Relation between duration and severity in bereavement-related depression.

OBJECTIVE: Prolonged duration is commonly used as an indicator that bereavement-related depression (BRD) is pathological. DSM-IV replaced the traditional 1-year pathology cut-point by a 2-month cut-point. Yet, little evidence exists regarding the validity of these cut-points in indicating increased BRD severity. This study evaluated the validity of the 2-month and 1-year cut-points in differentiating less severe from more severe BRDs in a nationally representative U.S. sample. METHOD: National Comorbidity Survey respondents with BRD's (n = 152) lasting 0-8, 9-52 and >52 weeks were evaluated for depression severity using six severity indicators. Cut-point validity was established by discontinuities in severity levels between durations below and above the cut-point. RESULTS: Bereavement-related depressions of >52-week duration were significantly higher than 9- to 52-week BRDs on four of six severity indicators and on a cumulative overall severity measure of mean number of severity indicators per person, whereas ≤8-week and 9- to 52-week durational categories differed on one severity indicator and not on overall severity. Additional analyses using durations 0-12, 13-26, 27-52 and >52 weeks suggested that alternative <52-week cut-points also lack validity. CONCLUSION: The traditional 1-year cut-point validly identifies increasing BRD severity; DSM's 2-month cut-point does not. Duration does not indicate increasing BRD severity before 1 year. Research using the 2-month cut-point may yield misleading results.

Computed tomography findings of internal hernia after gastric bypass that may precede small bowel obstruction.

PURPOSE: This study evaluates computed tomography signs of internal hernia in gastric bypass patients, including several previously unreported signs suggestive of internal hernia. METHODS: Eighteen patients with surgically proven internal hernia were included in the study cohort. The signs analyzed included the mesenteric swirl, hurricane eye, mushroom sign, and dilated small bowel loops, as well as previously non-investigated signs such as bowel wall edema, engorged mesenteric vessels, engorged mesenteric lymph nodes, and hazy mesenteric fat. We also separately examined internal hernia patients without overt small bowel obstruction (SBO), since these are the patients most likely to get overlooked by radiologists. RESULTS: The most prevalent sign in all internal hernia patients was mesenteric vessel engorgement, seen in approximately 79-84 % of patients overall and 73-75 % of patients without overt SBO. The level of agreement between our two readers for the eight total signs reviewed was all moderate to substantial (using Cohen kappa values), reflecting their reliability as markers of internal hernia. The highest level of agreement was seen in vessel engorgement at 0.91, followed by three other signs [hurricane eye, SBO, bowel edema] with levels of agreement at 0.86. CONCLUSIONS: We conclude that more subtle signs of internal hernia should be included in radiologist search patterns for patients with internal hernia, especially those presenting multiple times for abdominal pain, as these may reflect surgically correctable intermittent herniations.

Impending aortic aneurysm rupture - a case report and review of the warning signs.

Abdominal aortic aneurysm (AAA) may present with subtle clinical findings. Recognition of the imaging features of an impending rupture is key for timely diagnosis. This report reviews the classic computed tomography findings of impending AAA rupture and presents a recent case which illustrates the key features.

Analysis of the DNA-binding affinity, sequence specificity and context dependence of the glucocorticoid receptor zinc finger region.

