Uterine evacuation with misoprostol during radiotherapy for cervical cancer in pregnancy.

Radiotherapy as definitive treatment for invasive cervical cancer during pregnancy causes spontaneous abortion in most cases. Surgical evacuation of the uterus is indicated when abortion does not occur, exposing patients to additional morbidity. Two Latin American women, diagnosed with FIGO stage IB2 cervical cancer at approximately 15 weeks gestation, underwent radiotherapy with radiosensitizing chemotherapy. After intrauterine fetal demise was detected, both women underwent induction with misoprostol. Results included one complete abortion and one incomplete abortion without complications or delays in treatment. These cases demonstrate that induction with misoprostol appears to be a safe and effective alternative to surgical evacuation of the uterus when spontaneous abortion fails to occur during radiotherapy for locally advanced cervical cancer.

Randomized clinical trial of soy formula with and without added fiber in antibiotic-induced diarrhea.

OBJECTIVE: The objective of this study was to examine the effects of soy formulas with and without added soy fiber in children who developed diarrhea while receiving antibiotics. DESIGN: In a masked, randomized parallel study, older infants and toddlers were fed commercial soy formulas with or without added soy fiber for 10 days on occurrence of diarrhea during the administration of antibiotics. Subjects were stratified by feeding (formula versus cow's milk). The primary variables were duration of diarrhea, stool characteristics, and intake. Secondary variables were weight and spit-up. RESULTS: All 45 children who completed the 10-day study received >30% of their caloric intake from formula. Fiber intake from other foods did not differ between groups and averaged 0.5 g/day. Total median fiber intake of the group fed the formula with added fiber was 6.53 g/day. The mean duration of diarrhea was 25.1 +/- 5.2 hours for children fed the formula with added fiber and 51.6 +/- 10.7 hours for those fed the regular formula (P =.0013). CONCLUSION: The duration of antibiotic-induced diarrhea in children fed the soy formula with added soy fiber was significantly reduced.

Influence of purine intake on uric acid excretion in infants fed soy infant formulas.

OBJECTIVE: These studies tested the hypothesis that increasing intake of purines, delivered as RNA from soy protein-based infant formula, would increase urinary uric acid excretion in infants. METHODS: Study One examined the influence of feeding on serum uric acid in a total of 178 infants from four separate trials with infants fed commercial and experimental soy-based and milk-based infant formulas or human milk. Studies Two and Three compared the effect of a standard purine soy formula (STD Purine; 180 mg purines/L from RNA) and a reduced purine soy formula (Reduced Purine; 65 mg purines/L; 26 mg/L from RNA and 39 mg/L from ribonucleotides) on urinary uric acid excretion in infants. In Study Two, 11 infants ranging in age from 16 to 128 days of age were fed both formulas in a random crossover design. Complete 72-hour urine collections were done at the end of each 11-day feeding period. Urinary uric acid excretion was expressed as mmol/day. In Study Three, 33 infants were enrolled before eight days of age and randomized to one of the formulas one week later. Spot urine samples were collected at 28 and/or 56 days of age and urinary uric acid concentration was expressed as mmol/mmol creatinine. RESULTS: In Study One, each of the feedings resulted in mean serum uric acid levels within normal reference ranges. Soy formula led to higher serum uric acid levels than human milk, and human milk to levels indistinguishable from cow milk-based formulas. In Study Two, infants excreted significantly more uric acid in the urine when fed the STD Purine formula compared to the Reduced Purine formula (0.86+/-.04 vs. 0.57+/-.04 mmol/d) (p = 0.006). In Study Three, infants fed the STD Purine formula had a significantly higher concentration of uric acid in their urine compared to those fed the Reduced Purine formula (2.1+/-0.2 vs. 1.4+/-0.1 mmol uric acid/mmol creatinine) (p = 0.0001). CONCLUSION: These data indicate that healthy infants can digest RNA and subsequently absorb the liberated purine ribonucleotides as determined by urinary uric acid concentration.

Growth of newborn, term infants fed soy formulas for 1 year.

Few studies have measured long-term growth in infants fed soy protein-based formulas. The effect of nucleotide (NT) supplementation of soy protein-based infant formulas on growth is unknown. Growth was therefore evaluated in healthy term infants fed a soy protein-based formula (SOY; n = 73), SOY with added NT (72 mg added NT/L) at human milk (HM) levels (SOYN, n = 73), or mixed feeding (MF, n = 67) in a randomized, masked, parallel 1-year feeding study. The MF group (a nonrandomized reference group) was fed HM exclusively from birth to 2 months of age followed by HM and/or a standard milk-based formula (Similac with Iron with no supplemental NTs) to 1 year of age. Results indicated that growth (weight, length, and head circumference) was normal and comparable among the three groups. All three groups had similar plasma albumin (at 2 months of age) and hemoglobin levels (at 12 months of age). Thus, this study demonstrated similar growth in the first year of life among infants fed MF feeding or soy formula with or without supplemental NTs.

