Stalled cerebral capillary blood flow in mouse models of essential thrombocythemia and polycythemia vera revealed by in vivo two-photon imaging.

BACKGROUND: Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPNs) that share the JAK2(V617F) mutation in hematopoietic stem cells, leading to excessive production of predominantly platelets in ET, and predominantly red blood cells (RBCs) in PV. The major cause of morbidity and mortality in PV and ET is thrombosis, including cerebrovascular occlusive disease. OBJECTIVES: To identify the effect of excessive blood cells on cerebral microcirculation in ET and PV. METHODS: We used two-photon excited fluorescence microscopy to examine cerebral blood flow in transgenic mouse models that mimic MPNs. RESULTS AND CONCLUSIONS: We found that flow was 'stalled' in an elevated fraction of brain capillaries in ET (18%), PV (27%), mixed MPN (14%) and secondary (non-MPN) erythrocytosis (27%) mice, as compared with controls (3%). The fraction of capillaries with stalled flow increased when the hematocrit value exceeded 55% in PV mice, and the majority of stalled vessels contained only stationary RBCs. In contrast, the majority of stalls in ET mice were caused by platelet aggregates. Stalls had a median persistence time of 0.5 and 1 h in ET and PV mice, respectively. Our findings shed new light on potential mechanisms of neurological problems in patients with MPNs.

Micromachining bulk glass by use of femtosecond laser pulses with nanojoule energy.

Using tightly focused femtosecond laser pulses of just 5 nJ, we produce optical breakdown and structural change in bulk transparent materials and demonstrate micromachining of transparent materials by use of unamplified lasers. We present measurements of the threshold for structural change in Corning 0211 glass as well as a study of the morphology of the structures produced by single and multiple laser pulses. At a high repetition rate, multiple pulses produce a structural change dominated by cumulative heating of the material by successive laser pulses. Using this cumulative heating effect, we write single-mode optical waveguides inside bulk glass, using only a laser oscillator.

The use of primidone in the treatment of refractory bipolar disorder.

Four anticonvulsant medications (carbamazepine, valproate, gabapentin and lamotrigine) have received attention in the psychiatric literature as efficacious treatment for bipolar disorder, either as monotherapy or as adjunctive agents. Although two earlier reports in 1993 suggested that primidone may also be helpful for bipolar disorder, this older anticonvulsant has not been evaluated in any subsequent studies to confirm these earlier findings. In the present prospective open study, 26 patients with refractory bipolar disorder were treated with primidone as an adjunctive therapy. Eight (31%) patients experienced a persistent positive therapeutic effect. Five (19%) patients were considered partial or temporary responders to primidone. The remaining 13 patients (50%) were considered treatment failures. Although a 31% response rate is considered modest in most psychotropic medication studies, the authors believe that this success rate is significant in this refractory patient population and should provide impetus for future more scientific studies to confirm the preliminary findings of this open trial.

Open maintenance treatment of bipolar disorder spectrum patients who responded to gabapentin augmentation in the acute phase of treatment.

This report describes the results of maintenance treatment with gabapentin in 18 previously refractory Bipolar Disorder patients who initially responded to augmentation with gabapentin during the acute phase of their therapy. Seven of the original 18 patients (39%) have continued to experience benefit from maintenance gabapentin treatment. Only three patients had to discontinue the gabapentin because of side effects. None of the 18 patients experienced an obvious significant adverse drug-drug interaction. Five of the patients discontinued gabapentin because of diminished clinical efficacy after a significant period of positive therapeutic effect. The results of this small open study suggest that gabapentin may be effective as an augmenting agent in the maintenance phase of treatment of some bipolar spectrum patients.

Minimally disruptive laser-induced breakdown in water.

We produce minimally disruptive breakdown in water by using tightly focused 100-fs laser pulses and demonstrate the potential use of this technique in microsurgery of the eye. Using time-resolved imaging and piezoelectric pressure detection, we measure the magnitude and speed of propagation of the pressure wave produced in the breakdown. Compared with breakdown with longer pulses, here there is a much lower energy threshold for breakdown of 0.2microJ , a smaller shock zone diameter (11microm for 1-microJ pulses), and consistent energy deposition.

Are some symptoms of depression age dependent?

