Ecological speciation in sympatric palms: 2. Pre- and post-zygotic isolation.

We evaluated reproductive isolation in two species of palms (Howea) that have evolved sympatrically on Lord Howe Island (LHI, Australia). We estimated the strength of some pre- and post-zygotic mechanisms in maintaining current species boundaries. We found that flowering time displacement between species is consistent across in and ex situ common gardens and is thus partly genetically determined. On LHI, pre-zygotic isolation due solely to flowering displacement was 97% for Howea belmoreana and 80% for H. forsteriana; this asymmetry results from H. forsteriana flowering earlier than H. belmoreana and being protandrous. As expected, only a few hybrids (here confirmed by genotyping) at both juvenile and adult stages could be detected in two sites on LHI, in which the two species grow intermingled (the Far Flats) or adjacently (Transit Hill). Yet, the distribution of hybrids was different between sites. At Transit Hill, we found no hybrid adult trees, but 13.5% of younger palms examined there were of late hybrid classes. In contrast, we found four hybrid adult trees, mostly of late hybrid classes, and only one juvenile F1 hybrid in the Far Flats. This pattern indicates that selection acts against hybrids between the juvenile and adult stages. An in situ reciprocal seed transplant between volcanic and calcareous soils also shows that early fitness components (up to 36 months) were affected by species and soil. These results are indicative of divergent selection in reproductive isolation, although it does not solely explain the current distribution of the two species on LHI.

Recent trauma is associated with antiretroviral failure and HIV transmission risk behavior among HIV-positive women and female-identified transgenders.

Trauma and posttraumatic stress disorder disproportionally affect HIV-positive women. Studies increasingly demonstrate that both conditions may predict poor HIV-related health outcomes and transmission-risk behaviors. This study analyzed data from a prevention-with-positives program to understand if socio-economic, behavioral, and health-related factors are associated with antiretroviral failure and HIV transmission-risk behaviors among 113 HIV-positive biological and transgender women. An affirmative answer to a simple screening question for recent trauma was significantly associated with both outcomes. Compared to participants without recent trauma, participants reporting recent trauma had over four-times the odds of antiretroviral failure (AOR 4.3; 95% CI 1.1-16.6; p = 0.04), and over three-times the odds of reporting sex with an HIV-negative or unknown serostatus partner (AOR 3.9; 95% CI 1.3-11.9; p = 0.02) and <100% condom use with these partners (AOR 4.5; 95% CI 1.5-13.3; p = 0.007). Screening for recent trauma in HIV-positive biological and transgender women identifies patients at high risk for poor health outcomes and HIV transmission-risk behavior.

Psychological trauma and PTSD in HIV-positive women: a meta-analysis.

Women bear an increasing burden of the HIV epidemic and face high rates of morbidity and mortality. Trauma has been increasingly associated with the high prevalence and poor outcomes of HIV in this population. This meta-analysis estimates rates of psychological trauma and posttraumatic stress disorder (PTSD) in HIV-positive women from the United States. We reviewed 9,552 articles, of which 29 met our inclusion criteria, resulting in a sample of 5,930 individuals. The findings demonstrate highly disproportionate rates of trauma exposure and recent PTSD in HIV-positive women compared to the general population of women. For example, the estimated rate of recent PTSD among HIV-positive women is 30.0% (95% CI 18.8-42.7%), which is over five-times the rate of recent PTSD reported in a national sample of women. The estimated rate of intimate partner violence is 55.3% (95% CI 36.1-73.8%), which is more than twice the national rate. Studies of trauma-prevention and trauma-recovery interventions in this population are greatly needed.

Fracture stabilization of proximal tibial fractures with the proximal tibial LISS: early experience in Birmingham, Alabama (USA).

