Difficulties in localization and treatment of insulinomas in type 1 multiple endocrine adenomatosis (MEA).

A 15 year old girl with a family history of type 1 multiple endocrine adenomatosis presented with reversible neurological disturbances, hypoglycaemia and hyperinsulinaemia. Initial radiology was normal, but portal venous sampling suggested an insulinoma in the tail of the pancreas which was removed with conservation of the spleen. Hypoglycaemia persisted despite high doses of diazoxide and intravenous dextrose. A second laparotomy revealed a pancreatic endocrine tumour and sub-total pancreatectomy was performed. Histology revealed islet cell microadenomatosis. Hypoglycaemia persisted despite treatment with somatostatin analogues and 40% intravenous dextrose was required to maintain normoglycaemia. A possible lesion near the splenic hilum on computed tomographic scan was reported as a splenunculus although further peripheral, hepatic and portal venous sampling suggested hepatic or systemic lesions. A positron emission scan and selective visceral angiography suggested a lesion in the left upper quadrant. Acute lactic acidosis, rhabdomyolysis and renal failure supervened. Post mortem revealed the putative ''splenunculus'' to be a residual insulinoma, whilst the splenic vein was thrombosed, accounting in part for discrepant venous sampling data. Hyperinsulinaemia in type 1 multiple endocrine adenomatosis may require more aggressive surgical and hormonal intervention than when dealing with solitary insulinomas. Insulinomas may mimic developmental abnormalities on computed tomographic scanning.     

Magnetic resonance imaging in young adults with cerebral infarction due to moyamoya

The number, size, and location of cerebral infarctions, and blood flow in the middle cerebral artery as seen on proton magnetic resonance imaging were assessed in six white adults with angiographically documented moyamoya. Findings were correlated with clinical presentation, computed tomography, and angiography. Large hemispheric infarctions were found in five hemispheres, predominantly in watershed regions. Subcortical infarctions (n = 56) were found in all hemispheres. They were predominantly located in the centrum semiovale, in the distal beds of supply of the penetrating branches of the anterior and middle cerebral arteries. Infarction of the putamen was found in three hemispheres, caudate nucleus in four, globus pallidus in two, and anterior limb of the internal capsule in two. There were none in the posterior limb of the internal capsule, thalamus, brain stem, or cerebellum. Middle cerebral artery flow was visualized as a signal-void flow sign in only three hemispheres. Cerebral infarctions due to moyamoya are bilateral, multiple, often small, and asymptomatic, affecting predominantly the carotid circulation in watershed regions. Subcortical infarctions in the centrum semiovale and large hemispheric infarctions in hemodynamically compromised areas are the predominant findings.     

The response of spontaneous and transplantable murine tumors to vasoactive agents measured by 31P magnetic resonance spectroscopy.

31P magnetic resonance spectroscopy has been used to compare the effects of the vasoactive agents hydralazine and flunarizine on the oxygenation of the transplantable tumors, SCCVII/Ha and 16C, and a range of spontaneous mammary tumors arising in the breeding stock in the Genetics Division at the Radiobiology Unit. The vasodilator hydralazine, previously shown to increase the radiobiological hypoxic fraction of transplantable murine tumors, increased inorganic phosphate to total phosphate (Pi/total) in SCCVII/Ha and 16C tumors. However, only two spontaneous tumors responded to this agent (2/12). The calcium antagonist flunarizine, which sensitizes the SCCVII tumor to X rays, consistent with a reduction in hypoxic fraction, reduced Pi/total in this and the 16C tumor. Further, most spontaneous tumors tested (8/10) responded to this agent, as measured by a reduction in Pi/total. These results point to fundamental differences between transplantable and spontaneously arising tumors in mice in their response to vasoactive agents.     

The sonographic appearances in postpartum thyroiditis.

During the postpartum period about 50% of women with circulating thyroid autoantibodies develop a transient autoimmune thyroiditis. To determine the sonographic appearances in postpartum thyroiditis (PPT), serial ultrasound (US) scans of the thyroid were performed in 135 postpartum women who were divided into three clinical groups: Group 1, 37 antibody positive subjects who developed PPT; Group 2, 28 antibody positive subjects in whom thyroid function remained normal; Group 3, 70 antibody negative controls. Thyroid hypoechogenicity was observed in 14/31 patients (45%) who were scanned between 4 and 8 weeks postpartum and who subsequently developed PPT (Group 1) compared with 4/24 patients (17%) in Group 2 (P less than 0.05) and 1/65 patients (1.5%) in Group 3 (P less than 0.001). In antibody positive patients, the positive predictive value of an abnormal scan during this period was 78%. Between 15 and 25 weeks postpartum thyroid hypoechogenicity was present in 32/37 patients (86%) in Group 1 compared with 11/28 patients (39%) in Group 2 (P less than 0.001) and 2/70 patients (3%) in Group 3 (P less than 0.001). Sonographic abnormality persisted beyond 32 weeks postpartum in 36/41 antibody positive patients (87%) who had exhibited thyroid hypoechogenicity earlier during the study and who had late scans. The characteristic US appearance in PPT is thyroid hypoechogenicity. The role of sonography in the prediction, diagnosis and follow up of patients with PPT is discussed.     

