Ethanol-induced hyperlacticacidemia: inhibition of lactate utilization.

The effects of oral ethanol administration on blood glucose and lactate concentrations, lactate inflow and outflow rates, and lactate incorporation into glucose were investigated in eight human volunteers. Lactate incorporation into glucose, lactate turnover, and lactate inflow and outflow rates were determined during an 8 hr constant infusion of 100 muCi of lactate-U-(14)C. Ethanol was administered by mouth at hourly intervals, 60 ml of bonded whiskey initially and 30 ml/hr thereafter. Blood lactate concentrations increased precipitously after the administration of ethanol, reached a plateau within 120-180 min, and remained constant thereafter despite the continued administration of ethanol. Before ethanol, the lactate turnover rate was 0.76 mmoles/kg per hr +/-0.05 (SEM) and lactate inflow and outflow rates were closely balanced. During the administration of ethanol, the lactate inflow rate was unchanged, but the lactate outflow rate was significantly inhibited, decreasing to 50% of the inflow rate. Despite the continued administration of ethanol, equilibrium between lactate inflow and outflow was restored within 120-180 min and coincided temporally with establishment of a constant blood lactate concentration. Lactate oxidation was unaltered by ethanol, but lactate incorporation into glucose was significantly inhibited. Lactate incorporation into glucose was reduced within 30 min of the administration of ethanol, and nadir values were reached within 120-180 min. Lactate incorporation into glucose remained constant thereafter at rates that were only 30% of those observed in the absence of ethanol. The results of these studies indicate that ethanol-induced hyperlacticacidemia is due to decreased lactate disposal rather than increased lactate production.

Glucose-lactate interrelationships: effect of ethanol.

The effect of ethanol on the interrelationship of lactate and glucose metabolism was investigated in eight human volunteers. Lactate and glucose kinetics and intervconversion rates were determined by the sequential administration of L-(+) lactate-U-(14)C and glucose-1-(14)C over an 8 hr period. After a 12 hr fast, the glucose turnover and recycling rates were 94.0 +/-3.8 (SEM) and 13.7 +/-1.1 mg/kg per hr, respectively. Approximately 50% of the glucose turnover or 40.7 +/-2.1 mg/kg per hr was converted to lactate, accounting for 50% of the lactate turnover rate. Lactate turnover and lactate conversion to glucose were 81.8 +/-6.2 and 16.7 +/-1.1 mg/kg per hr, respectively. Approximately 20% of the glucose turnover was derived from lactate under these conditions. During the administration of ethanol, the blood lactate concentration doubled and the lactate turnover rate declined slightly. Lactate conversion to glucose was markedly inhibited, decreasing from 16 to 5 mg/kg per hr, and the per cent of the glucose turnover derived from lactate decreased from 18 to 6. Despite the marked inhibition of lactate conversion to glucose, neither the blood glucose concentration nor the glucose turnover rate changed. Both glucose recycling and glucose conversion to lactate were decreased, indicating that ethanol inhibited peripheral glucose utilization. There was no difference in the degree of inhibition of lactate incorporation into glucose produced by ethanol when nonfasted subjects were compared with two subjects who had fasted for 48-72 hr despite the presence of hypoglycemia in the latter. These results indicate that starvation is not a prerequisite for ethanol inhibition of gluconeogenesis from lactate in humans but is necessary for the development of hypoglycemia. Inhibition of lactate incorporation into glucose in nonfasted subjects is probably masked by a concomitant increase in glycogenolysis which prevents hypoglycemia. Ethanol decreases glucose conversion to lactate as well as lactate conversion to glucose, thus inhibiting the Cori cycle.

An attempt at prevention of obesity in infancy.

A study of The Prudent Diet in early infancy was undertaken in a test group of 80 infants as an attempt to prevent overweight in a private practice setting. This group was compared with another group of 50 infants born in 1964 who were fed the standard infant diet then in use. Although an incidence of 34.1% overweight was present in the comparison group as compared with 25% in the diet group at age 3 months, by age 3 years the comparison still showed a 25.5% prevalence of overweight as compared with the study group with a significantly lower incidence of only 1.28%. These results require confirmation from other investigators, as well as long-term follow-up observation of patients before one could consider recommending such a diet for widespread use.

AKR lymphoma malignancy variants differing at late phase of metastasis.

The biological behavior of two AKR lymphoma variants, the TAU-39 and TAU-38, of low (LM) and high (HM) malignancy, respectively, has previously been described. In the present study an attempt was made to determine the phase in the metastatic process in which these variants differ. Two types of findings suggest that the two variants differ in the late phase of the process; (a) no difference in the degree of invasiveness of the primary tumor to the surrounding tissues has been found between the two variants, both being highly invasive; (b) comparison of malignant behavior in the "spontaneous metastasis" versus the "experimental metastasis" tests showed a similar ranking of malignancy of the two variants.