This study is a prospective evaluation of the Less Invasive Stabilization System (LTSS) for the treatment of high-energy tibial plateau and proximal tibial fractures treated between November, 1998 and June, 2000. Thirty-two patients sustained thirty-five acute fractures of the tibial plateau (25) or proximal tibia (10). These patients were injured primarily in blunt trauma accidents, with eighteen having multiple fractures, fifteen having ipsilateral extremity fractures, and eleven having major knee ligament injuries. Seventeen patients had open fractures. Thirty-four patients healed their fractures, with one developing a nonunion. Two patients developed infections, both following Type III open fractures. Final range of motion averaged 2 to 116 degrees. Alignment was well maintained, with no patient losing the alignment that was obtained in the operating room. The tibial LISS system worked well at stabilizing difficult fractures of the tibial plateau and proximal tibia with a low incidence of complications in this preliminary study with short-term follow-up.

Are you paying too much for that acquisition?

Despite 30 years of evidence demonstrating that most acquisitions don't create value for the acquiring company, executives continue to make more deals, and bigger deals, every year. There are plenty of reasons why value isn't created, but many times it's simply because the acquiring company paid too much. It's not, however, that acquirers pay too high a price in an absolute sense. Rather, they pay more than the acquisition is worth to them. What is that optimum price? The authors present a systematic way to arrive at it, involving several distinct concepts of value. In today's market, the purchase price of an acquisition will nearly always be higher than the intrinsic value of the company--the price of its stock before any acquisition intentions are announced. The key is to determine how much of that difference is "synergy value"--the value that will result from improvements made when the companies are combined. This value will accrue to the acquirer's shareholders rather than to the target's shareholders. The more synergy value a particular acquisition can generate, the higher the maximum price an acquirer is justified in paying. Just as important as correctly calculating the synergy value is having the discipline to walk away from a deal when the numbers don't add up. If returns to shareholders from acquisitions are no better in the next ten years than they've been in the past 30, the authors warn, it will be because companies have failed to create systematic corporate governance processes that put their simple lessons into practice.

Comparison of synthetic saponin cholesterol absorption inhibitors in rabbits: evidence for a non-stoichiometric, intestinal mechanism of action.

The hypocholesterolemic activities of pamaqueside and tiqueside, two structurally similar saponins, were evaluated in cholesterol-fed rabbits. The pharmacological profiles of the saponins were virtually identical: both dose-dependently decreased the intestinal absorption of labeled cholesterol 25-75%, increased fecal neutral sterol excretion up to 2.5-fold, and decreased hepatic cholesterol content 10-55%. High doses of pamaqueside (>5 mg/kg) or tiqueside (>125 mg/kg) completely prevented hypercholesterolemia. Decreases in plasma and hepatic cholesterol levels were strongly correlated with increased neutral sterol excretion. Ratios of neutral sterol excreted to pamaqueside administered were greater than 1:1 at all doses, in opposition to the formation of a stoichiometric complex previously suggested for tiqueside and other saponins. Ratios in tiqueside-treated rabbits were less than unity, a reflection of its lower potency. Pamaqueside-treated rabbits exhibited a more rapid decline in plasma cholesterol concentrations than control animals fed a cholesterol-free diet, indicating that the compound also inhibited the absorption of biliary cholesterol. Intravenous administration of pamaqueside had no effect on plasma cholesterol levels despite plasma levels twice those observed in rabbits given pamaqueside orally. These data indicate that pamaqueside and tiqueside induce hypocholesterolemia by blocking lumenal cholesterol absorption via a mechanism that apparently differs from the stoichiometric complexation of cholesterol hypothesized for other saponins.

Kinetics of drug action in disease states. XLIII: Potentiating effect of L-tryptophan on the hypnotic action of phenobarbital and ethanol in rats.