Nephrocalcinosis.

The pathogenesis of NC in VLBW infants appears to be multifactorial. The vulnerability of extreme immaturity and the underdevelopment of renal function may be the most important variables. In some ways, we view this problem as similar to that of retinopathy of prematurity. (Clearly the exposure of the retina to high partial pressures of oxygen contributes to the development of retinopathy of prematurity but other variables--some known, such as an immature retina, and others not yet defined--must be present.) Hypercalciuria is common in the VLBW infant, yet not all develop NC. Decreased glomerular filtration rate, low citrate excretion, and frequently an alkaline urine are in part due to the immaturity of renal function of these infants. The need for prolonged hyperalimentation resulting in increased oxalate excretion and the development of BPD frequently requiring diuretics that may cause phosphaturia and magnesium depletion and that may increase calcium excretion are more common in the smallest and sickest of premature infants. Even transient insults to the kidneys, such as hypoxia or hypotension or the use of nephrotoxic drugs that provoke tubular injury and cell death with the probability of crystal formation and growth by way of heterogeneous nucleation, are likely to occur more frequently in this vulnerable population.     

Dual function nitroimidazoles less toxic than RSU 1069: selection of candidate drugs for clinical trial (RB 6145 and/or PD 130908.

Following the toxicity and synthetic difficulties encountered with the hypoxic cell radiosensitizer RSU 1069, efforts have focused on development of a superior analogue. Two compounds, RB 6145 and PD 130908, have emerged from this program which overcome the instability and synthetic problems associated with RSU 1069 while retaining favorable biological activity. Both agents show comparable radiosensitizing activity to RSU 1069 following oral or i.p. administration to mice bearing the KHT or RIF-1 tumors. Sensitizing efficiency is about 10 X greater than that observed for misonidazole or etanidazole. Toxicity toward hypoxic tumor cells in vivo is demonstrated by clamping tumors (for 60 min) following administration of PD 130908 or RB 6145. Both are effective hypoxic cytotoxins, but less potent than RSU 1069. Systemic toxicity is substantially reduced following oral drug administration. Further, doses achievable following fractionated drug treatments are sufficiently high to produce significant levels of radiosensitization.     

A controlled trial of scheduled replacement of central venous and pulmonary-artery catheters.

BACKGROUND. The incidence of infection increases with the prolonged use of central vascular catheters, but it is unclear whether changing catheters every three days, as some recommend, will reduce the rate of infection, It is also unclear whether it is safer to change a catheter over a guide wire or insert it at a new site. METHODS. We conducted a controlled trial in adult patients in intensive care units who required central venous or pulmonary-artery catheters for more than three days. Patients were assigned randomly to undergo one of four methods of catheter exchange: replacement every three days either by insertion at a new site (group 1) or by exchange over a guide wire (group 2), or replacement when clinically indicated either by insertion at a new site (group 3) or by exchange over a guide wire (group 4). RESULTS. Of the 160 patients, 5 percent had catheter-related bloodstream infections, 16 percent had catheters that became colonized, and 9 percent had major mechanical complications. The incidence rates (per 1000 days of catheter use) of bloodstream infection were 3 in group 1, 6 in group 2, 2 in group 3, and 3 in group 4; the incidence rates of mechanical complications were 14, 4, 8, and 3, respectively. Patients randomly assigned to guide-wire-assisted exchange were more likely to have bloodstream infection after the first three days of catheterization (6 percent vs. 0, P = 0.06). Insertions at new sites were associated with more mechanical complications (5 percent vs. 1 percent, P = 0.005). CONCLUSIONS. Routine replacement of central vascular catheters every three days does not prevent infection. Exchanging catheters with the use of a guide wire increases the risk of bloodstream infection, but replacement involving insertion of catheters at new sites increases the risk of mechanical complications.     

Altered gastric emptying in the head-injured patient: relationship to feeding intolerance

Most patients with moderate to severe head injury initially do not tolerate enteral feedings postinjury. This intolerance is more prolonged than that found in patients suffering other types of trauma. The authors prospectively evaluated 12 patients with moderate to severe head injury (Glasgow Coma Scale score between 4 and 10) throughout their hospitalization for liquid gastric emptying as a possible mechanism for intolerance to enteral feeding. During Week 1, the majority of patients displayed a delay in gastric emptying. Patients also displayed an abnormal biphasic response (gastric emptying faster than normal during the early stage but prolonged later). By Week 2, many patients still had delayed and abnormal biphasic responses to gastric emptying. By Week 3, an improvement was observed with the majority of patients exhibiting rapid gastric emptying, but delays and abnormal biphasic responses were still seen. Patients who initially had rapid or normal gastric emptying tolerated full-strength full-rate feedings significantly earlier compared with those who experienced delayed gastric emptying (8.5 +/- 0.5 days vs. 13.7 +/- 3.2 days, p less than 0.001). All patients tolerated full-strength full-rate feedings by Day 16 postinjury (range 7 to 16 days) except the two patients who displayed delayed gastric emptying for prolonged periods of time (mean 25 days). This is the first study to longitudinally evaluate gastric emptying following head injury. The authors suggest that patients with moderate to severe head injury often experience alterations in gastric emptying which may affect their ability to tolerate enteral feedings.