Implementation of the Anemia Guidelines

A study of 100 patients who made a severe suicide attempt suggested that the managed care criteria often applied for approving admission to hospitals for potentially suicidal patients were not, in fact, predictive of features seen in patients who actually made such attempts. Severe anxiety, panic attacks, a depressed mood, a diagnosis of major affective disorder, recent loss of an interpersonal relationship, recent abuse of alcohol or illicit substances coupled with feelings of hopelessness, helplessness, worthlessness, global or partial insomnia, anhedonia, inability to maintain a job, and the recent onset of impulsive behavior were excellent predictors of suicidal behavior. The presence of a specific suicide plan or suicide note were not. Patients with managed care were overrepresented by 245% in the study.     

Conservative surgical therapy for penile and urethral carcinoma

OBJECTIVES: Invasive penile and urethral tumors are traditionally treated with aggressive excision that requires involved organ and adjacent organ sacrifice. An alternative approach seeks to completely excise the tumor with adequate margins while preserving form and function of the organ. We present 6 patients who underwent such organ-sparing surgery. METHODS: Six selected cases (4 penile and 2 urethral) are presented with operative photographs and pertinent data. RESULTS: Three distal tumors of the penis were treated with excision limited to the glans with histopathologic findings of verrucous carcinoma, melanoma, and angiosarcoma. One patient with squamous cell carcinoma of the distal shaft refused partial penectomy and underwent a local wedge resection. A patient with locally advanced bulbourethral transitional cell carcinoma (TCC) refused cystourethrectomy and underwent an anterior urethrectomy and perineal urethrostomy. A 48-year-old woman with an adenocarcinoma contained in a very distal urethral diverticulum underwent simple diverticulectomy and excision of distal urethra. Postoperative voiding and sexual function were well preserved. Follow-up was 12 to 48 months. The patient with angiosarcoma died of lung metastases at 48 months with no local disease, and the patient with bulbourethral TCC developed pelvic disease at 12 months with no local recurrence and died of metastases at 25 months. CONCLUSIONS: Organ-sparing surgery is appropriate in selected patients on the basis of stage and location, high risk of distant failure, and patient disposition. Close follow-up is necessary. Comanagement with reconstructive and oncologic specialists optimizes results and outcomes.     

Role of the cytoskeleton in calcium signaling in NIH 3T3 cells. An intact cytoskeleton is required for agonist-induced [Ca2+]i signaling, but not for capacitative calcium entry

Treatment of NIH 3T3 cells with cytochalasin D (10 microM, 1 h at 37 degrees C) disrupted the actin cytoskeleton and changed the cells from a planar, extended morphology, to a rounded shape. Calcium mobilization by ATP or by platelet-derived growth factor was abolished, while the ability of thapsigargin (2 microM) to empty calcium stores and activate calcium influx was unaffected. Similar experiments with nocodazole to depolymerize the tubulin network yielded identical results. Platelet-derived growth factor induced an increase in inositol phosphates, and this increase was undiminished in the presence of cytochalasin D. Therefore, the blockade of agonist responses by this drug does not result from decreased phospholipase C. Injection of inositol 1,4,5-trisphosphate (IP3) released calcium to the same extent in control and cytochalasin D-treated cells. Confocal microscopic studies revealed a significant rearrangement of the endoplasmic reticulum after cytochalasin D treatment. Thus, disruption of the cytoskeleton blocks agonist-elicited [Ca2+]i mobilization, but this effect does not result from a lower calcium storage capacity, impaired function of the IP3 receptor, or diminished phospholipase C activity. We suggest that cytoskeletal disruption alters the spatial relationship between phospholipase C and IP3 receptors, impairing phospholipase C-dependent calcium signaling. Capacitative calcium entry was not altered under these conditions, indicating that the coupling between depletion of intracellular calcium stores and calcium entry does not depend on a precise structural relationship between intracellular stores and plasma membrane calcium channels.     