The essential amino acid L-tryptophan has been widely used as a sleeping aid because it can produce drowsiness and decrease sleep latency. Its concentrations in plasma and brain and its binding to plasma protein are markedly altered in hepatic encephalopathy and renal failure. The purpose of this investigation was to determine if L-tryptophan can enhance the sensitivity of the central nervous system to the hypnotic actions of a barbiturate and an alcohol. Female rats weighing approximately 200 g received an intravenous infusion of L-tryptophan (0.8 or 0.08 mg/min) for 30 min and then an infusion of phenobarbital (0.824 mg/min) with L-tryptophan (0.8 or 0.08 mg min-1) until the onset of loss of righting reflex (LRR). Control animals received an infusion of saline solution for 30 min and then phenobarbital without the amino acid. Similar experiments were performed with ethanol (16.3 mg/min), with and without L-tryptophan (0.8 mg/min). L-Tryptophan infused alone at a rate of 3.8 mg/min for 84 min did not cause LRR. Administration of L-tryptophan at a rate of 0.8 mg/min with phenobarbital was associated with statistically significant reductions in the total dose and concentrations of phenobarbital in serum, serum water, brain, and cerebrospinal fluid (CSF) at onset of LRR. The 0.08 mg/min infusion of L-tryptophan had a less pronounced effect, with statistically significant reductions of phenobarbital concentrations at onset of LRR in brain and CSF. L-Tryptophan also significantly reduced the total dose and the concentrations of ethanol in serum, brain, and CSF required to produce LRR.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitation of the novel anticonvulsant remacemide in rat and dog plasma and urine: application of the plasma methodology to measure the plasma protein binding of remacemide.

Sensitive and selective methods have been developed for quantitation of the novel anticonvulsant remacemide in rat and dog plasma and urine. The methods employed liquid-liquid extraction (urine) or ion-exchange solid-phase extraction (plasma), with an internal standard, followed by high-performance liquid chromatography with ultraviolet detection. The detection limit for both methods was 10 ng/ml. Overall accuracy was 0.00% for plasma and -1.4% for urine with a precision of 6.04 and 3.87% for plasma and urine, respectively. The standard curves were linear for both plasma and urine over a wide concentration range (9.96-2490 ng/ml). The plasma method was also applied to measurement of in vitro plasma protein binding of remacemide in rat, dog and human plasma.

Biological profile of the metabolites and potential metabolites of the anticonvulsant remacemide.

Remacemide hydrochloride ((+/-)-2-amino-N-(1-methyl-1,2-diphenylethyl)- acetamide hydrochloride or FPL 1292AA) is a novel compound undergoing clinical trials for patients with generalized tonic/clonic and complex partial epilepsy. Remacemide exhibits efficacy against maximal electroconvulsive shock (MES) in rodents and seizures elicited by N-methyl-D,L-aspartate (NMDLA) in mice. Using rat synaptic membrane fractions, remacemide was shown to possess relatively weak noncompetitive binding to the ionic channel site of the NMDA (N-methyl-D-aspartic acid) receptor complex. With the hypothesis that activity against NMDLA-elicited seizures might be reflected by transformation to a more active metabolic species, the aim of the present study was to evaluate potential pharmacological effects of the 9 identified metabolites of remacemide which were all found in human and dog urine. Moreover, specific entities were recognized in plasma (including the rat's), as well as dog and rat cerebrospinal fluid. Five putative metabolites were also examined. A major route of metabolic transformation of remacemide in rats yields the formation of a pharmacologically active more potent desglycine derivative, namely FPL 12495 (+/-). Potency over the parent compound is revealed in the MES test in mice and rats, the NMDA-induced convulsions/mortality test in mice, and especially involving in vitro displacement of MK801 binding to the channel subsite of the NMDA receptor. The S isomer (FPL 12859) of this desglycinate is even more potent, while the R isomer is less potent than the corresponding racemate. Unlike the non-competitive NMDA antagonist, MK801, these desglycinates did not prevent kindled seizures. Three other identified metabolites show efficacy in the mouse and rat in vivo tests, namely the N-hydroxy-desglycinate (FPL 15053) and the p-hydroxy-desglycinates (FPL 14331 and FPL 14465). FPL 15053 exhibited modest activity in all tests. The only in vivo activity exhibited by the 2 p-hydroxy-desglycinates was evidenced in the MES test following i.p. and i.v. dosing. However, FPL 14331 was active in the MK801 binding assay. An oxoacetate metabolite, PFL 15455, failed to demonstrate any biological activity. Of potential metabolites tested 2 beta-hydroxy-desglycinates (FPL 14991 and FPL 14981) displayed modest activity in the MES test, however, only FPL 14981 prevented NMDLA-induced convulsions/mortality in mice and was 2-fold more active regarding MK801 binding. The hydroxy-methyl derivative of remacemide (FPL 13592) and its desglycinate (FPL 15112) prevented MES-induced convulsions only after i.v. administration; only the desglycine derivative displaced MK801 binding.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenocorticosteroid excretion in salt-sensitive and salt-resistant spontaneously hypertensive rats.