The glucocorticoid receptor binds with high affinity to glucocorticoid response elements (GREs), which commonly consist of imperfect DNA palindromes with hexameric core binding motifs separated by three base-pairs; the receptor dimerizes upon binding to these sequences, with one monomer occupying each core motif. To examine quantitatively the receptor-DNA interaction, and to characterize the effects of single base-pair mutations and sequence context on this interaction, we have studied the binding of a purified glucocorticoid receptor fragment, T7X556, to a 30 bp oligonucleotide containing a complex arrangement of potential receptor binding sites (RBS): two consensus core motifs, RBSo and RBSa reside in the same orientation and overlap by one base-pair, and a third site, RBSb, a partial match to the consensus separated by three base-pairs and in opposite orientation from RBSa. Using four different footprinting reagents, we detected a receptor dimer bound to one face of the DNA double helix, making close contacts with two adjacent major grooves. One monomer bound with high affinity to RBSa and the other bound with lower affinity to RBSb; transfection studies revealed that both binding sites were necessary for GRE activity in vivo. We measured the affinity of the receptor interaction with RBSa, RBSb and non-specific sites, and showed that protein binding at RBSb was improved approximately 150-fold by cooperativity with RBSa. Remarkably, T7X556 failed to bind to the consensus RBSo sequence, even when it was mutated to match exactly RBSa; the preference for RBSa over RBSo was due neither to the presence of RBSb, nor to occlusion of RBSo by protein bound at RBSa. To examine the relative contribution of each core nucleotide to the binding reaction, we saturated RBSo and RBSa with point mutations. The results implied that four RBSa nucleotides, (or 5'- x G x ACA-3'), may make specific contacts with the protein, as certain mutations at these positions reduced binding drastically. Consistent with the footprinting and transfection assays, equivalent mutations in RBSo had no effect on protein binding. Thus, these findings indicate that the consensus core motif alone is not sufficient to specify a functional RBS, and that flanking sequences create an appropriate context for protein binding.

The effect of a formula diet on preparation of the colon for barium enema examination. Impact on health care and costs.

A preliminary study of unselected ambulatory patients having barium enema examinations showed that 31.5% were optimally prepared for evaluation of polypoid mucosal lesions, but 29% had fecal material in the colon that could have obscured the lesions during examination. Although 38 of 42 patients took prescribed cathartics, 84% did not maintain a low-residue diet, as prescribed at this institution. Subsequently, 98 age-matched patients revealed detailed low-residue diet instructions or a formula diet before barium enema examination. Formula preparation resulted in 51% optimal and only 9.5% unacceptable studies compared with 25% optimal and 34% unacceptable examinations in the control group. Caloric intake averaged 700 kcal/day during low-residue diet preparation and was increased almost twofold with formula preparation; improvement was particularly noticeable in the elderly (556 vs 1,286 kcal/day). Prepackaged low-residue defined diets seem acceptable to patients when substituted for a low-residue diet. Bowel cleanliness is greatly enhanced before the barium enema examination, thus improving health care and reducing radiation exposure and costs.

Study of 60 patients with AIDS or AIDS-related complex requiring psychiatric hospitalization.

Sixty patients with acquired immune deficiency syndrome (AIDS) or AIDS-related complex were treated on a locked inpatient psychiatric unit over a 30-month period. The wide range of mental disorders exhibited by these patients, key aspects of patient management, and the difficulty in psychiatric differential diagnosis are described.

3,5-disubstituted 1,2,3,4-triazoles, 1 new class of xanthine oxidase inhibitor.

3,5-Bis(4-pyridyl)-1,2,4-triazole (PPT), 3-(4-pyrimidinyl)-5-(4-pyridyl)-1,2,4-triazole (PMPT), and 3-(4-pyridazinyl)-5-(4-pyridyl)-1,2,4-triazole (PZPT) are among the most active competitive inhibitors of xanthine oxidase among a series of 3,5-disubstituted triazoles synthesized for this purpose, inhibition constants being less than 1 times 10(-7) M for each. ED50 values in squirrel monkeys derived from first-order rate constants for the first and rate-limiting step of the sequence, xanthine leads to uric acid leads to allantoin plus CO2, range from 0.04 to 0.08 mg kg-1 orally, with unusually long durations of action attributable to asymmetric distribution of inhibitor within liver and gut as a consequence of enterohepatic recirculation. Sensitivity of rats, dogs, and anthropoid species to these, as to other xanthine oxidase inhibitors, is markedly less than that of the squirrel monkey, but the triazoles are at least an order of magnitude more active than the representative purine analogs tested.