Early diagnosis and management of Alzheimer's disease.

It is only recently that Alzheimer's disease has become recognized as a major public health concern. Not only those diagnosed with Alzheimer's disease are impacted by the disease; the emotional toll exacted on caregivers is enormous, and the financial costs incurred by the United States are staggering. Early diagnosis of Alzheimer's disease can prevent costly and inappropriate treatment and permits earlier treatment of symptoms. There have been several recent pharmacologic advances in the treatment of Alzheimer's disease, including the development of acetylcholinesterase inhibitors. For any intervention to prove successful, however, early and accurate diagnosis and effective disease management are crucial.

Delusions and behavioral disturbances in cognitively impaired elderly persons.

OBJECTIVE: To compare cognitive function and the prevalence of selected behavioral problems in delusional and non-delusional dementia patients. DESIGN: Retrospective medical record review. SETTING: An outpatient geriatric assessment center. PARTICIPANTS: 114 consecutive patients with dementia. MAIN OUTCOME MEASURES: Delusions as recorded in a consultation report. RESULTS: Delusions were described in 25.5% of patients. A variety of behavioral disturbances were more common in delusional than non-delusional patients, including agitation, angry or hostile outbursts, urinary incontinence, wandering or pacing, and insomnia. While cognitive function as measured by the MMSE was similar in delusional and non-delusional patients (18.9 +/- 3.8 and 19.2 +/- 5.9, respectively), there was a statistically borderline tendency for delusions to occur more often in patients in the mid-range of cognitive impairment (17 less than or equal to MMSE less than or equal to 23) compared with patients with greater or lesser degrees of cognitive impairment (32% vs 17% respectively). CONCLUSION: Delusions in dementia are associated with a variety of behavioral problems. Further studies are needed to clarify the role of delusions in the development of disruptive behaviors in dementing illness.

Effect of preovulatory progesterone administration on the endometrial maturation and implantation rate after in vitro fertilization and embryo transfer.

Fifty-two women, who had 62 ovum aspiration cycles, received a progesterone (P) supplementation of 100 mg/day that was initiated 10 hours before human chorionic gonadotropin (hCG) administration and was continued over the following 6 days. Forty-eight women who had 74 ovum pick-ups, but did not get P, served as controls. Forty-four (84.6%) women of the treatment group, and 40 (83.3%) of the controls had ovum fertilization and embryo replacement. The fertilization and cleavage rates and the mean number of replaced embryos per embryo transfer (ET) cycle did not differ between the groups. Endometrial biopsies, from treatment group women with no fertilized eggs, which were taken 48 hours after ovum pick-up, mostly revealed an "advanced endometrial dating," in relation to the "day of hCG." Pregnancy rate per ET cycle for the treatment group was significantly higher than that of the controls; 41.2% versus 23.3%, respectively. It is concluded that the higher pregnancy rate resulted from an improvement in uterine receptivity.

Black thyroid adenoma. Clinical, histochemical, and ultrastructural features.

A 22-year-old woman with a "hot" thyroid nodule who was being treated with minocycline for severe acne vulgaris is presented. A partial thyroidectomy specimen revealed a black adenoma. Microscopically, the black pigment was found in the follicular cells and the colloid of the adenoma. The pigment was bleached with potassium permanganate and was Fontana-Masson stain positive. It was negative for iron, periodic acid-Schiff, and acid-fast Ziehl-Neelsen stains. All these feature suggest a melanin-like pigment. However, electron microscopic examination revealed a dense osmophilic material present within the lysosomes of the follicular cells. No melanosomes were present. Twenty-six previously reported cases are reviewed, and the possible mechanisms for the deposition of the pigment in the adenoma and its relation to minocycline degradation products are discussed.

Reversible anorexia and rapid weight loss associated with neuroleptic administration in Alzheimer's disease.

Weight loss and malnutrition despite adequate dietary intake has been reported to be part of the clinical course in advanced dementia of the Alzheimer type. We present a case of reversible weight loss associated with neuroleptic use in a patient with Alzheimer's disease and discuss a possible pathophysiological basis for the weight loss.

Leiomyoma of the urinary bladder.

Leiomyoma of the urinary bladder is a rarity but should be considered in the differential diagnosis of intramural neoplasm. We report a case illustrating clinical and pathological features in particular the immunohistochemistry. Etiology and differential diagnosis are discussed.

Bone marrow and peripheral blood modifications in C57BL mice administered with cyclophosphamide and levan.

