Quantifying effectiveness and best practices for bumblebee identification from photographs.

Understanding pollinator networks requires species level data on pollinators. New photographic approaches to identification provide avenues to data collection that reduce impacts on declining bumblebee species, but limited research has addressed their accuracy. Using blind identification of 1418 photographed bees, of which 561 had paired specimens, we assessed identification and agreement across 20 bumblebee species netted in Montana, North Dakota, and South Dakota by people with minimal training. An expert identified 92.4% of bees from photographs, whereas 98.2% of bees were identified from specimens. Photograph identifiability decreased for bees that were wet or matted; bees without clear pictures of the abdomen, side of thorax, or top of thorax; bees photographed with a tablet, and for species with more color morphs. Across paired specimens, the identification matched for 95.1% of bees. When combined with a second opinion of specimens without matching identifications, data suggested a similar misidentification rate (2.7% for photographs and 2.5% specimens). We suggest approaches to maximize accuracy, including development of rulesets for collection of a subset of specimens based on difficulty of identification and to address cryptic variation, and focused training on identification that highlights detection of species of concern and species frequently confused in a study area.

Safety, tolerability, and pharmacokinetics of remacemide in children.

Eleven patients (nine males, two females), 9-14 years of age, received adjunctive therapy with remacemide in an open ascending-dose study at two residential centers in the United Kingdom. Children taking enzyme-inducing drugs were given remacemide twice daily, starting at approximately 4 mg/kg per day and doubling the dose at two weekly intervals to a target dose of approximately 16 mg/kg per day. Children not taking enzyme-inducing drugs (n = 5) received half of these doses. After the dose-escalation phase, remacemide was slowly withdrawn over 2 weeks except in two children who, because of apparent benefit, entered a continuation phase. Remacemide generally was well tolerated in doses up to 13.5 mg/kg per day. Adverse events were similar to those reported in adults, with central nervous system and gastrointestinal events being the most common. One patient died after a suspected seizure, which was unlikely to have been related to remacemide treatment. No adverse effects on neuropsychologic functioning were observed; effects on vital signs and laboratory variables were not clinically significant. The pharmacokinetic profile for remacemide and its desglycinyl metabolite in children is similar to that seen in adult patients. Plasma concentrations of remacemide and the desglycinyl metabolite are reduced in the presence of concomitant antiepileptic drugs with hepatic enzyme-inducing activity.

The effects on pupil size and accommodation of sympathetic and parasympatholytic agents.

The time-response effect of two currently used mydriatics, phenylephrine and tropicamide, were evaluated in 524 eyes. Four different types of dilating regimens were used: 2.5% phenylephrine, 10% phenylephrine, 0.5% tropicamide, and the combination of 2.5% phenylephrine and 0.5% tropicamide. The analysis indicated that the recovery from mydriasis occurs between 5.5 and 7.0 hours with 2.5% phenylephrine and at more than 7 hours with 10% phenylephrine. The 0.5% tropicamide induced rapid dilation, whereas the combined treatment, 2.5% phenylephrine plus 0.5% tropicamide, produced the largest maximum pupillary diameter. Tropicamide, alone or in combination, also produced a longer mydriatic effect, lasting more than 7.0 hours. The recovery from the cycloplegic effect of the mydriatics occurred between five and seven hours in the majority of patients, with tropicamide alone or in combination with phenylephrine requiring the most time to revert to normal ranges of accommodation. The findings in this study indicate that, in normal subjects, the recovery from the effect of mydriatic agents is longer than what is generally reported in the literature.

Lacrimal secretion stimulants: sigma receptors and drug implications.