Drug-induced modifications of the immune response. 12. 4,5-Dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids and derivatives as novel antiallergic agents.

The synthesis of a series of novel 4,5-dihydro-4-oxo-2-(substituted amino)-3-furancarboxylic acids, salts, esters, and amides is described. The title compounds when tested in the mediator-induced dermal vascular permeability and active anaphylaxis assays in rats demonstrated moderate to potent antiallergic activity. The [2-trans-(4-methylphenyl)cyclopropyl]amino analogue 53 emerged as the most active derivative. Thus, when administered intraperitoneally to rats at a dose of 100 mg/kg, it inhibited the action of the mediators serotonin, histamine, and bradykinin by 100%. In the active anaphylaxis assay in rats, compound 30 suppressed the edema by 81% at a dose of 100 mg/kg, following intraperitoneal administration.

2-(Aminomethyl)phenols, a new class of saluretic agents. 3. Effects of functional group reorientation and modification.

A series of modified 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to show that the diuretic responses, or lack thereof, may be obtained in a second species. Reorientation of the 2-(aminomethyl) group either meta or para to the hydroxyl substituent resulted in loss of diuretic effects. Similarly, replacement of either the phenolic hydroxyl or the aminomethyl group with other functional moieties substantially diminished saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 4. Effects of oxygen and/or nitrogen substitution.

A series of oxygen and/or nitrogen substituted 2-(aminomethyl)phenols was synthesized and tested orally in rats for saluretic and diuretic effects. Intravenous dog data are included as supplementary material to demonstrate diuretic responses, or lack thereof, in a second species. In general, substitution on nitrogen with groups other than lower alkyl or substitution on nitrogen and/or oxygen with groups resistant to hydrolysis substantially diminished or ablated saluretic effects.

2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution.

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.

Cytotoxicity and activation of CB1954 in a human tumour cell line.

CB1954 (5-aziridin-1-yl-2,4-dinitrobenzamide) is a monofunctional alkylating agent, to which Walker 256 cells are very sensitive. These cells express a nitroreductase which reduces CB1954 to a bifunctional crosslinking agent 5-(aziridin-1-yl)-4-hydroxylamino-2-nitrobenzamide. In vitro testing on the human colon line LS174T showed that the differential cytotoxicities between the monofunctional agent (CB1954), and the active species (generated in situ by the addition of NADH and the Walker rat nitroreductase) were smaller than anticipated due to the unexpected toxicity of CB1954 (IC50 value for CB1954 on LS174T cells of 78 microM). The toxicity of the chemically synthesised active form was less than if it had been generated in situ (on LS174T cells). Further experiments showed that NADH was toxic at the levels used to generate the active species (500 microM). Gel filtration and electrophoresis experiments demonstrated that the human colon carcinoma and choriocarcinoma cell lines MAWI and JAR, as well as LS174T express an enzyme of similar molecular weight to that of the 33 kD Walker cell nitroreductase, which is capable of reducing CB1954 to its toxic metabolite, and reducing MTT to its insoluble formazan salt. The expression of this enzyme presumably accounts for the unexpected toxicity of CB1954.

Dyspnea in dystonia. A functional evaluation.

