Effect of imipramine on norepinephrine and blood pressure in enuretic boys.

The effect of imipramine, desmethylimipramine, and methscopolamine on blood pressure (BP) and plasma norepinephrine (NE) was measured in enuretic boys in a double-blind, placebo-controlled study. Measurements were obtained on the thirteenth day of medication (75 mg at bedtime). The tricyclic drugs induced a rise in diastolic BP as well as an increase in plasma NE but there was no significant relationshhip between the increments in plasma NE and BP. The plasma concentration of drug correlated with the drug-induced BP rise. This is the fifth study to demonstrate a hypertensive effect of tricyclic drugs in children in contrast to the systolic hypotension usually seen in adult patients. It is not clear from our data whether children have different cardiovascular compensatory reflexes or whether they experience a greater stimulant effect from the drug.     

Borderline personality disorder and the chronic headache patient: review and management recommendations

BACKGROUND: Physicians and psychologists who treat headache not infrequently encounter patients with borderline personality disorder (BPD). BPD patients frequently suffer from headache, and often pose special problems in treatment. Few guidelines exist for the management of the BPD headache patient. OBJECTIVES: To provide an overview of current concepts on BPD, including comorbidity, psychopathophysiology, and treatment. To provide an explicit framework for managing borderline behavior in patients with chronic headache. METHODS: A literature review combined with clinical observations from the tertiary treatment of intractable headache in outpatient and inpatient settings. RESULTS: BPD is found in almost 2% of the general population, with increased prevalence in patients with comorbid psychopathology and substance abuse. Severe headaches and migraine appear to be more prevalent in patients with BPD than the general population. A reported history of abuse is common, but must be interpreted with caution. Recent research has found reduced hippocampal volume in women patients with BPD; hypometabolism in the premotor, prefrontal, and anterior cingulate cortex, as well as the thalamic, caudate, and lenticular nuclei; and serotonergic dysfunction. Opioid medications may have an adverse influence on certain clinical features of BPD. Some patients show at least short-term improvement in dissociative behavior when given opioid antagonists. Treatment should combine appropriate pharmacotherapy with ongoing psychotherapy. Early identification of BPD is likely to improve the course of treatment. Treatment often requires explicit contracts, consistent limit-setting, confrontation, and communication between different treating professionals to avoid "splitting." The recognition and management of the doctor's own countertransference is important to successful management. Noncompliant patients may need to be terminated from treatment. CONCLUSIONS: Specific management guidelines and the use of explicit treatment contracts can help sustain patients in treatment, reduce the risk of medication abuse, and minimize distress in the treating professional. Headaches and other symptoms in patients with BPD can be successfully managed over the course of a long-term relationship with clearly defined limits.     

Rat hepatocytes exhibit basolateral Na+/HCO3- cotransport.

Primary cultures and plasma membrane vesicles were used to characterize Na+ and HCO3- transport by rat hepatocytes. Na+ uptake into hepatocytes was stimulated approximately 10-fold by 25 mM extracellular HCO3-.HCO3--stimulated Na+ uptake was saturable, abolished by 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS), and unaffected by amiloride or Cl- removal. Neither propionate nor acetate reproduced this effect of HCO3-. 22Na efflux from preloaded hepatocytes was similarly increased approximately 10-fold by an in greater than out HCO3- concentration gradient. 22Na efflux was also increased by valinomycin and an in greater than out K+ concentration gradient in the presence but not absence of HCO3-. Intracellular pH (pHi) measured with the pH-sensitive fluorochrome 2',7'-bis-(2-carboxyethyl)-5-(and 6-)carboxyfluorescein (BCECF) decreased at a rate of 0.227 (+/- 0.074 SEM) pH units/min when extracellular HCO3- concentration was lowered from 25 to 5 mM at constant PCO2. This intracellular acidification rate was decreased 50-60% in the absence of Na+ or presence of SITS, and was unaffected by amiloride or Cl- removal. Membrane hyperpolarization produced by valinomycin and an in greater than out K+ concentration gradient caused pHi to fall; the rate of fall was decreased 50-70% by Na+ removal or SITS, but not amiloride. An inside positive K+ diffusion potential and a simultaneous out greater than in HCO3- gradient produced a transient 4,4'-diisothiocyano-2,2' disulfonic acid stilbene (DIDS) sensitive, amiloride-insensitive 22Na accumulation in basolateral but not canalicular membrane vesicles. Rat hepatocytes thus exhibit electrogenic basolateral Na+/HCO3- cotransport.     

