CT scan the key to unmasking a solid pseudopapillary pancreatic neoplasm in blunt abdominal trauma.

SUMMARY: We present a previously healthy 13-year-old male, who sustained a handlebar injury after falling from his bicycle. The computerised tomography (CT) scan indicated a probable pancreatic neoplasm associated with a retroperitoneal haematoma which was, following resection, confirmed histologically to be a solid pseudopapillary neoplasm of the pancreas. These are rare tumours of the pancreas, especially in young males. The rarity of this neoplasm and the mechanism that led to its presentation make this an interesting and unique case.

Treatment of newly diagnosed diabetic cats with glargine insulin improves glycaemic control and results in higher probability of remission than protamine zinc and lente insulins.

Glycaemic control and remission probabilities were compared in 24 newly diagnosed diabetic cats treated twice daily with either glargine, protamine zinc (PZI) or lente insulin and fed a low carbohydrate diet. After day 17, the probability of remission was substantially higher for cats with lower mean 12h blood glucose concentrations on day 17, irrespective of insulin type. Glargine-treated cats had lower mean 12h blood glucose concentrations on day 17 than PZI- or lente-treated cats, and all eight glargine-treated cats achieved remission compared to three PZI- and two lente-treated cats. The probability of remission was greater for cats treated with glargine than cats treated with PZI or lente insulin. In newly diagnosed diabetic cats, twice daily treatment with glargine provides better glycaemic control and higher probability of remission compared to twice daily treatment with PZI or lente insulin. Good glycaemic control soon after diagnosis is associated with increased probability of remission and should be the goal of insulin therapy.

Glargine and protamine zinc insulin have a longer duration of action and result in lower mean daily glucose concentrations than lente insulin in healthy cats.

The pharmacological effects of glargine, protamine zinc (PZI), and lente insulins were evaluated in nine healthy cats. A 3-way crossover study was performed and plasma concentrations of insulin and glucose were determined for 24 h after a single subcutaneous injection of each insulin at 3-day intervals. Time to onset of action did not differ between insulins. Mean time to first nadir glucose was longer for glargine (14 h) relative to PZI (4 h) and lente (5 h). PZI was biphasic in action with nadirs at 4 and 14 h with the second nadir occurring at a similar time to glargine. Nadir glucose did not differ significantly between insulin types. The duration of action was similar for glargine and PZI and was longer than that for lente insulin. Mean daily glucose after glargine and PZI were also similar and were lower than after lente insulin. Time to reach peak insulin did not differ between insulin types. Time to return to baseline insulin level for PZI was longer than glargine but did not differ significantly from lente. In conclusion, healthy cats injected subcutaneously with glargine, compared to those injected with lente insulin, have a later glucose nadir and longer duration of action. Glargine and PZI had similar durations of action in study cats but a larger study is required to obtain precise comparisons of duration of action.

Enhancement of the activity of asparaginyl-tRNA synthetase by an activator from rabbit liver.

Asparaginyl-tRNA synthetase has been partially purified from acetone powders of rabbit liver. (NH-4)-2SO-4 fractionation was followed by chromatography of the enzyme on DEAE-cellulose. An activator separated from the enzyme. Further chromatography on Sephadex G-100 and G-200 showed that the latter consisted of two components. The smaller of these (mol wt is approximately equal to 35 000) possessed enzyme transfer activity but the larger one (mol wt 80 000-90 000) required the addition of activator before any enzyme transfer activity was demonstrable. The activator itself was devoid of transfer activity. After chromatography of crude extracts of asparaginyl-tRNA synthetase on Sepharose 4B the activity in the enzyme peak, which was of considerably larger molecular weight than any of the fractions found after purification could be enhanced by addition of the activator. None of the fractions of the enzyme or of activator catalysed any extensive asparagine-dependent ATP-PP-i exchange, either in the presence or the absence of added tRNA.

Review and critique of the new DSM-IV diagnosis of acute stress disorder.