Use of soy fiber in acute diarrhea in infants and toddlers.

Soy fiber has been shown to reduce the duration of watery stools during acute diarrhea caused by bacterial and viral pathogens in underdeveloped countries. A randomized blinded clinical trial was conducted with middle-class American children to assess the efficacy of soy fiber-supplemented infant formula. Stool characteristics, intake, and weight were recorded. Infants > 6 months of age (n = 44) fed soy fiber-supplemented formula (Isomil DF) had a significantly shorter estimated median duration of diarrhea (9.7 hours vs. 23.1 hours) than those fed soy formula (Isomil). The use of fiber-supplemented soy formula may reduce the duration of diarrheal symptoms in U.S. infants more than 6 months of age with acute diarrhea.

DNA damage enhances melanogenesis.

Although the ability of UV irradiation to induce pigmentation in vivo and in vitro is well documented, the intracellular signals that trigger this response are poorly understood. We have recently shown that increasing DNA repair after irradiation enhances UV-induced melanization. Moreover, addition of small DNA fragments, particularly thymine dinucleotides (pTpT), selected to mimic sequences excised during the repair of UV-induced DNA photoproducts, to unirradiated pigment cells in vitro or to guinea pig skin in vivo induces a pigment response indistinguishable from UV-induced tanning. Here we present further evidence that DNA damage and/or the repair of this damage increases melanization. (i) Treatment with the restriction enzyme Pvu II or the DNA-damaging chemical agents methyl methanesulfonate (MMS) or 4-nitroquinoline 1-oxide (4-NQO) produces a 4- to 10-fold increase in melanin content in Cloudman S91 murine melanoma cells and an up to 70% increase in normal human melanocytes, (ii) UV irradiation, MMS, and pTpT all upregulate the mRNA level for tyrosinase, the rate-limiting enzyme in melanin biosynthesis. (iii) Treatment with pTpT or MMS increases the response of S91 cells to melanocyte-stimulating hormone (MSH) and increases the binding of MSH to its cell surface receptor, as has been reported for UV irradiation. Together, these data suggest that UV-induced DNA damage and/or the repair of this damage is an important signal in the pigmentation response to UV irradiation. Because Pvu II acts exclusively on DNA and because MMS and 4-NQO, at the concentrations used, primarily interact with DNA, such a stimulus alone appears sufficient to induce melanogenesis. Of possible practical importance, the dinucleotide pTpT mimics most, if not all, of the effects of UV irradiation on pigmentation, tyrosinase mRNA regulation, and response to MSH without the requirement for antecedent DNA damage.

A role for interleukin-1 in epidermal differentiation: regulation by expression of functional versus decoy receptors.

Although human epidermis contains levels of interleukin-1 (IL-1) up to 100 times higher than other tissues, the role of this cytokine in epidermal biology is unknown. Here, we show that interleukin-1 regulates the expression of mRNAs for two proteins associated with the differentiated phenotype of human keratinocytes, cellular retinoic acid-binding protein type II (CRABP II) and small, proline rich protein 1 (SPRR1). The ability of IL-1 to induce these transcripts correlates directly with keratinocyte expression of the IL-1 receptor type I (IL-1 RI) during differentiation and inversely with the expression of the type II IL-1 receptor (IL-1 RII), shown in other cell types to be a nonfunctional, decoy receptor. Furthermore, addition to keratinocyte cultures of an IL-1 RI-blocking, but not an IL-1 RII-blocking, antibody reduces the levels of CRABP II and SPRR1 mRNAs in these cells. These data suggest that epidermal IL-1 functions to promote keratinocyte differentiation and that a change in the IL-1 receptor profile of these cells initiates this IL-1 response through a relative enhanced expression of functional IL-1 receptors.

Lipid inhibitors of platelet-activating factor (PAF) in normal human plasma.

