Hereditary antithrombin III deficiency and neuraxial anaesthesia.

Antithrombin III (ATIII) deficiency offers unique challenges to the anaesthetist in the perioperative setting due to the inherent thrombophilia, the anticoagulant therapies instituted and replacement of the deficient intrinsic natural anticoagulant. A particular challenge is the use of intrathecal anaesthesia, which requires a safe level of coagulation at the time of subarachnoid puncture. We describe the use of intrathecal anaesthesia on two occasions in a patient with ATIII deficiency who received human-derived ATIII concentrate as part of a perioperative anticoagulant regimen. The patient sustained no thrombotic or bleeding events. Our experience suggests that ATIII deficiency does not preclude the use of regional anaesthetic techniques so long as there is timely referral to a multidisciplinary perioperative service for anticoagulant management and that ATIII concentrate is used to ensure safe levels of ATIII throughout the perioperative period.

Hypertonic saline in paediatric traumatic brain injury: a review of nine years' experience with 23.4% hypertonic saline as standard hyperosmolar therapy.

We describe the protocolised use of 23.4% hypertonic saline solution (HTS) for intracranial hypertension in the context of traumatic brain injury in the paediatric population. This study represents the largest published data on the use of 23.4% HTS in the paediatric population. In this retrospective cohort, we focus on the efficacy, biochemical and metabolic consequences of 23.4% HTS administration in a Level 1 paediatric trauma centre. Mortality in the first seven days was 6% (2/32) with a mean intensive care unit length-of-stay of ten days (range 2 to 25, standard deviation [SD] 6). All-cause hospital mortality was 6%, with no deaths after the seven-day study period. Mean intracranial pressure (ICP) response to HTS was 10 mmHg (range 1 to 30, SD 8). For biochemistry data, the mean highest daily serum sodium was 148 mmol/l (139 to 161, SD 6), mean highest serum chloride was 115 mmol/l (range 101 to 132, SD 8) with matched mean serum base excess of -1.5 mmol/l (range 2 to -8, SD 3) and mean peak serum creatinine was 73 mmol/l (range 32 to 104, SD 32). Glasgow outcome scores of >3 (independent function) were achieved in 74% of patients. We describe the use of 23.4% HTS, demonstrating it to be a practical and efficacious method of delivering osmoles and may be advantageous in minimising total fluid volume. Thus, the bolus versus infusion debate may best be served via combining both approaches.

[Adenocarcinoma of the stomach and neuroendocrine carcinoma of the colon in a 45-year-old male patient suffering from common variable immunodeficiency (CVID) and ulcerative colitis]. / Adenokarzinom des Magens und neuroendokrines Kolonkarzinom bei einem 45-jährigen Patienten mit Common Variable Immunodeficiency (CVID) und Colitis ulcerosa.

Common variable immunodeficiency (CVID) is the most common primary antibody deficient syndrome in adults. Among the broad spectrum of clinical manifestations are recurrent infections, allergies, autoimmune, tumour, pulmonary, liver and gastrointestinal diseases. Here we report the case of a 45-year-old male patient, who has been suffering from ulcerative colitis - likewise recognised as a CVID-associated disease - for many years. He was admitted to our clinic with a rapid progressive reduction of his general condition and a loss of weight. Diagnostic work-up revealed adenocarcinoma of the stomach as well as an undifferentiated neuroendocrine carinoma of the colorectum at the rectosigmoidal junction. Curative resection of the distal stomach and proctolcolectomy were performed. To date, the pathogenesis of the association of many diseases with CVID is still ambiguous. Yet, there is no doubt about the significantly higher incidence of e.g., inflammatory bowel disease or gastric cancer in patients with CVID. Our case highlights that in patients with CVID and obscure deterioration of their general health condition a careful search for especially malignant complications is mandatory although to date there are no precise recommendations for screening.

[Intracerebral lesions after TNF-alpha inhibitor therapy with pre-existing sarcoidosis and sacroiliitis]. / Zerebrale Rundherde unter TNF-α-Blocker-Therapie bei vorbestehender Sarkoidose und Sakroiliitis.

This article reports the case of a 55-year-old man who presented with aphasia caused by intracerebral lesions and had a history of pulmonary sarcoidosis. Due to nonsteroidal anti-inflammatory drug-resistant spondyloarthritis TNF-alpha inhibitor treatment was started after a negative tuberculosis screening. Subsequently the patient developed pulmonary tuberculosis and cerebral tuberculoma reactivated by the TNF-alpha inhibitor therapy accompanied by pulmonary sarcoidosis with sacroiliitis and oligoarthritis. This case report emphasises the risk of atypical tuberculosis infections under TNF-alpha inhibitors despite negative results of tuberculosis screening.