The role of the active site cysteine in catalysis by type 1 iodothyronine deiodinase

Type 1 iodothyronine deiodinase (deiodinase 1) is a selenoenzyme that converts the prohormone T4 to the active thyroid hormone T3 by outer ring deiodination or to the inactive metabolite rT3 by inner ring deiodination. Although selenocysteine has been demonstrated to be essential for the biochemical profile of deiodinase 1, the role of a highly conserved, active site cysteine (C124 in rat deiodinase 1) has not been defined. The present studies examined the effects of a Cys124Ala mutation on rat deiodinase 1 enzymatic function and substrate affinity. At a constant 10-mM concentration of dithiothreitol (DTT), the C124A mutant demonstrated a 2-fold lower apparent maximal velocity (Vmax) and Km for rT3 (KmrT3) than the wild type for outer ring deiodination, whereas the Vmax/Km ratio was unchanged. Similarly, the apparent Vmax and KmT3 sulfate for inner ring deiodination were 2-fold lower in the C124A mutant relative to those in the wild type, with no change in the Vmax/Km ratio. The C124A mutant exhibited ping-pong kinetics in the presence of DTT, and substitution of the active site cysteine increased the KmDTT by 14-fold relative to that of the wild-type enzyme, with no significant effects on KmrT3 or Vmax. The C124A mutant was inhibited by propylthiouracil in an uncompetitive fashion and exhibited a 2-fold increase in K(i)propylthiouracil compared with that of the wild type. KmrT3 was also reduced for the C124A mutant when 5 mM reduced glutathione, a potential physiological monothiol cosubstrate, was used in outer ring deiodination assays. These results demonstrate that thiol cosubstrate interactions with C124 in type 1 deiodinase play an important role in enhancing catalytic efficiency for both outer and inner ring deiodination.     

Diabetic gastroparesis: is tube feeding an alternative?

A woman aged 26 with long-standing insulin-dependent diabetes mellitus displayed recurrent periods of nausea, vomiting, abnormal blood sugar levels, weight loss and poor physical condition in spite of a diet and use of propulsive agents. Scintigraphy revealed decelerated gastric evacuation for solid and liquid nutrients. The patient recovered after insertion of a percutaneous endoscopic gastrostomy (PEG) catheter. Diabetic gastroparesis is associated with a vicious circle in which delayed gastric emptying leads to poor glucose regulation with frequent hyperglycaemia, which in its turn adversely affects gastric emptying. Treatment should be aimed at improvement of the gastric motility (for instance by propulsive agents), more accurate glucose regulation and nutritional counselling. If this fails to produce improvement, tube feeding via a permanent nasoduodenal tube or via a PEG catheter constitutes an acceptable alternative for oral nutrition.     

Stenosis of the tubular neck: a possible mechanism for progressive renal failure

OBJECTIVE: To study the influence of continuous administration of heparin on platelet function in intensive care patients. DESIGN: Prospective, serial investigation. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. PATIENTS: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. INTERVENTIONS: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). MEASUREMENTS AND RESULTS: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 mumol/l), collagen (10 micrograms/ml), and epinephrine (25 mumol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4-10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e.g., epinephrine-induced maximum platelet aggregation:-45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e.g., ADP-induced maximum platelet aggregation: +42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. CONCLUSIONS: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.     

Preclinical evaluation of Seprafilm bioresorbable membrane

OBJECTIVE: To characterize Seprafilm bioresorbable membrane and assess its efficacy and safety in reducing adhesions. DESIGN: In vitro and animal studies designed to provide precise control of tissue trauma and closely approximate clinically relevant conditions in abdominal surgery. SETTING: Experimental laboratories, USA. SUBJECTS: Experimental animals, principally rats and rabbits. INTERVENTIONS: The rat cecal abrasion or sidewall injury model evaluated the efficacy of seprafilm in the presence of blood and irrigation solutions, in multiple layers, under ischemic conditions, and in adhesion reformation. A rabbit anastomosis model tested the effect of the membrane on wound healing, and a series of challenge tests determined its toxicology, immunogenicity, and biocompatibility. MAIN OUTCOME MEASURES: Incidence and severity of adhesions; mutagenicity; pyrogenicity; irritation effects; systemic toxicity. RESULTS: Seprafilm significantly reduced the number of cecal adhesions (p < 0.001) and the number of animals with severe adhesions (p < 0.001) when compared with nontreated controls, even in the presence of bleeding. The membrane also significantly decreased the number of animals with any adhesions (p < 0.001). Seprafilm maintains efficacy when used with excess irrigation solutions, when layered, and under ischemic conditions. Among rats tested for adhesion reformation, the treated group had a significantly larger proportion of adhesion-free animals than the untreated group, 72% versus 28%, (p = 0.007). Seprafilm did not impair wound healing in anastomosis and is nontoxic, nonmutagenic, nonimmunogenic, nonpyrogenic, nonirritating, and biocompatible. CONCLUSION: Preclinical studies have shown that Seprafilm is safe and effective in reducing postsurgical adhesions. Seprafilm meets the requirements of an ideal barrier and can be a useful adjuvant in abdominal and pelvic surgery.