The effects of cyclophosphamide (CY) and levan at low (0.1 mg) and high (10 mg) doses (previously found to inhibit and stimulate, respectively, B16 melanoma growth) were studied. in single and combined administration, on the blood and bone marrow of C57BL mice. Very marked changes in the cellular composition of blood and bone marrow were induced by the various treatments. CY caused a sharp depletion of leukocytes in blood and bone marrow followed by a restoration of granulocytes while lymphocytes remained low. Levan caused a sharp dose-dependent depletion in bone marrow lymphocytes. Blood lymphocytes were not affected, however, by the polysaccharide. With the high levan dose, after a temporary granulocytopenia and monocytopenia, prominent granulocytosis was observed. While CY affected equally the different types of cells, levan decreased the number of lymphocytes and erythroblasts to a greater degree than the number of granulocytes. In the combined CY-levan treatments, the low levan dose generally attenuated the suppressive effect of CY, while the high concentration aggravated it.

Cervico-isthmic pregnancy ending with the delivery of a live-born infant in late second trimester.

A very rare case of cervico-isthmic pregnancy, terminated by cesarean section in late second trimester with the delivery of a live-born infant who subsequently remained alive, is described. The authors suggest that this is the first case of neonatal survival in late second trimester of a cervico-isthmic pregnancy.

Macrophage-recognized molecules of apoptotic cells are expressed at higher levels in AKR lymphoma of aged as compared to young mice.

While a direct relation between aging and tumorigenesis is well established, a slower tumor progression rate was reported in old as compared to young cancer patients. The mechanisms responsible for the less aggressive behavior of tumors in the aged, are largely unknown. We have recently shown an increase in apoptotic cell death in tumors derived from aged as compared to young animals in the AKR lymphoma. This was shown by DNA flow cytometry and by the ladder type DNA fragmentation in agarose gel electrophoresis. Analysis of the expression of genes involved in apoptosis in tumors derived from young and old animals showed a lower bcl-2 expression in those from the aged. The Fas antigen, on the contrary, displayed higher expression levels on lymphoma cells derived from old than on those from young mice. Apoptotic cells are recognized and phagocytosed mainly by macrophages. One molecular property of apoptotic cells which is recognized by macrophages is a loss in cell surface sialic acid concomitantly uncovering galactose residues. While comparing the "eat me status" phenotype of the tumor cells derived from young and aged animals, by the use of lectins recognizing sialic acid and galactose residues, FACS analysis showed a decrease in cell surface sialic acid and a gain in galactose residues in aged as compared to young mice. Moreover, Western blot analysis showed that a 130 Kda sialylated membrane glycoprotein was expressed at a lower level in tumors from the old as compared to young mice. Our results, at both the cellular and molecular levels, particularly with regard to molecules recognized by macrophages, indicate that increased apoptotic cell death in tumors from old as compared to those from young animals constitutes, as we have previously suggested, one of the mechanisms of the age-related decrease in tumor progression rate.

Sensitivity to macrophages decreases with tumor progression in the AKR lymphoma.

Resistance to immune reactions, innate or acquired, may be one of the mechanisms responsible for the progression of tumors. We have, indeed shown higher numbers of macrophages surrounding low- as compared to high-malignancy cells. In the present study we examined the level of cell surface molecules known to determine sensitivity to macrophages, namely galactose (GAL) and sialic acid (SA) residues. A histochemical assay for identification of SA by electron microscopy showed a higher cell surface content on metastatic (MT) than on primary (PT) tumor cells. The FACS data seen with fluorescent lectins showed a higher binding of Sambucus nigra agglutinin, which identifies SA attached to terminal GAL in -2.6 or -2.3 linkage, in MT than in PT cells. Binding of Maakia amurensis lectin (MAL-1), which identifies SA at position 3 of GAL, showed that the MT cells contain two subpopulations, one binding more MAL-1 and another less. Cell sorting showed a more aggressive behavior of the first population. The comparison of Peanut agglutinin (PNA) binding, which identifies GAL, demonstrated a decreased amount of PNA receptors in MT as compared to PT cells. Western blot analysis of the membranal proteins with different lectins, identified 3 sialylated glycoproteins. The 88 kDa glycoprotein had no significance for metastatic potential. The 130 kDa glycoprotein was higher in MT than on PT cells. The 220 kDa glycoprotein was practically present only on MT cells. The tendency observed was of a higher level of membranal glycoconjugates terminally sialylated with subterminal galactose residues, inMT cells as compared to PT cells. This may explain the recently found decrease in apoptotic cell death with increasing aggressiveness of the AKR lymphoma and suggests a lower sensitivity to macrophages with tumor progression. Treatment based on the reduction in sialic acid content might render the tumor cells more vulnerable to macrophages. We found, indeed, that Wheat germ agglutinin (WGA) injected in vivo, exerted an inhibitory effect on growth of the lymphoma. We found moreover that WGA-treated tumor cells were more sensitive than nontreated cells to macrophages in vitro.

Freeze-preserved vein grafts and atherosclerosis. An experimental study.

