Trophic effects of unsulfated cholecystokinin on mouse pancreas and human pancreatic cancer.

The effect of unsulfated cholecystokinin on pancreatic growth was evaluated in two experimental models in vivo and in vitro. Mice were injected with sulfated cholecystokinin (CCKs) or unsulfated cholecystokinin (CCKu) (10 or 20 micrograms/kg) or vehicle twice daily for 15 days. Animals were then killed and pancreatic weights, protein, amylase, and DNA content were evaluated. In vitro, growth was evaluated by DNA synthesis and viable cell counts. MIA PaCa-2 and BxPC-3 human pancreatic cancer cells were treated with CCKs or CCKu (10(-12) to 10(-9) M) for 48 or 72 h in the presence of [3H]thymidine to evaluate DNA synthesis. Viable cell counts were performed on both cell lines grown in the presence or absence of unsulfated CCK (10(-12) to 10(-9) M) for 96 h. Pancreatic weight, protein, amylase, and DNA were significantly increased in animals treated with either CCKs or CCKu. However, pancreatic weight, protein, and amylase were significantly higher in mice treated with CCKs compared to CCKu (p less than 0.005). DNA content and index of hyperplasia were the same whether mice were treated with CCKs or CCKu. CCKu was as potent a stimulus for DNA synthesis as CCKs in MIA PaCa-2 and BxPC-3 cells. Finally, CCKu increased cell counts in both pancreatic cancer cell lines. These data suggest that the mechanisms responsible for CCK-induced growth of normal pancreas and pancreatic cancer may differ from those that regulate secretion.     

Depression, dementia, and reversible dementia.

This article reviews the syndromic concepts of depression and dementia and the concurrence of these common entities. In DAT, depression appears to be a reversible source of excess disability, amenable to pharmacologic as well as environmental interventions. In the vascular dementias, depression appears to be a specific complicating feature, in which localization of the lesion plays a significant role. The abulic state should not be mistaken for a depressive syndrome, although its presence should alert the clinician to evaluate for dementia and depression. Depression is especially prevalent in the subcortical dementias. Future studies using dynamic neuroimaging will help define the limits of this important concept. Reversible forms of dementia are much less common than previously suspected. The clinician's task is to identify causes of excess disability due to superimposed illnesses while avoiding diagnostic or therapeutic nihilism. The appropriate use of medication and the ongoing surveillance for adverse drug reactions are the foremost tasks of today's clinician treating the elderly patient.     

Method for the quantitative assessment of contrast agent uptake in dynamic contrast-enhanced MRI

In previous papers relative signal intensity increase was used as a quantitative assessment parameter for contrast uptake in contrastenhanced MRI. However, relative signal intensity increase does not only reflect contrast uptake but depends also on tissue parameters (native T₁ relaxation time) and sequence parameters (repetition time and flip angle); thus, the contrast uptake cannot be assessed accurately using relative signal intensity increase. Based on an analysis of the contrast behavior of spoiled gradient echo sequences, a method is described in this paper that overcomes the limitations of relative signal intensity increase measurement. A parameter, called “enhancement factor” (EF) is introduced that approximates differential T₁ relaxation rate. The enhancement factor scales linearly with contrast uptake and is independent of tissue and sequence parameters. The additional measurement time involved in determining the enhancement factor is less than 1 min and computation is straightforward. The practicality of the new method was confirmed by phantom measurements using T₁-weighted and proton density-weighted spoiled gradient echo sequences (FLASH-2D). Enhancing tissues were simulated by water phantoms doped with increasing concentrations of Gd-DTPA.     

Behandlung des hypoplastischen Linksherz-Syndroms

In contrast to other types of congenital heart defects, the treatment of hypoplastic left heart syndrome (HLHS) has become comparably successful only within the last decade. Postnatal management of circulatory disturbances of HLHS was previously often performed, similarly to other types of neonatal shock, without considering the peculiarities of postnatal hemodynamics. It is of overwhelming importance to limit pulmonary hyperperfusion by reducing systemic afterload and avoiding artificial respiration. The invention of selective hypothermic cerebral perfusion using the modified Blalock-Taussig shunt has decreased the need for long circulatory arrest times involving the brain, and promises a better neurological outcome. Postoperatively, sophisticated hemodynamic monitoring is mandatory to provide sufficient systemic oxygen delivery. α-blockers are usually given for strong afterload reduction. Hospital mortality is as low as 10–15% in centers experienced with the Norwood operation. The next surgical steps to create a serial systemic and pulmonary circulation involve superior cavopulmonary anastomosis performed as early as possible (4–6 months) and finally total cavopulmonary connection at an age of 3–4 years.     