Two strains of spontaneously hypertensive rats (SHRs) differ in their susceptibility to the hypertensive effects of dietary NaCl. One strain exhibits a significant elevation of blood pressure after dietary NaCl loading (SHR-S), whereas the other does not (SHR-R). Since differences in adrenocortical steroid production may contribute to NaCl sensitivity, we compared 19-nordeoxycorticosterone (DOC), 18-OH-DOC, aldosterone, and corticosterone excretion in 6-week-old male rats from the SHR-S (n = 24) and SHR-R (n = 24) strains. The rats were housed in metabolic cages (two rats per cage) and given either basal (1%) or high (8%) NaCl diet. Urinary steroids were analyzed using thin-layer chromatography and radioimmunoassay methods. The high NaCl diet elevated the urinary excretion of the four corticosteroids in both rat strains. 19-nor-DOC decreased with time in both the SHR-S and SHR-R strains, and was not different between strains on either diet. Aldosterone was increased in the SHR-S strain compared with the SHR-R strain on the low NaCl diet, but aldosterone was not different between the two strains on the high NaCl diet. Corticosterone and 18-OH-DOC did not differ between strains. These data confirm that 19-nor-DOC is higher in young prehypertensive SHRs and decreases with age. Aldosterone excretion is higher in the SHR-S strain compared with the SHR-R strain on the low NaCl diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Cerebral interferon entry in mice after osmotic alteration of blood-brain barrier.

Systemically administered interferon (IFN) is not readily detected in the central nervous system (CNS) due to the presence of the blood-brain barrier (BBB). A method of osmotic BBB alteration in a mouse model was established in this laboratory. IFN's entry into the normal and osmotically altered brain after its intracarotid injection was investigated. Significant IFN levels (100-1,000 units) in the brain can be achieved by this method. The highest IFN activity was found in the brain hemisphere ipsilateral to the injection site within 20 min to 1 h after injection. IFN activity in the brain was detectable up to 4 h. Animals injected in this manner with murine IFN-alpha/beta (MuIFN-alpha/beta) and observed for a 6-month time interval showed no signs of neurological dysfunctions and resumed their normal activities. The therapeutic value of this method will be tested in a murine model of malignant glioma.

A mouse model for the study of blood-brain barrier permeability.

This article describes a C57BL/6 mouse model for the investigation of blood-brain barrier (BBB) alteration. Osmotic modification of BBB was achieved by infusion of 1.6 M arabinose solution into the internal carotid artery with or without occlusion of the external carotid artery. BBB alteration was measured by infusing 2% Evans blue dye. Only 1.6 M arabinose-treated animals but not 0.9% NaCl controls displayed prominent ipsilateral staining of frontal and temporal lobes. Light blue staining occurred in animals sacrificed within 10 min after injection. Prominent staining occurred in animals sacrificed 1-6 hours later. Identically treated animals were maintained for up to 6 months without signs of systemic or neurological dysfunction. This model may permit study of the effects of biological response modifiers (BRMs) upon the central nervous system (CNS) in healthy and diseased mice.