OBJECTIVE: A new diagnosis can greatly influence scientific research, access to resources, and treatment selection in clinical practice. The authors review the historical evolution, rationale, empirical foundation, and clinical utility to date of the recently introduced diagnosis of acute stress disorder. METHOD: The conceptual basis and relevant methods for identifying a psychiatric syndrome are reviewed with respect to acute stress disorder, including selection of criteria for core symptoms; considerations of sensitivity and specificity of a syndrome definition; longitudinal course; and distinctions between normative and pathological phenomena. Particular attention is devoted to two major issues: the implications of the core feature requirement of three of five dissociative symptoms, and the question of whether there should be two separate diagnoses (acute stress disorder and post-traumatic stress disorder [PTSD]) describing posttraumatic syndromes. The widely divergent approaches in DSM-IV and ICD-10 are also reviewed. RESULTS: The diagnosis of acute stress disorder does not appear to achieve the important objective of providing adequate clinical coverage for individuals with acute posttraumatic symptoms. The validity and utility of requiring peritraumatic dissociative symptoms as a core feature are questionable, as is the separation of essentially continuous clinical phenomena into two disorders with different criteria sets (acute stress disorder and PTSD) based on persistence of symptoms for 30 or more days. CONCLUSIONS: Longitudinal studies using acute stress disorder criteria, as well as broader considerations of the clinical and scientific functions that posttraumatic diagnoses should serve, suggest a need to reevaluate the current DSM-IV approach to posttraumatic syndromes.

Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.

OBJECTIVE: This study evaluated the efficacy and safety of paroxetine for the treatment of patients with chronic posttraumatic stress disorder (PTSD). METHOD: Outpatients with chronic PTSD according to DSM-IV criteria and a score of 50 or more on the Clinician-Administered PTSD Scale, part 2, were randomly assigned to take placebo (N=186), 20 mg/day of paroxetine (N=183), or 40 mg/day of paroxetine (N=182) for 12 weeks. Efficacy was assessed by examining the change in total score from baseline to endpoint on the Clinician-Administered PTSD Scale, part 2, and rates of response ("very much improved" or "much improved") for global improvement on the Clinical Global Impression scale. RESULTS: Paroxetine-treated patients in both dose groups demonstrated significantly greater improvement on primary outcome measures compared to placebo-treated patients in the intent-to-treat analysis. Moreover, paroxetine treatment resulted in statistically significant improvement compared to placebo on all three PTSD symptom clusters (reexperiencing, avoidance/numbing, and hyperarousal), social and occupational impairment, and comorbid depression. Paroxetine was effective for both men and women. Treatment response did not vary by trauma type, time since trauma, or severity of baseline PTSD or depressive symptoms. Both doses were well tolerated. CONCLUSIONS: Doses of 20 and 40 mg/day of paroxetine are effective and well tolerated in the treatment of adults with chronic PTSD.

Comorbidity, impairment, and suicidality in subthreshold PTSD.

OBJECTIVE: Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD. METHOD: On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation. RESULTS: Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder. CONCLUSIONS: Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.

Childhood trauma and dissociative symptoms in panic disorder.

OBJECTIVE: Childhood trauma has been associated with increased risk for both panic disorder and dissociative symptoms in adulthood. The authors hypothesized that among individuals with a primary diagnosis of panic disorder, those experiencing depersonalization/derealization during panic attacks would be more likely to have a history of childhood trauma. METHOD: Rates of traumatic events were compared between panic disorder patients with (N=34) and without (N=40) prominent depersonalization/derealization during panic attacks. Symptom severity in the two groups was also examined. RESULTS: Contrary to the authors' hypothesis, no evidence was found that depersonalization/derealization during panic attacks was associated with childhood trauma. Minimal differences in severity of illness were found between patients with dissociative symptoms and those without such symptoms. CONCLUSIONS: This finding is consistent with a multifactorial model of dissociation. Factors other than childhood trauma and general psychopathology may underlie vulnerability to dissociative symptoms in panic disorder.

Attention-deficit hyperactivity disorder and comorbid psychosis: a review and two clinical presentations.