BACKGROUND: Dystonia consists of action-triggered sustained focal muscle contractions, worsened by effort, and resulting in voice changes, abnormal posturing, and dyspnea. The cause of dyspnea, previously unexplained, is the basis of this report. METHODS: Since the maximal efforts required to perform pulmonary function testing (PFT) could worsen the muscular contractions in dystonic patients, we used several tests to identify possible causes of dyspnea. These included spirometry with flow volume loops (FVL), tidal volume breathing, maximum voluntary ventilation (MVV), and inspiratory and expiratory muscle pressures (PImax, PEmax), sitting and supine. We used cycle ergometry with arterial blood gas (ABG) values to detect cardiac/pulmonary limitations and respiratory inductive plethysmography (RIP) to assess chest wall/abdominal movements for synchrony. Dynamic videofluoroscopy (VF) assessed and recorded the action-triggered muscle activity of the upper airways and the diaphragm during quiet breathing, speech, swallowing, and maximal respiratory maneuvers similar to the efforts required during PFT. RESULTS: Twenty-six dystonic patients, 12 women and 14 men, ages 14 to 70 years (mean age, 52.3 years) were evaluated. Their neurologic classification included 22 primary (idiopathic) and 4 secondary (2 postneuroleptic use, 2 posstraumatic). Four patients originally classified as having focal dystonia had dyspnea and were found to have diaphragmatic and/or upper airway dysfunction too. The PFTs showed abnormal FVL and/or tidal volume breathing patterns, with intermittent interruptions of air flow during inspiration or expiration in 20 of 24 patients. The VF was abnormal in 24 of 26 patients: 19 patients had combined upper airway (UA) and diaphragmatic dysfunction (DD); 1 patient had UA dysfunction alone, and 4 patients had DD alone. Except for poor effort and/or dystonic movements, cycle ergometry was normal in 18 of 21 patients. The ABG values and/or pulse oximetry were normal in 19 of 22 patients. CONCLUSION: Dyspnea in dystonia appears to be due to excessive and/or dysynchronized contractions of the upper airways and/or diaphragm, with usually normal gas exchange. These spasmodic and irregular muscular contractions during speech and daily activities are associated with the sensation of excessive effort to overcome the spasms. Excessive spasms can be triggered during PFT and are best detected on FVL patterns coupled with dynamic VF.

Streptococcal endophthalmitis from contaminated donor corneas after keratoplasty. Clinical and laboratory investigations.

We report three cases of Streptococcus viridans endophthalmitis following penetrating keratoplasty in which S viridans was cultured from the recipient eye, McCarey-Kaufman (M-K) media, and corneoscleral rims. As a laboratory correlation, we investigated the ability of S viridans to survive in M-K medium supplemented with gentamicin. After M-K medium was inoculated with S viridans, it was stored overnight at 4 degrees C, after which the temperature was raised to 23 degrees C. Periodic colony counts were performed for up to 24 hours after warming. No killing occurred in the cold. Ten hours passed before there was one log reduction in the bacterial colony count. Organisms could still be cultured at 24 hours. We conclude that gentamicin alone may be inadequate prophlyaxis against S viridans contamination of donor corneas.

Streptococcus sanguis survival in K-Sol. Comparison of gentamicin and the fluoroquinolone antibiotics.

Viridans streptococci are poorly covered by gentamicin sulfate in corneal storage medium. To evaluate possible antibiotic alternatives among the newer broad-spectrum fluoroquinolone antibiotics, we compared the survival of the viridans representative Streptococcus sanguis in K-Sol with gentamicin sulfate (100 mg/L), norfloxacin (250 mg/L), ciprofloxacin lactate (250 mg/L), ofloxacin (250 mg/L), or no antibiotic. At 23 degrees C, K-Sol with gentamicin produced a 2-log kill by 80 minutes. By comparison, only one of the others (norfloxacin) had achieved a 2-log kill by 4 hours. At 4 degrees C, all antibiotics differed little from the control, and none was superior to gentamicin.

Topical nonsteroidal agents and corneal wound healing.

The effects on corneal wound healing of two topical nonsteroidal anti-inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti-inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found.

Liposome-entrapped PGE1 posttreatment decreases IL-1 alpha-induced neutrophil accumulation and lung leak in rats.