Histopathological changes of three types of vein grafts were studied. Freeze-preserved, fresh human grafts and autografts were inserted as patches in the aorta of rabbits on regular and variable cholesterol diets. In all grafts the endothelium and adventitia were reconstituted after a few months. In the wall, smooth muscle and elastic tissue were markedly diminished and poorly oriented with accompanied collagenisation. Cholesterol diet led to progressive fat and/or calcium deposition with subintimal proliferation in the autografts and fresh xenografts. In contrast this was seen to a much lesser degree and later in freeze preserved xenografts, even on higher cholesterol diets. Deep freezing considerably reduces the cellularity of the graft and its metabolic ability to accumulate lipids. Freeze-preserved veins seem to be a suitable graft for vascular reconstructions in severely atherosclerotic patients and compare favorably with vein autografts.

The fate of the freeze-preserved xenograft: an experimental study on rabbits, cats, and dogs.

Freeze-preserved allografts have been used successfully in patients for vascular peripheral replacement, dialysis, and chemotherapy. Freezing of veins seems to decrease or abolish antigenicity by decreasing the viable cellular components of the grafts. To confirm its acceptance and consequently, the high patency rates of freeze-preserved vein grafts, we inserted segments of human veins preserved at -80 degrees Centigrade as arterial substitutes into rabbits, cats, and dogs and studied the morphological changes of these xenografts up to 2 years. In all the groups, the patency rate was satisfactory. In rabbits and dogs, the cellular inflammatory reaction around the grafts and suture lines disappeared after a few weeks; the endothelium was reconstructed at 2 months and a poorly differentiated cellular fibro-collagenous wall with prominent hyalin matrix was observed. In cats, however, the histio-lymphocytic infiltrate persisted in functioning grafts up to 2 years associated with adjacent prominent vascular and nerve proliferation. It is suggested that this inflammatory reaction has no deleterious effect on the graft; on the contrary, it promotes its neovascularisation and innervation. The cat proved to be a good animal model for vascular surgical experiments. Our study proved the poor antigenicity of freeze-preserved venous xenograft. It could, in the future, be used for human arterial substitutes.

Acute rupture of an ovarian pregnancy associated with a negative serum B-HCG.

A case of acute rupture of an ovarian pregnancy in which Beta Subunit of human chorionic gonadotropin was negative is presented. This is the first case known in the literature. Clinical and laboratory aspects of ovarian pregnancy are reviewed.

Phenotypic modulation of fibroblasts in massive ovarian edema: an immunohistochemical study of three cases.

An immunohistochemical study of three cases of massive ovarian edema revealed coexpression of vimentin, total actins, alpha-smooth muscle actin, desmin and low molecular weight cytokeratins in the stromal spindle cells composing the edematous ovarian tissue. In addition these stromal cells expressed smooth muscle myosin which is a marker for terminal smooth muscle differentiation. This remarkable fibroblastic cell plasticity in massive ovarian edema may represent yet another example of fibroblastic modulations occurring under the influence of microenvironmental stress factors.

[Colonic obstruction due to endometriosis and schistosomiasis].

A 40-year-old woman was hospitalized for mechanical colonic obstruction. The past history of ovarian endometriosis, and preoperative endoscopy and CT of the abdomen suggested the diagnosis of endometriosis. It was confirmed by pathological examination of the resected specimen, which also showed schistosomiasis. Repeated stool examination for the parasite ova were negative. Literature related to combined endometriosis and schistosomiasis as a possible etiology for mechanical colonic obstruction is reviewed.

Prognostic significance of p53 and ras p21 protein expression in surgically treated non-small cell lung carcinoma.

BACKGROUND AND OBJECTIVE: The prognosis of surgically treated non-small cell lung carcinoma (NSCLC) varies even after careful selection of the patients; the conventional grading and staging system is often deficient in determining which cases will profit best from surgery. Additional techniques are needed to permit better prognostic evaluation. METHODS: In this research, 2 markers of cellular proliferation, p53 and ras (p21) proteins were examined. The material used was from the same series reported previously which were immunostained with different cytokeratin markers for the same purpose. Immunohistochemical stainings of p53 and p21 were performed on the paraffin sections of 88 NSCLC specimens: 45 squamous cell, 22 adeno- and 21 large or undifferentiated carcinomas. RESULTS: At stage I, positive or negative stains of p53 and p21 provided no prognostic information since they had similar 5 year survival rates of approximatively 50% which is similar to the mean predicted survival rate for stage I. In this group as well, there was no significant difference in immunostaining, either in relation to the histological type or grade of the tumors. At stage III-IV, we found a trend, which, however, was not statistically significant, between positive immunostains of p53 and p21 proteins and longer survival. CONCLUSIONS: These results vary from our previous study on the expression of the differentiation marker cytokeratin 18, which showed that positive staining of tumor cells was associated with a statistically significant poorer prognosis at stage I regardless of histological types.