BACKGROUND: A review of literature relating attention-deficit hyperactivity disorder (ADHD) to adult-onset psychosis suggests that cases of comorbid ADHD and atypical neuroleptic-refractory psychosis may respond to psychostimulants. METHOD: Two patients are described who presented to the authors for clinical care. Data were gathered by reviewing hospital charts from previous admissions and by conducting serial mental status examinations over many weeks. Subjects chosen for presentation herein met DSM-III-R criteria for ADHD and atypical psychosis characterized by delusions or hallucinations. RESULTS: After each subject had suffered multiple neuroleptic-refractory psychotic episodes, both had been treated by adding psychostimulants to ongoing neuroleptic therapy. The patients were then observed by the authors to be free of psychosis for many weeks, both while taking neuroleptics and psychostimulants concurrently, as well as while taking only psychostimulants after neuroleptics had been withdrawn. CONCLUSION: When integrated with reports of five similar cases and a review of the literature, the above results suggest that further attention be given to the evaluation, treatment, and eventual classification of a potentially distinct patient group with ADHD and atypical psychotic episodes.

Medication therapy for social phobia.

Social phobia, though the third most common psychiatric disorder in the United States, has received little systematic attention until recently. Chronic and disabling symptoms usually precede other disorders in individuals with comorbidity, including alcohol abuse. Though about 80% of individuals do not seek treatment, controlled trials have demonstrated efficacy for several medications, of which phenelzine (an irreversible monoamine oxidase inhibitor [MAOI]) is the best studied. The benzodiazepines, clonazepam and alprazolam, also hold promise. New reversible MAOIs such as moclobemide and brofaromine are under investigation; fluoxetine and other serotonin selective reuptake inhibitors need further controlled study. The benefits of group cognitive-behavioral therapy also appear substantial. Issues for future investigation include long-term outcome, differential therapeutics, diagnostic subtyping, and combination treatments.

Ulnar artery as a coronary bypass graft.

BACKGROUND: The ulnar artery has been used as a coronary bypass graft in 8 patients when it was deemed unsafe to harvest the radial artery after evaluation of the arterial circulation in the forearm and hand. METHODS: The ulnar artery was removed from the lower three quarters of the forearm, along with its satellite veins. Dissection was commenced distally near the wrist and extended proximally to where the ulnar artery passed between the two heads of origin of the flexor digitorum superficialis. The artery was divided distally above the wrist joint and proximally at a point immediately below the origin of the common interosseus artery. RESULTS: Ten ulnar arteries were removed for use as coronary artery bypass grafts; two were rejected, one because of severe calcification and the other because of atherosclerotic occlusion. The remaining eight ulnar arteries were grafted successfully to coronary arteries other than the left anterior descending. No early hand or cardiac complications were observed. CONCLUSIONS: The ulnar artery is an alternative coronary artery bypass graft that may be used when the radial artery is dominant and cannot be removed without risk. The ulnar artery is in close proximity to the ulnar nerve and harvesting has the potential to injure the nerve. Therefore, until the use of the ulnar artery has been more fully evaluated it should be used only when other options have been exhausted.

Alternative psychotherapy approaches for social anxiety disorder.

Alternative therapies and therapy modalities for SAD are needed because: Established treatments (CBT and pharmacologic) do not help everyone who seeks help. Established treatments provide only partial decrease in symptoms for many patients. Patients may experience recurrence of symptoms in long-term follow-up. CBT does not reach enough patients in need. Alternative treatment approaches and modalities may also be needed to address the successful outcomes of CBT. Success in overcoming social anxiety symptoms can generate a whole new set of challenges. For example, a 31-year-old man who overcomes his fear of dating and begins his first romantic relationship may need a less symptomatically focused therapy to deal with issues that arise in this relationship. Likewise, a woman whose decreased social anxiety enables her to get a long-awaited promotion may need to deal with the stress of adjusting to her new responsibilities. An individual who overcomes phobia of public speaking and still has mild anxiety may need to graduate to a forum such as Toastmasters to provide continued exposure to further develop confidence and skills in public speaking.

Tamm-Horsfall glycoprotein in human amniotic fluid.