Adrenergically Mediated Ventricular Fibrillation in Probucol-Treated Dogs: Roles of Alpha and Beta Adrenergic Receptors

A high incidence of sudden death due to ventricular fibrillation (VF) has been observed in dogs under chronic treatment with probucol, a new hypocholesterolemic agent. The present study describes the cardiac electrophysiologic properties of probucol-treated dogs and characterizes the electrophysiological response of these animals to manipulation of the autonomic nervous system. There was no significant difference in the spontaneous sinus cycle length, the QT interval, refractory period of the atrium, ventricle or A-V junction between normal and probucol-treated dogs. Epinephrine produced VF with few and sometimes no preceding premature ventricular extrasystoles. Electrical stimulation of the stellate ganglion induced VF in 16/19 dogs whereas stimulation of the right stellate ganglion induced VF in 1/19 dogs. Phenylephrine induced VF in 0/19 dogs, isoproterenol in 5/19 dogs, but phenylephrine + isoproterenol induced VF in 9/11 dogs in which isoproterenol did not produce VF. alpha (phentolamine) or beta (propranolol) blockade prevented initiation of VF by epinephrine, phenylephrine + is isoproterenol, and left stellate stimulation but alpha blockade did not prevent induction of VF by isoproterenol when isoproterenol alone produced VF. In this nonischemic model, we conclude that left stellate stimulation is a far more potent initiator of VF than right stellate stimulation and that induction of VF appears to require both alpha and beta adrenergic receptor stimulation.     

Patterns of virus-immune T-cell responsiveness. Comparison of (H-2(k) x H-2(b)) {arrow} H-2(b) Radiation Chimeras and negatively selected H-2(b) lymphocytes

Negatively selected H-2K(b)D(b) TDL can be induced to respond strongly to vaccinia virus presented in the context of both H-2K(k) and H-2D(b) when stimulated in irradiated H-2K(k)D(b) recipients. Addition of excess (H- 2K(k)D(b) x H-2K(b)D(b))F1 TDL, which are low responders to H-2D(b)-vaccinia virus, does not obviously suppress the reactivity pattern of the H-2K(b)D(b) T cells. However, lymphocytes from chimeras made by reconstituting H- 2K(b)D(b) mice with (H-2K(k)D(k) × H-2K(b)D(b))F(l) bone marrow cells make little, if any, cytotoxic T-cell response to vaccinia virus when sensitized in H-2K(k)D(b) recipients. We have thus documented one instance where the responder phenotype of T ceils from an F(l) {arrow} parent chimera is not equivalent to that associated with the H-2 type of the parental thymus. Lymphocytes from both the chimera and the H-2K(b)D(b) parent (after negative selection) are tolerant to the H-2K(k) and I-A(k) alloantigens encountered in the recipient, but the chimera T cells are also defective in their response to a neoantigen (vaccinia virus) presented in the context of H-2K(k) which the parental T cells invariably recognize. It is thus possible that at least part of the phenomenology associated with the F(l) {arrow} parent radiation chimeras reflects deletion of repertoire in the context of H-2 antigens present during thymocyte ontogeny on other than radiation-resistant thymic epithelium.     

