymphoma in the abdomen there was good correlation between the two techniques. Of the 50 patients with Hodgkin's disease who underwent laparotomy, 17 had splenic disease and 14 minimally enlarged lymph nodes in 20 areas; CT, however, detected only four diseased spleens and five minimally enlarged lymph nodes. Nevertheless, CT often detected enlarged lymph nodes missed by lymphography and was 23% more efficient than lymphography in detecting unsuspected disease. CT also detected unsuspected disease in patients with relapse of lymphoma. CT may replace other non-invasive investigations of abdominal disease in patients with lymphoma and give a reliable guide to prognosis. It does not, however, eliminate the need for laparotomy in staging Hodgkin's disease.

A clinical evaluation of isotope scanning, ultrasonography and computed tomography in pancreatic disease.

In a prospective study of 46 patients with suspected pancreatic disease the provisional diagnoses arrived at independently by isotope scanning (IS), ultrasonography (USS) and computed tomography (CT) have been compared. In the control group, IS and CT were associated with a higher false positive rate than USS; The isotope scan was abnormal in most patients with proven chronic pancreatitis and cancer. The results from USS and CT were similar when structural changes were present. USS was superior in diagnosing pancreatic carcinoma and was a convenient means to follow the progression of acute pancreatitis to final resolution or the development of a pseudocyst. CT proved especially useful in accurately delineating cysts, pseudocysts and calculi prior to planning surgery and in assessing disease in contiguous viscera.

Computed tomography in the evaluation of the solitary or unilateral nonfunctioning kidney.

Computed tomography (CT) using the EMI CT5000/5005 scanner was performed on 14 patients with a solitary functioning kidney demonstrated by other radiological investigations. Examinations before and after intravenous injection of contrast material have been undertaken. In the majority of cases, the patients were referred as a "nonfunctioning kidney" following excretion urography. Other referrals included previous nephrectomy or solitary kidneys. In all cases, the CT scan made possible the definitive diagnosis. The diagnosis included unsuspected hydronephrosis, vestigial kidney, contracted kidney secondary to chronic pyelonephritis and calculus, recurrence of a hypernephroma, and lymphomatous infiltration. Valuable information was obtained about the vascular pedicle, the renal collecting systems, the perinephric space, and the retroperitoneal space including the paraaortic lymph nodes. Furthermore, the increased sensitivity of the technique in detecting lower concentrations of iodine provided information regarding renal function. It is concluded that the noninvasive nature of CT makes it a valuable adjunct in the further investigation of such patients.

Computed tomography in the diagnosis of diseases of the paranasal sinuses.

The authors investigated 31 patients suffering from benign and malignant lesions of the paranasal sinuses. Clinical, conventional radiological methods and computed tomography were used. In benign lesions CT added little significant information to that obtained by conventional radiological methods. In malignant lesions, however, CT provides additional valuable information. It gives a clear picture of the posterior, superior and orbital extent of paranasal tumours. It also shows the extent of the tumour into the infratemporal fossa.

Computed tomography, ultrasound, and cholestatic jaundice.

Computed tomography detected the presence of dilated ducts in 15 of 18 cases with extrahepatic obstructive jaundice and demonstrated the obstructing lesion in 18 out of 25. The cause of the obstruction was detected in the absence of duct dilatation, and calculi which were radiolucent on conventional radiographs were demonstrated. Ulstrasound detected dilated ducts in eight of 10 cases, but demonstrated the cause of the obstruction in only one of 13 cases. Both techniques are capable of demonstrating dilated ducts in the majority of cases, but computed tomography is better at detecting the cause of the obstruction.

Computed tomographic scanning in liver disease.

The non-invasive diagnostic technique of computed tomograph (CT) has been assessed in 100 patients with established liver disease. CT can differentiate extra- from intrahepatic cholestasis and may define the obstructing lesion in the former group. It is of value in detecting infiltrations with fat or iron, and provides useful information in patients with cirrhosis and metastatic deposits. At present it appears of less value in the diagnosis of non-fibrotic parenchymal liver disease.

Suprapubic micturating cystourethrography in infants.

Contrast medium may be safely and easily placed in the bladder by suprapubic puncture. Samples of clean urine may be obtained at the same examination. The technique and its advantages are described in detail.

Computed tomography in syringomyelia and the associated Arnold-Chiari type I malformation.

A total of 20 patients with an Arnold-Chiari Type I malformation, i.e. without skeletal abnormality and associated with a syringomyelic syndrome, were studied using the EMI Whole Body Scanner CT5000. Two groups were considered: (i) a retrospective series of 12 patients without intrathecal water soluble contrast media and (ii) a prospective series of eight patients after the introduction of intrathecal Metrizamide. In the first group tonsillar herniation could not be conclusively identified on CT and cord visualisation was possible in only two cases. In the second group, tonsillar herniation and cord expansion were consistently demonstrated. Cord cavitation has also been detected. In both groups it was possible to assess the size and position of the ventricular system. The results of this study indicate that evaluation of the upper cervical cord cerebellar tonsillar herniation, may be achieved, but only following opacification of the CSF. The precise extent of cerebellar tonsillar herniation may be difficult to evaluate. The reasons for these findings are discussed.

Small bowel melaena: 2 cases diagnosed by angiography.

Two cases of small bowel tumour presenting with melaena are reported. Selective visceral arteriography was found to be invaluable in the management of these cases. The first case presented with intermittent bleeding causing anaemia. Conventional barium studies of the small and large bowel revealed no abnormality. Superior mesenteric angiography revealed a mass lesion in the jejunum, with features characteristic of a leiomyoma. The second case presented with massive gastrointestinal bleeding. Selective visceral angiography was performed initially and revealed a large, mainly avascular, mass lesion in the ileum. Pathological examination showed a leiomyoma which had undergone cystic degeneration. The value of selective angiography in patients with suspected small bowel bleeding is discussed..