Radioimmunoassay of material cross-reacting with urinary Tamm-Horsfall glycoprotein in human amniotic fluid was carried out. The cross-reacting material was shown to be identical with urinary Tamm-Horsfall glycoprotein by double immunodiffusion and by crossed immunoelectrophoresis. The concentrations of the substance from 16-25 weeks pregnancy were found to increase from average levels of 0.9 mg . l(-1) to 4.9 mg . 1(-1) over this period. The concentrations were considerably higher (up to 33 mg . l(-1) close to term. Measurements of the glycoprotein in amniotic fluid may be a useful index for development of renal function in the foetus.

Phenylpropanolamine-induced psychosis. Potential predisposing factors.

Phenylpropanolamine (PPA) is a sympathomimetic drug contained in numerous over-the-counter and prescription decongestants and appetite suppressants. A range of adverse effects have been reported, including neuropsychiatric reactions in patients known to be taking recommended doses. Given that psychiatric symptoms are not included in the manufacturer's lists of adverse drug reactions, the incidence may be significantly higher. We report a cae of paranoid psychosis following use of a decongestant containing PPA and summarize the case report literature of psychiatric adverse effects to PPA in which doses were known and stated to be within recommended guidelines. A pattern of possible risk factors emerges from these reports. These may include 1) symptoms or history of mood spectrum disorder, 2) history of psychosis, 3) female sex, 4) family history of psychiatric disorder. The possibility that a higher incidence of adverse events occurs in a vulnerable population has not been systematically addressed, and seems called for. We recommend that physicians specifically inquire about patients' use of decongestants and diet aids. In half of the above cases, symptoms resolved without the use of antipsychotics.

Bupropion and sertraline combination treatment in refractory depression.

A sizeable minority of depressed patients, estimated at 15-20%, suffer chronic symptoms which often persist despite appropriate treatment. The search for new, more efficacious pharmacotherapies has included testing existing medications for additional therapeutic effects, such as in combination treatment. Four treatment- refractory patients who presented to the authors for clinical care are described, in which the combination of bupropion and sertraline was effective for a major depressive episode. None of the patients experienced adverse effects. Two carried the diagnosis of unipolar depression, and two, bipolar disorder. All had prior adequate, but ineffective, separate trials of buproprion and a selective serotonin re-uptake inhibitor (SSRI), including sertraline. All had chronic depression with multiple failed medication treatments, arguing against the alternative explanation that their improvement represented a placebo response or spontaneous remission. The efficacious combination of sertraline and bupropion may be due to synergism of its two distinct antidepressant mechanisms involving serotonergic, dopaminergic and noradrenergic systems.

Excretion of Tamm-Horsfall glycoprotein in renal disease.

Urinary Tamm-Horsfall glycoprotein (TH) excretion was measured by radioimmunoassay in 98 patients (55 men), aged 43.8 +/- 13.5 years, with renal disease. The radioimmunoassay was not affected by the urinary protein concentrations encountered. TH excretion (19 +/- 18 mg/24 h) was significantly lower than that in normals (39 +/- 13 mg/24 h; p less than 0.001) and was not related to age, sex or urine volume (1867 +/- 848 ml). TH excretion was not influenced directly by the degree of proteinuria (0.1-20.3 g/24 h), nor by variations in proteinuria with changes in disease activity or albumin infusions. There was a positive correlation between TH excretion and creatinine clearance less than 80 ml/min (r = 0.69, p less than 0.001). Patients with polycystic kidney disease had a disproportionate reduction in TH excretion with reduction in creatinine clearance. A major factor for the lessened excretion of TH in renal disease is probably a reduction in the number of functional distal tubular cells.

A study of immune responses to Tamm-Horsfall glycoprotein in the sera of patients with renal tubular acidosis.

Antibody to Tamm-Horsfall glycoprotein in the sera of patients with distal renal tubular acidosis (dRTA) was measured by radioimmunoassay, as well as in samples of normal human serum. Normal human serum contains small amounts of IgG capable of interacting with Tamm-Horsfall glycoprotein. Appropriate assays were carried out on antiserum raised in rabbits against human Tamm-Horsfall glycoprotein serially diluted with normal human serum. Corrections were applied for the presence of interfering substances in serum. The amounts of antibody found in samples of normal and patient sera were not significantly different, although some of the patients were diagnosed as having immune as opposed to familial dRTA. Studies of cell-mediated immunity to Tamm-Horsfall glycoprotein was found not to differentiate between the normal and patient samples. dRTA does not appear to be associated with immune responses to Tamm-Horsfall glycoprotein.