创伤与复苏:治疗创伤性凝血病需要特殊血液制品

民用创伤中心和部队战斗支持医院正在收治越来越多的严重损伤,他们常规挽救那些在二十年前无法医治的病人。最重要的进展是发展了“紧急”外科学———由于发生凝血病阻碍了正常解剖的恢复,这项技术的发展超越了常规的血库支持治疗。失控的凝血紊乱性出血是创伤后可预防的导致死亡的主要原因。在美国每年大约有1/10的人由于创伤需要医疗处理,其中1/100的人住院,大约1/1000由于创伤后紧急处理而输注了血液制品。2000年,美国马里兰的大学创伤性休克中心(UMSTC),5649人中8%的受伤病人入院后直接根据创伤情况输注红细胞,5%的输注血浆,3%的输注…     

Decoding the genomic tree of life

Genomes hold within them the record of the evolution of life on Earth. But genome fusions and horizontal gene transfer (HGT) seem to have obscured sufficiently the gene sequence record such that it is difficult to reconstruct the phylogenetic tree of life. HGT among prokaryotes is not random, however. Some genes (informational genes) are more difficult to transfer than others (operational genes). Furthermore, environmental, metabolic, and genetic differences among organisms restrict HGT, so that prokaryotes preferentially share genes with other prokaryotes having properties in common, including genome size, genome G+C composition, carbon utilization, oxygen utilization/sensitivity, and temperature optima, further complicating attempts to reconstruct the tree of life. A new method of phylogenetic reconstruction based on gene presence and absence, called conditioned reconstruction, has improved our prospects for reconstructing prokaryotic evolution. It is also able to detect past genome fusions, such as the fusion that appears to have created the first eukaryote. This genome fusion between a deep branching eubacterium, possibly an ancestor of the cyanobacterium and a proteobacterium, with an archaeal eocyte (crenarchaea), appears to be the result of an early symbiosis. Given new tools and new genes from relevant organisms, it should soon be possible to test current and future fusion theories for the origin of eukaryotes and to discover the general outlines of the prokaryotic tree of life.     

Shear stress activation of platelet glycoprotein IIb/IIIa plus von Willebrand factor causes aggregation: filter blockage and the long bleeding time in von Willebrand's disease

The article explores the finding that high shear alone applied to normal, native blood results in platelet aggregation. A filter with tortuous capillary-sized channels permits a study of the effect of shearing forces at different pressures. Native, heparinized, citrated and EDTA blood and platelet-rich plasma (PRP) were forced through the filter. Normal and von Willebrand's blood were studied, as were the effects of antibodies to platelet glycoproteins (GPr) and to von Willebrand's factor (vWf) and of "membrane-active" drugs. Normally, the filter blocked at 40 mmHg but not at 5 mmHg. Transmission electronmicroscopy of the filter at 40 mmHg showed blockage by platelet aggregates. Initially, the mean transit time through the filter was 8 milliseconds. Platelet retention in the filter occurred in two phases. From 0 to 3 seconds, only high-shear, vWf, and GPrIIb/IIIa were required. From 10 to 20 seconds, retention presumably involved these three attributes, but divalent cations were also essential. Only this phase was inhibited by some membrane-active drugs. ADP- and thrombin- induced aggregation requires GPrIIb/IIIaand fibrinogen. Shear-induced blocking of the filter by blood with a normal concentration of fibrinogen requires GPrIIb/IIIa and vWf. This indicates a different type of exposure of GPrIIb/IIIa. The long bleeding time in vW disease highlights the absolute requirement for vWf and emphasizes the difference in exposure of GPrIIb/IIIa induced by shear stress. Evidently, a process similar to that occurring in the filter is required in normal capillary hemostasis.     

The relationship between synovitis and erosions in rheumatoid arthritis

If clinically evident synovitis causes erosions, then the two should be highly correlated within individual joints. Separate hand joints (total 2064) were examined for the presence of synovitis (the simultaneous presence of soft-tissue swelling and tenderness) on nine occasions over 2 yr. The cumulative synovitis score was compared to the change in the Larsen score over the same period. The mean correlation between synovitis and erosion progression was r = 0.248 (explained variance = 6%). Of the 216 joints which showed progressive X-ray damage, 44% had a cumulative synovitis score of < 3. When all the joints of one hand were taken together, the correlation was increased to r = 0.418 and for all the joints of both hands taken together it was further increased to r = 0.424. These results argue against there being a direct causal relationship between clinically inflamed synovitis and erosions in rheumatoid arthritis, and question the assumption that erosions and the signs of synovitis represent the same pathological process.