Long-term results of the Chrisman-Snook operation for reconstruction of the lateral ligaments of the ankle.

The Chrisman-Snook procedure for instability of the lateral ankle ligaments, first described in 1969, reconstructs the anterior talofibular ligament and the calcaneofibular ligament using one-half of the peroneus brevis tendon, routed through tunnels in the fibula and calcaneus. In the present long-term evaluation of the results of this procedure, forty-eight of sixty ankles, in fifty-seven patients, were assessed after a mean follow-up of ten years (range, four to twenty-four years). The results were excellent in thirty-eight ankles, good in seven, fair in two, and poor in one. The two ankles with a fair result were improved but still had some persistent instability, while the ankle with a poor result (no improvement) was in a patient with generalized ligament laxity. All three patients with a fair or poor result had had a severe reinjury to the ankle. Based on the findings in this study, we concluded that this procedure will restore good long-term function in a high percentage of patients who are disabled by ankle instability due to unhealed or neglected tears of the lateral ligaments.

Thromboembolism after surgical treatment of hip fractures.

Seventy-five patients ages 40 to 95 (average, 78), 60 of whom were women and 15 men, were admitted with upper femoral fractures and participated in a study designed to evaluate the possible prophylactic effects of platelet-inhibiting drugs on the incidence of thromboembolism. Aspirin, 600 mg, b.i.d., or a combination of the above doses of aspirin and hydroxychloroquine, 300 mg, b.i.d., were used from the time of admission. The study was prospective, consecutive except for a few exclusions, double-blind and randomized. Standard surgical treatment was given by three orthopedists. Venography by the 11th day was the endpoint, although daily examinations and early impedance plethysmography were also used. Twenty-five patients received placebos, 24 aspirin alone and 26 aspirin and Plaquenil. In the control group, 15 of 25 (60%) developed thrombosis and two had nonfatal pulmonary emboli. With aspirin, six of 24 (25%) had thrombosis and one a fatal embolus. In the combination group seven of 26 (27%) developed thrombosis and there were no emboli. No significant difference existed between treatment groups, but there was significant difference between the control and treatment group at the 2% level by the Yates chi2 test. Treated women received significant protection against thromboses (p less than 0.02); 13 of 20 untreated women had deep thromboses versus 12 of 40 in the treated women. Aspirin prophylaxis is significantly useful in fractured hip patients. The combination of aspirin and Plaquenil offers no additional benefit and only leads to complications from hematomas.

A long-term prospective study of the Hauser and Roux-Goldthwait procedures for recurrent patellar dislocation.

In a prospective study extending from 1966 to 1974, the results of the Hauser procedure were compared with the Roux-Goldthwait procedure for the correction of recurrent dislocations of the patella. In 87 knees in 75 patients, repaired consecutively and in a random manner with one procedure or the other, 100% retrieval was achieved. The average follow-up period was 7.7 years. Significant complications, though not necessarily of long term, occurred in 24 of 47 knees receiving Hauser repairs as compared with 6 of 40 knees in the Roux-Goldthwait group. Satisfactory long-term results were obtained in 72% with the Hauser technique and 93% with the Roux-Goldthwait technique.

Prevention of venous thromboembolism by administration of hydroxychloroquine. A preliminary report.

A placebo or the antimalarial agent hydroxychloroquine (Plaquenil), which inhibits platelet adhesiveness, and, to a lesser extent, platelet aggregation, was given to 100 patients between forty and ninety-five years old (average age, seventy-four years) who had either fractures or orthopaedic operations involving the skeleton between the knee and the pelvis. Medication was started at the time of admission in a blind, randomized way, fifty patients receiving hydroxychloroquine (200 milligrams three times a day) and fifty, a placebo. No untoward bleeding complications were noted in the treated group. Eight instances of thromboembolism were encountered in the control group as compared with one in the hydroxychloroquine-treated group, a statistically significant difference at the 1.5 per cent level.