UDP-N-acetyl-D-glucosamine-asparagine sequon N-acetyl-beta-D-glucosaminyl-transferase-activity in human serum.

Serum contains a sugar transferase which is able to catalyse the glycosylation in vitro of the asparagine residue present in the sequence Asn.Leu.Thr in bovine pancreatic ribonuclease. UDP-2-Acetamido-2-deoxy-D-glucose (UDP-N-acetyl-D-glucosamine) acts as a donor, although the mechanism of the transfer is unexplored. Spermidine and Mn2+, as well as CDP-choline, can act as activators for the reaction. Monoglycosylated ribonuclease (ribonuclease-GlcNAc) has been separated (23% yield) from unreacted ribonuclease A by affinity chromatography on a column of wheat-germ agglutinin bound to Sepharose, and characterised. A possible reason for the presence of the enzyme in serum is suggested.

Structural analysis of the carbohydrate moieties of human Tamm-Horsfall glycoprotein.

Glycopeptides present in a pronase digest of human Tamm-Horsfall glycoprotein were fractionated by chromatography on DEAE-Sephadex A25 in 0.1M acetic acid. The separated glycopeptides were characterised by 500-MHz 1H-n.m.r. spectroscopy, in conjunction with sugar and amino acid analysis, and they were shown to be of the N-glycosylic, N-acetyllactosamine type. Each fraction consisted mainly of a tetra-antennary entity having various degrees of complexity, with lesser amounts of the triantennary structure, and even smaller amounts of the diantennary type. There was extensive heterogeneity in non-reducing terminal groups in each of the glycopeptides, whereas the peptide portions were similar. The extent to which any one of the galactose residues in the N-acetyllactosamine units was substituted, and the type of substitution, differed. The substituents were alpha-NeuAc-(2----6), alpha-NeuAc-(2----3), and alpha-NeuAc-(2----3)[beta-GalNAc-(1----4)]. The carbohydrate moieties of the glycoprotein were heterogeneous also because of an uneven distribution of the fucose residues, which were attached to GlcNAc residues, both that linked to asparagine and one or more of those present in the N-acetyllactosamine units. The alpha-NeuAc-(2----3)[beta-GalNAc-(1----4)]-beta-Gal-(1---- sequence forms, at least in part, the Sda immunodeterminant. The pKa of the carboxyl group of the sialic acid residue in this entity is lower than that for molecules lacking Gal-NAc in this position. Thus, the difference in the number of Sda determinants carried by the glycopeptides enabled the latter to be fractionated on DEAE-Sephadex.

Implications of recent findings in posttraumatic stress disorder and the role of pharmacotherapy.

Recent evidence suggests that an etiologic model of posttraumatic stress disorder (PTSD) must include both vulnerability factors (presumably related to dysregulation of stress responses and/or failure of normal restitutive mechanisms following trauma) and factors related to trauma severity. The fact that rates of PTSD increase with the severity of trauma suggests that normal adaptive mechanisms may become overwhelmed even in the absence of vulnerability factors. Consistent with this view, efforts to demarcate normative from disordered reactions to severe trauma, such as the new diagnosis of acute stress disorder, have had limited success. Debate over the moral and scientific implications of receiving a trauma-related diagnosis has further complicated the issue and perpetuated a false dichotomy concerning normative responses. The literature on clinical trials in PTSD is reviewed. The range of treatment responses, and the categorical breadth of compounds studied, requires interpretation before the literature as a whole can be understood. One of the many limitations of this new literature is the absence of treatment-outcomes research on individuals with the common comorbidity of substance abuse. The most recent findings with selective serotonin-reuptake inhibitors and related compounds indicate a more optimistic outlook for pharmacological treatment of PTSD than was suggested by earlier trials. Given these observations, investigators will hopefully be encouraged to pursue study and development of treatment models that include both pharmacological and psychosocial interventions.