177 depressed patients were examined to see whether age was associated with the presence of specific symptoms or symptom clusters. 14 of the 39 tested variables were significantly associated with age. Patients age > or = 40 were more likely to have terminal insomnia, agitation, diurnal variation with lower mood in the morning and the RDC subtype diagnoses endogenous, incapacitated or agitated. Patients age < or = 39 were more likely to have hypersomnia, increased appetite, weight gain, decreased libido, headaches, diurnal variation with worsening of mood in the afternoon and a mood characterized as sad not anxious.

Evaluation of intraperitoneal and intrahepatic administration of a euthanasia agent in animal shelter cats.

One hundred eighty-one adult cats, with body weight greater than 1.8 kg, were obtained from animal shelters, then were administered a sodium pentobarbital-lidocaine euthanasia agent by either the intraperitoneal (IP; n = 77) or intrahepatic (IH; n = 85) route. A preliminary study (n = 19 cats) indicated that most cats gave no indication of perception of injection (responding) if restraint was minimal and injection was rapid. During IP injection, 3 of the 77 cats (4%) responded (turned the head backward or vocalized). Of the 85 cats given IH injection, 8 (9%) responded; however, no response approached the magnitude of that observed after IM injection of ketamine hydrochloride. After either injection route, cats were observed for excitement (any exaggerated activities of stage-I and -II anesthesia (eg, vocalizing, flopping, sneezing, licking, running, paddling), and after cardiac standstill, cats were necropsied to identify exact location (final site) of the injection. Of 53 initial IP injections, final site for 22 (42%) was in the peritoneal cavity (PC). Use of a sideport needle (n = 24) did not significantly increase accuracy of IP injection. The small and large intestines were penetrated by 27% (15/55) of the IP injections from the right side, and the spleen was penetrated by 32% (7/22) of the left-side injections. Intrahepatic injection was significantly (P less than 0.05) more accurate, with 70 of 85 (82%) of the final sites being the liver only, the liver/PC, or the PC only. Twenty-five percent (13/53) of IP injections resulted in excitement (all stage-I and -II anesthesia-exaggerated activities cumulative to 30 seconds).(ABSTRACT TRUNCATED AT 250 WORDS)

Mast cell tumor destruction by deionized water.

In a controlled study, malignant murine P815 mastocytoma cells exposed in vitro to distilled and deionized water died as a result of progressive swelling, degranulation, and membrane rupture. A 90% mean cell death occurred when cells obtained directly from culture were exposed to deionized water for 2 minutes. Of 6 cryopreserved malignant murine cell lines, which included Cloudman S91 melanoma, CMT-93 rectum carcinoma, MMT-06052 mammary carcinoma, and S-180 Sarcoma, only P815 mastocytoma and YAC-1 lymphoma were significantly (P less than 0.05) affected by hypotonic shock; Cloudman S91 melanoma cells were the most resistant. Mastocytoma cells were selectively killed by hypotonic solution, and lymphoma cells were also killed by isotonic saline solution. Local mast cell tumor (MCT) recurrence and percentage survival were evaluated in 12 cats (21 MCT) and 54 dogs (85 MCT) subjected to surgery alone or local infiltration of deionized water as an adjunct to surgery. Of all 16 incompletely excised MCT in cats, there was no local recurrence following injection. Four mast cell tumors (2 cats) regressed after being injected in situ. In dogs with clinical stage-I MCT, local recurrence was detected in 50% (5/10), but with injection after incomplete excision, local MCT recurrence was significantly (P less than 0.05) less (6.6%, 1/15). Percentage recurrence was significantly (P less than 0.05) less and survival significantly greater when incompletely excised grade-II MCT were injected. Mean follow-up period after surgery in cats and dogs was 35 and 23.4 months, respectively.

Antidepressant response in chronic major depression.

Treatment response to antidepressant medication was examined in 59 patients with nonchronic major depression and 35 patients with chronic major depression. Patients with chronic major depression had a poorer response to imipramine or desipramine than nonchronic patients.

Survey method for post-marketing drug surveillance: a demonstration.