Endogenous, human plasma-derived lipids that inhibit the platelet stimulating activity of platelet-activating factor (PAF) have been identified. Chromatographic fractionation of neutral lipid PAF inhibitors revealed a majority of PAF inhibitory activity comigrating with cholesterol and a second peak localized with free fatty acids. Plasma phospholipids demonstrated three distinct PAF inhibitory fractions in TLC regions corresponding to those of sphingomyelin, phosphatidylcholine and phosphatidylethanolamine. Three fractions (one neutral lipid and two phospholipid) specifically inhibited PAF-induced platelet activation. Thus, there are both specific and non-specific lipid inhibitors of PAF in normal human plasma. These plasma lipids may be important in the specific regulation of the diverse, potent biological activities of PAF in various physiological states.

Effect of dietary fiber (soy polysaccharide) on the severity, duration, and nutritional outcome of acute, watery diarrhea in children.

OBJECTIVE: To assess the effects of dietary fiber (soy polysaccharide) on the severity, duration, and nutritional outcome of acute, watery childhood diarrhea. METHODS: A total of 34 hospitalized Peruvian male infants between 2 and 24 months of age were randomly assigned to receive a soy-protein isolate, lactose-free formula with added soy polysaccharide (group SF, n = 19) or the same diet without added fiber (group S, n = 15). The consumption of formulas, stool amount and consistency, absorption of macronutrients, and change in anthropometric status were measured. RESULTS: Children in both groups were initially similar with regard to age, nutritional status, and prior duration and severity of diarrhea. Four patients in group SF (21%) and two in group S (13%) failed therapy because of recurrent dehydration or severe purging (P = .67). Formula intakes increased slightly during hospitalization (P = .03), but did not vary by dietary group (P = .73). Stool outputs declined significantly (P < .001) during hospitalization, but there were no significant differences by dietary group in either stool wet weight (P = .83) or dry weight (P = .87). Estimated median durations of liquid stool excretion after hospitalization were 43 hours in group SF and 163 hours in group S (P = .003). There were no significant differences in fractional or net absorption of macronutrients or change in anthropometric status by dietary group. CONCLUSIONS: Soy polysaccharide, while not affecting stool output, macronutrient absorption, or nutritional status during acute, watery childhood diarrhea, significantly and markedly reduced the duration of liquid stool excretion.

Prolactin concentrations in serum and milk of mothers with and without insulin-dependent diabetes mellitus.

Diabetes may affect the secretion of prolactin, the principal lactogenic hormone. Because adequate amounts are critical to the establishment of lactation, we assessed the prolactin status of 33 women with insulin-dependent diabetes mellitus (IDDM), 33 women without diabetes, and 11 reference women participating in a study of lactation from 2 to 84 d postpartum. Circulating concentrations of serum prolactin declined temporally for all women and did not differ significantly among any of the groups. During the first postnatal week, milk immunoreactive prolactin concentrations were lower for women with IDDM than for control and reference women and the inverse relationship between lactose and milk prolactin, which was significant at day 2 postpartum for reference women, was delayed until day 14 postpartum for women with IDDM. Early breast-feeding activity, increased breast-feeding frequency, and good glycemic control enhance prolactin secretion and should be promoted during lactation in women with IDDM.

Radiation-induced increased platelet-activating factor activity in mixed saliva.

BACKGROUND: Platelet-activating factor (PAF), a family of structurally-related phospholipid mediators of inflammation, is present in normal human mixed saliva; however, its role in oral biology and the homeostasis of oral host defense mechanisms remains to be established. EXPERIMENTAL DESIGN: The current study was designed to evaluate the salivary levels of PAF in patients with oral mucositis that developed as a complication of head and neck irradiation for oral cancer. PAF activity was assessed in platelet bioassay and expressed relative to the activity of authentic PAF, 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (C16:0-AGEPC). RESULTS: A significant increase in salivary PAF levels was observed in patients with mucositis (47,032 +/- 12,731 C16:0-AGEPC fmole equivalents/ml of saliva, mean +/- SE, N = 7) as compared with normal subjects (5,568 +/- 1,135 C16:0-AGEPC fmole equivalents/ml of saliva, N = 27). Phospholipid fractionation of the PAF isolated from the saliva of patients with mucositis by reverse phase high performance liquid chromatography revealed a single peak of activity that corresponded with the elution profile of C16:0-AGEPC, the most biologically active molecular species of PAF. In contrast, the PAF isolated from normal human mixed saliva contained multiple molecular species of PAF. CONCLUSIONS: These results suggest that this potent phospholipid inflammatory mediator may play a role in the inflammation and tissue injury associated with mucositis resulting from radiation treatment for oral cancer.

Acute endothelial cell contraction in vitro: a comparison with vascular smooth muscle cells and fibroblasts.