Sudden death in young soldiers. High incidence of syncope prior to death

During the years 1974 to 1986, 44 young soldiers (mean age 21 +/- 3 years) died suddenly and unexpectedly in the Israel Defense Forces. Cardiac causes accounted for 54 percent of deaths; neurologic causes, 14 percent of deaths; other diseases, 9 percent; and in 23 percent, cause of death was unknown. Although most sudden deaths are considered unpredictable, preceding symptoms were reported in more than one half of the patients. We found that syncope had occurred in 23 percent of cases, chest pain in 11 percent, and febrile disease in 16 percent. Exercise-associated syncope occurred in 16 percent and exercise-associated death occurred in most (86 percent) of those cases. Diagnosis at the time of the preceding symptoms failed to predict the fatal diseases in most cases. Our report points out the high incidence of syncope prior death in young soldiers with sudden death. Although further prospective controlled studies are needed in order to confirm that impression, we suggest that the possibility of syncope followed by sudden death should be kept in mind while evaluating young patients presenting with exercise-associated syncope.     

Cerebral hemodynamic and metabolic profiles in fulminant hepatic failure: relationship to outcome.

The purpose of this retrospective study was to examine the potential role of cerebral hemodynamic and metabolic factors in the outcome of patients with fulminant hepatic failure (FHF). Based on the literature, a hypothetical model was proposed in which physiologic changes progress sequentially in five phases, as defined by intracranial pressure (ICP) and cerebral blood flow (CBF) measurements. Seventy-six cerebral physiologic profiles were obtained in 26 patients (2 to 5 studies each) within 6 days of FHF diagnosis. ICP was continuously measured by an extradural fiber optic monitor. Global CBF estimates were obtained by xenon clearance techniques. Jugular venous and peripheral artery catheters permitted calculation of cerebral arteriovenous oxygen differences (AVDO2), from which cerebral metabolic rate for oxygen (CMRO2) was derived. A depressed CMRO2 was found in all patients. There was no evidence of cerebral ischemia as indicated by elevated AVDO2s. Instead, over 65% of the patients revealed cerebral hyperemia. Eight of the 26 patients underwent orthotopic liver transplantation-all recovered neurologically, including 6 with elevated ICPs. Of the 18 patients receiving medical treatment only, all 7 with increased ICP died in contrast to 9 survivors whose ICP remained normal (P < 0.004). Hyperemia, per se, was not related to outcome, although it occurred more frequently at the time of ICP elevations. Six patients were studied during brain death. All 6 revealed malignant intracranial hypertension, preceded by hyperemia. In conclusion, the above findings are consistent with the hypothetical model proposed. Prospective longitudinal studies are recommended to determine the precise evolution of the pathophysiologic changes.     

Mortality in elderly patients with thermoregulatory failure

Fifty-four elderly patients with thermoregulatory failure were evaluated retrospectively. The most commonly associated cause was underlying sepsis, which occurred in 78% of cases. Underlying conditions that increased the incidence of hypothermia were hypoproteinemia (50%), cachexia (30%), and neuroleptic medications (21%), most commonly thioridazine. Digoxin toxicity was a common finding (20% of all cases). One third of the patients developed hypothermia in warm months and half of them developed it while in the hospital. Patients who presented with hypothermia from out of the hospital had lower temperatures, were more bradycardic and hemoconcentrated, and died more rapidly than the in-hospital group. This could be explained by lower outside temperature or delay in diagnosis and treatment of the underlying disease. The overall mortality rate was extremely high (74%) in both groups. The mortality rate was not affected by age, sex, or degree of hypothermia. We conclude that thermo-regulatory failure in the elderly can occur in warm as well as cold environments or climates. The development of hypothermia in elderly patients should be promptly treated as sepsis unless proven otherwise, in light of the poor prognosis of this condition.