3H-DTG (1.3-di(2-[5-3H]tolyl)guanidine) or 3H-haloperidol was added to sigma-receptors (25 nM) in the presence of 25 nM spiperone and incubated with increasing concentrations of bromhexine derivatives (phenylalkylamines; 10(-9) to 10(-2)M) in membrane homogenate suspensions. IC50 values for two derivatives ranged from 3.2 to 8.8 nM for both radioligands. A preferred derivative, 7A (N,N'-dimethyl-2-phenyl-ethylamine), yielded an IC50 of 7.8 nM for 3H-haloperidol but showed much less affinity in displacing 3H-DTG (IC50 = 900 nM). Applying the technic of Bromberg [Exp. Eye Res., 40:313-320, 1985], in vitro protein secretion rates were measured following stimulation of either lacrimal gland slices or isolated, intact lacrimocytes with the compounds. In vitro protein secretion rates exhibit a dose-response relationship with increases in protein release up to a concentration of 10(-8) to 10(-4) M for various derivatives of bromhexine and 10(-4) M for carbachol. By means of Schirmer strips, tear fluid was collected over a five minute period at 10 and 60 minutes post-dosing following the topical application (50 microliters) to the right eye of New Zealand white rabbits (n = 20-24) of 7A at various concentrations. Incubation of lacrimocytes with 7A alone (10(-4) M), with haloperidol (10(-4) M) alone or in combination show that 7A is acting as an agonist to stimulate protein release, whereas haloperidol is acting as an antagonist to inhibit release. In vivo protein secretion rates also show a dose-response curve (at both 10 and 60 minutes post-dosing) for 7A that reach a statistically significant maximum in the dosed eye at a concentration of 0.15% w/v. Analysis of protein extracts using size exclusion HPLC shows an increase in secretory proteins, particularly tear-specific prealbumin.

The presence of sigma-receptors in the lacrimal gland.

Applying the technic of S.A. Wolfe et al. [Endocrinology, 124, 1160-1172, 1989], we have established the presence of sigma receptors in isolated, but intact, lacrimocytes excised from main lacrimal gland tissue of the New Zealand white rabbit. 3H-Haloperidol was used as the ligand (0.5-2500 nM), in the presence of spiperone. From a Scatchard plot, a single binding site was statistically chosen over two sites for a majority of the data associated with the intact lacrimocytes. Kd (71.0 +/- 46.4 nM) and Bmax (588.2 +/- 166.7 fmol/mg of protein) values showed lower binding affinity but a similar density of sigma sites in rabbit lacrimocytes when compared to published results obtained for rat exocrine glands and brain tissue. Using the technic of McCann and Su [J. Pharm. Exp. Therap., 257, 547, 1991], membrane suspensions of the sigma receptor were also prepared and tested for binding to radioligands, 3H-DTG, as well as 3H-haloperidol. A Scatchard plot revealed two binding sites for 3H-DTG and one binding site for 3H-haloperidol. The high affinity site for 3H-DTG yielded a Kd of 1.04 +/- 0.64 nM, whereas, Bmax was 135.9 +/- 11.62 fmol/mg of protein. The low affinity site gave a Kd = 75.3 +/- 26.8 nM and Bmax = 344.0 +/- 222.0 fmol/mg of protein. The weaker site is suspected to be intracellular. IC50 values were determined for N,N-disubstituted arylphenylalkylamines (Kd approximately low nM).

Lonidamine in head and neck cancer: an overview.

Lonidamine (LNM) has been employed in the treatment of advanced head and neck cancer (H & N) primarily with radiotherapy. It has been proposed that LNM potentiates the effects of radiation by inhibiting repair of potentially lethal damage by interfering with the mitochondrial associated repair processes. In addition, LNM appears to be more effective with fractionated doses of radiotherapy, which in light of the current emphasis on hyper/accelerated fractionation schemes may make it more efficacious. Initial H & N studies comparing LNM treated patients to historical controls report a complete response (CR) rate of 65% versus 45% respectively. All major H & N sites were included. Subsequent nonrandomized Phase II studies, although containing small numbers of patients, showed LNM to be ineffective as a single agent in patients previously treated with chemotherapy and not significantly different when radiotherapy was given with conventional dose rates. In a randomized Phase III study in which patients received an accelerated radiotherapy schedule (150 cGy bid) with either lonidamine or placebo, the CR rate was not significantly different, however, the local regional control rate was 48% versus 25% in favor of the LNM group. In addition, the 3 and 5 year duration of resonse (44% and 42% versus 26% and 17%) was improved in the LNM group. However, the 3-year actuarial survival rate was not different (49% v 43%). In summary the role of LNM as a radiopotentiator in advanced head and neck cancer appears to improve the local control rate, although survival was not significantly changed. However, future studies employing hyperfractionation schemes may show that the improved local control rate will translate into improved survival.

The use of benzydamine HCl for the management of cancer therapy-induced mucositis: preliminary report of a multicentre study.