The contractile responses of cultured rat and calf endothelial cells (EC), vascular smooth muscle cells (VSMC), and fibroblasts (FB) to vasoactive mediators (thrombin, serotonin, bradykinin, and histamine), forskolin, and cytochalasin B were compared. Cells were grown on a pliable silicone membrane, and contraction was assessed, using time-lapse video microscopy, by recording changes in the wrinkling of the silicone as the cells exerted tension on the surface. We found that all cells contracted in the presence of serum or thrombin and that VSMC and FB also contracted with serotonin stimulation. Bradykinin and histamine were not contractants in this system. Discrepancies between these results and reports of changes in permeability of endothelial layers in vitro and in vivo may be due to (1) the vascular segment from which EC were studied or (2) the possibility that certain mediators may provoke a noncontractile response that results in gap formation. Thus changes in vascular permeability, which occur during inflammation, may have both contractile and noncontractile components. Forskolin, known to indirectly inhibit myosin light-chain kinase activity, and cytochalasin B were potent relaxants, suggesting a similar smooth muscle-like contractile mechanism for all three cell types.

A review of the hormone prolactin during lactation.

The principal lactogenic hormone, prolactin, secreted by the anterior pituitary is critical to the establishment of lactation, milk macronutrient content and milk production. The concentration of circulating prolactin increases during pregnancy so that by the end of gestation, levels are 10 to 20 times over normal amounts. However, prolactin is prevented from exerting its effect on milk secretion by elevated levels of progesterone. Following clearance of progesterone and estrogen at parturition, copious milk secretion begins. The minimal hormonal requirements for normal lactation to occur are prolactin, insulin and hydrocortisone. Prolactin stabilizes and promotes transcription of casein mRNA; may stimulate synthesis of alpha-lactalbumin, the regulatory protein of the lactose synthetase enzyme system; and increases lipoprotein lipase activity in the mammary gland. Prolactin levels decrease as lactation is established but nursing stimulates prolactin release from the pituitary which promotes continued milk production. Prolactin is secreted into milk at levels representative of the average circulating concentration. The physiological significance of milk prolactin to the infant is uncertain. Prolactin exists in three heterogenic forms which possess varying biological activity. The monomer with a molecular weight of 23 kDa is found in greatest quantity and is the principal biologically active form. The pattern of heterogeneity changes during pregnancy to favor even more monomer in proportion to the dimer. However, during lactation, the proportion of the monomer in circulation decreases in response to selective uptake of the monomer by the mammary gland. Over 90 percent of the prolactin in milk is present as the monomer. Prolactin may exert some of its biological effect by a shift in the ratio of active to less active forms of the molecule.

Quality-specific taste changes in multiple sclerosis.

Taste sensitivity in 79 patients with multiple sclerosis (MS) and 65 age- and sex-matched control subjects was measured with a sip-and-spit, suprathreshold scaling, magnitude estimation procedure using six concentrations each of sodium chloride, sucrose, citric acid, and quinine hydrochloride. Results were analyzed with a taste scoring system and by plotting psychophysical functions (log concentration versus log magnitude estimate) normalized to 1.0 M sucrose. Gender did not affect taste scores, but age was inversely related, so the results were analyzed by an analysis of covariance with age as the covariant. There was a significant alteration in taste sensitivity in the subjects with MS for sodium chloride and quinine hydrochloride stimuli but not for sucrose and citric acid; these results were confirmed by a separate analysis of the psychophysical functions. Some of the MS taste scores correlated with MS functional and physical disability scores. Taste sensitivity was not correlated with clinical history or presence of facial symptoms.

Zinc in multiple sclerosis.

Zinc profiles were examined in 68 patients with multiple sclerosis, 62 normal volunteers, and 13 patients with other neurological diseases. Plasma zinc levels were slightly increased in patients with multiple sclerosis and significantly increased in those with other neurological impairments (p less than 0.01), compared with control subjects. Albumin-bound as well as protein-bound zinc levels were normal in all groups tested. The alpha 2 macroglobulin-bound zinc level was significantly lower (p less than 0.01) in patients with multiple sclerosis than in control subjects. Erythrocyte-bound zinc levels were significantly increased (p less than 0.05) in patients with multiple sclerosis when compared with control subjects. Erythrocyte-bound zinc was normal in patients with other neurological impairments. Because erythrocyte-bound zinc levels are relatively independent of daily fluctuations in dietary zinc intake, an increase in these values may suggest alterations in the control mechanisms governing zinc compartmentalization in patients with multiple sclerosis.