We found that treatment with liposome-entrapped prostaglandin E1 (Lip-PGE1), but not with empty liposomes and/or free PGE1, decreased the leak of intravascularly administered 125I-labeled albumin into lungs of rats given interleukin-1 alpha (IL-1 alpha) intratracheally. Lip-PGE1 treatment also decreased lung myeloperoxidase activity, lung lavage neutrophil increases, and lung histological abnormalities found in rats given IL-1 alpha intratracheally. Interestingly, decreased lung leak and lung neutrophil accumulation occurred when Lip-PGE1 was given intravenously 2.5 h after, but not immediately before, intratracheal IL-1 alpha administration. When Lip-PGE1 treatment was given both before and 2.5 h after IL-1 alpha administration, lung leak was decreased to baseline levels. Lip-PGE1 treatment given 2.5 h after IL-1 alpha administration also decreased lung oxidized glutathione levels, which increased in rats given IL-1 alpha intratracheally. We conclude that postinsult treatment with Lip-PGE1 decreases lung leak, neutrophil recruitment, and oxidative responses in lungs of rats given IL-1 alpha intratracheally.

Susceptibility of owl monkeys to Plasmodium falciparum in relation to hemoglobin and karyotype.

Humans with inherited abnormalities of hemoglobin (Hb) synthesis have less frequent and less severe infections of malaria. This study sought to determine if karyotypic variation in the owl monkey was expressed as differences in Hb moieties and if it offered a selective advantage in susceptibility to malaria. Five karyotypes of owl monkey were evaluated on the basis of the electrophoretic mobility of their major and minor Hb components. The results of 40 owl monkeys of different karyotypes demonstrated that statistically significant differences exist among karyotype I animals and those with karyotypes II, III, and V, particularly with regard to their HbA2 concentrations. This finding is of interest in light of the fact that karyotype I animals are considered to be less susceptible to infection with human strains of Plasmodium falciparum than karyotypes II, III, and V, which are viewed as being highly susceptible.

Pharmacokinetic evaluation of high-dose etoposide phosphate after a 2-hour infusion in patients with solid tumors.

Etoposide phosphate, a water soluble prodrug of etoposide, was evaluated at levels potentially useful in transplantation settings in patients with malignancies. For pharmacokinetic studies of etoposide phosphate in this phase I study, 21 patients with solid tumors were treated with etoposide phosphate given as etoposide equivalents of 250, 500, 750, 1000 and 1200 mg/m2 infused over 2 h on days 1 and 2, and G-CSF 5 micrograms/kg per day starting on day 3 until WBC was > or = 10,000/microliters. Qualitative, quantitative, and pharmacokinetic analysis was performed as reported previously. Rapid conversion of etoposide phosphate into etoposide by dephosphorylation occurred at all dosage levels without indication of saturation of phosphatases. Plasma levels (C(pmax)) and area under the curve (AUC) of etoposide phosphate and etoposide demonstrated linear dose effects. For etoposide, plasma disposition demonstrated biphasic clearance, with mean T1/2 alpha of 2.09 +/- 0.61 h, and T1/2 beta of 5.83 +/- 1.71 h. An AUC as high as 1768.50 micrograms.h/ml was observed at a dose of 1200 mg/m2. The total body clearance (TBC) showed an overall mean of 15.72 +/- 4.25 ml/min per m2, and mean volume of distribution (VDss) of 5.64 +/- 1.06 l/m2. The mean residual time (MRT) for etoposide was 6.24 +/- 1.61 h. In urine, etoposide but not etoposide phosphate, was identified with large quantitative variations (1.83% to 33.45% of injected etoposide equivalents). These results indicate that etoposide phosphate is converted into etoposide with the linear dose-related C(pmax) and AUCs necessary for use of this agent at the high dosage levels needed in transplantation protocols. A comparison of pharmacokinetic parameters of high-dose etoposide with the values observed in our study with etoposide phosphate revealed comparable values for the clinically important C(pmax) and AUCs, clearance, terminal T1/2 and MRT. In contrast to the use of etoposide, etoposide phosphate can be delivered in aqueous vehicles and therefore may offer the advantage of ease of administration.