A multicentre study was undertaken to determine the effectiveness of benzydamine, a non-steroidal antiinflammatory drug, in relieving oral pain and inflammation due to cancer chemotherapy or chemoradiotherapy-induced mucositis. Benzydamine or placebo mouthwash was administered in a double-blind fashion to patients with established mucositis who complained of at least moderate mucositis pain. Preliminary review of the data reveals encouraging trends, subjects who received benzydamine consistently reporting more effective pain relief than those receiving placebo. Benzydamine mouthwash provided good to excellent relief of oral mucositis pain when rated by patients after one day (68% vs 47%) and by examiners both after one day (60% vs 40%) and overall (60% vs 42%). When only very good to excellent responses were considered, observer impressions of benzydamine's effectiveness were found to be statistically significant (p less than .04). These initial results are encouraging and, though not all results are statistically significant, appear to support the potential usefulness of benzydamine mouthwash in managing oral mucositis due to cancer therapy.

Review of the side-effect profile of buspirone.

In 984 patients with generalized anxiety disorder who received buspirone in double-blind studies, the incidence of drowsiness (9 percent) did not differ significantly from that (10 percent) reported in 334 patients who received placebo. A probability value of p less than or equal to 0.10 was the criterion for significance. The incidence of drowsiness in buspirone-treated patients was significantly less than that in each of the groups receiving diazepam (32 percent), clorazepate (26 percent), lorazepam (58 percent), or alprazolam (43 percent). The side effects that did occur significantly more frequently in the buspirone group than in the placebo group were dizziness (9 percent versus 2 percent), headache (7 percent versus 2 percent), nervousness (4 percent versus 1 percent), light-headedness (4 percent versus less than 1 percent), diarrhea (3 percent versus less than 1 percent), paresthesia (2 percent versus less than 1 percent), excitation (2 percent versus less than 1 percent), and sweating/clamminess (1 percent versus 0 percent). The severities of these effects were predominantly rated as only mild or moderate. Fatigue occurred less frequently in buspirone-treated patients than in those receiving any of the benzodiazepines, and weakness occurred more frequently in diazepam-treated patients. Depression occurred less frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or lorazepam. Impotence occurred only in clorazepate- and lorazepam-treated patients. Decreased libido occurred more frequently in diazepam-treated patients, whereas increased libido was more frequent in clorazepate-treated patients. Nausea was reported more frequently in buspirone-treated patients than in those receiving clorazepate, diazepam, or alprazolam; diarrhea occurred more frequently in the buspirone group than in the diazepam group. The mean daily doses of the various treatments were buspirone, 20 mg; diazepam, 20 mg; clorazepate, 24 mg; lorazepam, 3 mg; and alprazolam, 1.5 mg. In an open-field study in West Germany involving 5,414 patients, gastrointestinal-related complaints were the most frequently reported side effects.

Increased sensitivity of the elderly to the central depressant effects of diazepam.

The effects of diazepam on memory and psychomotor performance in healthy elderly (N = 12) and young (N = 12) individuals were examined. Diazepam was administered acutely in a single, oral 2.5 mg dose. Diazepam impaired memory, both immediate and delayed recall, and psychomotor performance in the elderly subjects. In addition, the drug caused an increase in self-reported sedation in elderly subjects but not in young subjects. These findings suggest an age-related increase in the sensitivity of elderly individuals to the central depressant effects of diazepam.

Adverse effects of single therapeutic doses of diazepam on performance in normal geriatric subjects: relationship to plasma concentrations.

Elderly normal volunteers (N = 12, mean age 70.4 years) were administered placebo or diazepam 2.5, 5, 10 mg in four consecutive sessions separated by at least a 1-week interval. Memory and psychomotor performance and plasma diazepam concentrations were assessed at baseline and at 1 and 3 h following drug administration. Significant impairments were found in response to all doses of diazepam. The maximum impairment occurred at 1 h, which coincided with the highest plasma concentration of the drug.

Buspirone: an anxioselective alternative for the management of anxiety disorders.

Buspirone HCl (Buspar) is a novel anxiolytic agent unrelated to the benzodiazepines or other psychotherapeutic agents. Animal studies support an anxioselective profile, i.e. relief of anxiety without sedation, muscle relaxation or anticonvulsant activity. Double-blind clinical studies show buspirone to be effective in the treatment of anxiety and anxiety in the presence of depression. The effects of buspirone on psychomotor function, physical dependence and abuse potential tests are similar to those seen with placebo treatments. Mechanism of action studies indicate activity in a variety of neuronal systems.

The side effect profile of buspirone in comparison to active controls and placebo.