Distinguishing characteristics of a community survey method for post-marketing drug monitoring are described, as are results of a pilot study of the method. Representative samples of outpatients treated with tricyclic antidepressants or benzodiazepine anxiolytics were identified in a clinic or pharmacy and interviewed at baseline and specified intervals thereafter in the home or by telephone. Data were collected by lay interviewers trained to use a detailed interview schedule designed with input from experts in pharmacology, relevant clinical disciplines, and survey research. The critical validity question was the degree to which predicted outcomes for the two well-studied drug classes matched observed outcomes. The analytic design involved two contrast groups, three measurement periods, and six key symptom measures. The latter were specific to the disorder (anxiety and depression), to the medications, or to neither the disorders nor the medication (neutral symptoms). Predictions took account of degree and direction of change, as well as differences in profile levels over time. Results conformed precisely to expectations. As one component of a comprehensive system, the method provides an opportunity to examine efficacy as well as safety under conditions that are typically absent or excluded in clinical trials. Data on patterns of prescribing by physicians and use by patients are valuable by-products that are immediately relevant for professional education and product liability. Advantages and limitations of the method are discussed.

Elevation of the renal enzyme N-acetyl-beta-glucosaminidase in affectively disordered patients.

A minority of patients with affective disorders experience mild elevations of the renal enzyme N-acetyl-beta-glucosaminidase (NAG). Some affectively disordered patients also have reduced concentrating ability and reduced creatinine clearance. Thirty-one affectively disordered patients were compared to 17 healthy controls, to evaluate whether these various renal abnormalities are associated with one another and to further examine the proportion of affectively disordered patients experiencing NAG elevations. Twenty-nine percent of patients had an elevated NAG, whereas none of the controls did (P less than .005). There was a trend for an association between elevated NAGs and reduced creatinine clearance (P less than .08), but no association was found between concentrating ability and either elevated NAG or reduced creatinine clearance.

Somatic symptoms in primary affective disorder. Presence and relationship to the classification of depression.

The incidence and severity of somatic symptoms were determined in 132 patients with major depressive disorder and 80 normal controls. The role of somatic symptoms was analyzed in relation to the unipolar-bipolar division, Research Diagnostic Criteria (RDC) subtypes, hypersomnia, and appetite increase. The data suggest that the rate and level of somatic symptoms increased with the severity of depression and age, only appetite loss differentiated unipolar from bipolar patients, and the classic somatic symptoms of depression were present in most RDC subtypes and not exclusively associated with the "endogenous" subtype. Hypersomnia or increased appetite identified two overlapping depressive subgroups; patients in both groups were young and characterized by high interpersonal sensitivity. Hypersomniac depressed patients were less anxious and agitated; patients with increased appetite were more hostile and showed a greater decrease in libido than age-matched and sex-matched patients with neither symptom.

Successful treatment of psychotic depression with carbamazepine.

A patient with recurrent episodes of major depression with psychotic features was treated successfully with carbamazepine after unsatisfactory response to other interventions. Since psychotic depression is often difficult to treat with medications, carbamazepine may be a useful addition to the clinician's pharmacological armamentarium.

Comparison of pharmacological treatment response between situational and non-situational depressions.

Fifty-one patients with a primary major depressive disorder preceded by a stressful environmental event were compared for their response to pharmacological treatment with 75 depressives who experienced no stressful life event before illness episodes. There was no difference between the groups in treatment response rates after four and six weeks of treatment respectively.

Migraine headaches and depression.

After taking the lifetime migraine headache histories of 116 patients with major depressive disorder, the authors compared the prevalence of migraine headaches in these depressed patients with the prevalence of migraine reported in four community surveys. There was a trend for the depressed men to experience a higher prevalence of migraine than men in the general population, but the depressed women had a migraine prevalence similar to that of women in the general population. No differences on multiple variables of depressive illness were found between depressed patients with a history of migraine and those with none.

Borderline personality disorder and the MMPI.

Fourteen patients diagnosed as borderline on the basis of the Diagnostic Interview for Borderlines obtained a mean group profile of 8-2-7 similar in configuration, but more elevated than that obtained by a group of 7 diagnostically heterogeneous controls. The borderline patients manifested significantly greater hypochondriasis, depression and hysteria, slightly more schizotypal features, a more deviant self-presentation, and lesser defensiveness. However, considerable heterogeneity in symptomatology was found within the borderline subsample. Further, clinical scales comprised of a higher proportion of relatively subtle and presumably less structured items did not discriminate borderline from control patients more effectively than did those scales made up of a lower proportion of such items. The results offer partial support for the construct validity of the borderline syndrome and for the usefulness of the MMPI in differentiating it from other psychiatric disorders.