Animal studies and the original study comparing buspirone with diazepam and placebo indicated that sedative-hypnotic side effects and impairment in psychomotor function would be less with buspirone than with diazepam. This was borne out by the present double-blind study in which almost 700 patients received buspirone. Mean daily doses were buspirone, 20 mg; diazepam, 20 mg; and clorazepate, 24 mg. Sedation, lethargy, and depression were significantly less with buspirone than with diazepam or clorazepate and were comparable to placebo. There was no indication that other types of side effects would differ significantly from those seen with the benzodiazepines. Nervousness, headache, and dizziness were experienced more frequently with buspirone than with placebo.

The effects of a "low-estrogen" oral contraceptive on carbohydrate metabolism during six months of treatment: a preliminary report of blood glucose and plasma insulin values.

A prospective study of carbohydrate metabolism was carried out on seven women by using an oral glucose tolerance stimulation test and measuring blood glucose and plasma insulin values over a 3-hour time period. The test was performed before and after 6 months of treatment with a "low-estrogen" oral contraceptive containing 0.4 mg of norethindrone and 35 micrograms of ethinylestradiol. There was no change in the weight or diastolic blood pressure of the women, but there was a slight elevation of the systolic blood pressure with treatment. There was no significant change in the plasma insulin values or in four of five blood glucose values. The 1-hour blood glucose value was significantly lower after 6 months of treatment. These results suggest that the "low-estrogen" oral contraceptives may reduce the secondary effects on carbohydrate metabolism seen with regular oral contraceptives.

An apparatus for indirect measurement of perceived distance.

Two methods of measuring perceived distance are contrasted. One of these, called a direct method, accepts the observer's direct response to perceived distance as a valid measure of the distance perceived. The other, called an indirect measure, uses the observer's direct response to a perception that is not perceived distance but which has a known relation to perceived distance in order to calculate the distance perceived. There are indications that the direct measure of perceived distance provided by the verbal report sometimes will be modified by cognitive factors. A procedure and apparatus for an indirect measure is suggested which is likely to be free of the cognitive effects found in verbal reports of distance. This apparatus adjusts the distance around which the line-of-sight to the object pivots as the head is moved laterally. The pivot distance at which no apparent motion of the object occurs with head motion is a measure of the perceived distance of the object.

Lipid and carbohydrate metabolic studies after one year of megestrol acetate treatment.

A prospective study of lipid and carbohydrate metabolic parameters was made in 22 women who had taken a daily oral dose of 0.5 mg of megestrol acetate for contraception for 1 year. Studies of the fasting blood cholesterol and triglyceride levels demonstrated no significant change. A 3-hour oral glucose tolerance test was performed before and after 1 year of treatment. After therapy, the fasting blood glucose levels were normal but the 0.5- and 2-hour levels were elevated. All but one of the plasma insulin levels were elevated at the 1-year test. Since body weights and the fasting levels of plasma growth hormone were unchanged, they were probably not involved in the carbohydrate alteration. These results point out the need for long-term studies and the necessity for investigating the metabolic effects of all progestogen contraceptives.

Carbohydrate and lipid studies during six months' treatment with megestrol acetate. Measurements of blood glucose, insulin, growth hormone, and triglycerides.

PIP: This paper reports a study of lipid and carbohydrate metabolism in 42 women who took megestrol acetate (MA) .5 mg daily for 6 months. Blood glucose, plasma insulin, fasting plasma growth hormone and fasting plasma triglycerides were measured both before and after 6 months of MA treatment. Before each test the women were instructed to eat a high carbohydrate diet for 3 days; they then reported in the morning after fasting overnight. After a blood sample was drawn, they were given a solution of 100 gm glucose to drink and blood samples were drawn at .5, 1,2, and 3 hours. Although the group mean weight increased 3.6 pounds, there were minimal changes in the glucose or insulin curves, with only the slight elevations at the 2 hour drug test being significant. There were no significant changes in the growth hormone or triglyceride values. The data suggest that the substituted-progesterone progestins in oral contraceptives exert little metabolic effect as compared to the 19-norprogesterone progestins. Thus MA might be used for contraceptive purposes without producing carbohydrate or lipid metabolic changes.^ieng

Pharmacophysiologic and clinical aspects of oral contraceptives.

PIP: To date, 2 synthetic estrogens and 8 progestogens have been incorporated in the marketed oral contraceptives (OCs) in the US. At present 21 pills are available representing 14 different estrogen and progestin combinations and 1 minidose progestogen (alone). 2 OCs utilizing substituted progesterone as the progestin component have been withdrawn from the market. All of the OCs now available in the US utilize substituted testosterone as progestins. The trend is toward prescribing low estrogen dose OCs perhaps resulting from the statistical relationship between higher estrogen dose OCs and thromboembolism.^ieng