Glyburide/metformin combination product is safe and efficacious in patients with type 2 diabetes failing sulphonylurea therapy.

AIM: To compare the efficacy, safety and tolerability of a fixed combination glyburide/metformin preparation with those of glyburide or metformin alone in patients with type 2 diabetes inadequately controlled by sulphonylurea, diet and exercise. METHODS: In this 16-week, randomized, double-blind, parallel group study, 639 patients with inadequate glycaemic control on at least half-maximal dose of sulphonylurea were randomly assigned to: glyburide 10 mg b.i.d. (n = 164); metformin 500 mg (n = 153); glyburide/metformin 2.5 mg/500 mg (n = 160); or glyburide/metformin 5 mg/500 mg (n = 162). Titration was allowed to maximum doses of 2000 mg for metformin or 10 mg/2000 mg and 20 mg/2000 mg for glyburide/metformin 2.5 mg/500 mg and 5 mg/500 mg respectively. The primary outcome measure was HbA1c level after 16 weeks; secondary end-points included fasting and 2-h post-prandial plasma glucose. Adverse events (AEs) were recorded and summarized by treatment group. RESULTS: Both strengths of glyburide/metformin equally reduced mean HbA1c by 1.7% more than did glyburide alone (p < 0.001), and by 1.9% more than did metformin alone (p < 0.001). Final mean fasting plasma glucose concentrations were also lower in both glyburide/metformin groups than in the glyburide (-2.8 mmol/l, -51.3 mg/dl; p < 0.001) and metformin groups (-3.6 mmol/l, -64.2 mg/dl; p < 0.001). Safety and tolerability were similar across all treatment groups, except for a higher incidence of gastrointestinal AEs in the metformin monotherapy group, and more patients reporting mild or moderate symptoms of hypoglycaemia while taking glyburide/metformin. CONCLUSIONS: Both glyburide/metformin tablet strengths produced, with equal efficacy, significantly better glycaemic control than monotherapy with either agent. These data also confirm that glycaemic efficacy does not require maximal sulphonylurea doses in combination with metformin.

Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes.

OBJECTIVE: To evaluate whether simultaneous initial treatment of both insulin resistance and impaired beta-cell insulin secretion with glyburide/metformin tablets is superior to monotherapy with each component agent. RESEARCH DESIGN AND METHODS: In this randomized, parallel-group, placebo-controlled, multicentre study, 806 patients with type 2 diabetes (mean duration, 3 years) who had failed diet and exercise were randomly assigned to 4 weeks of therapy with placebo, glyburide 2.5 mg, metformin 500 mg, glyburide/metformin 1.25/250 mg, or glyburide/metformin 2.5/500 mg once daily. Doses were then titrated over 8 weeks based on glycaemic response. The primary outcome measure was change from baseline in mean HbA1c after 20 weeks. Changes in fasting plasma glucose, lipids and body weight were also assessed along with 2-h postprandial glucose and insulin values after a standardized meal. RESULTS: At week 20, patients taking glyburide/metformin 1.25/250 mg or 2.5/500 mg tablets had greater reductions in HbA1c levels (-1.48% and -1.53% respectively) compared with placebo (-0.21%; both p < 0.001), glyburide (-1.24%; p = 0.016 and p = 0.004 respectively) or metformin (-1.03%; both p < 0.001). Fasting plasma glucose concentrations were reduced more in both glyburide/metformin groups compared with placebo and metformin (p < 0.001); patients in both combination therapy groups also had significantly lower postprandial glucose concentrations compared with placebo, glyburide and metformin. CONCLUSIONS: Initial combination treatment with glyburide/metformin tablets produces greater improvements in glycaemic control than either glyburide or metformin monotherapy. The superiority of initial therapy with glyburide/metformin tablets may arise from simultaneous treatment of both pathophysiological defects of type 2 diabetes.

NCCN Practice Guidelines for Cancer-Related Fatigue.

These guidelines propose a treatment algorithm in which patients are evaluated regularly for fatigue, using a brief screening instrument, and are treated as indicated by their fatigue level. The algorithm's goal is to identify and treat all patients with fatigue that causes distress or interferes with daily activities or functioning. Management of fatigue begins with primary oncology team members who perform the initial screening and either provide basic education and counseling or expand the initial screening to a more focused evaluation for moderate or higher levels of fatigue. At this point the patient is assessed for the five primary factors known to be associated with fatigue: pain, emotional distress, sleep disturbance, anemia, and hypothyroidism. If any of these conditions are present, it should be treated according to practice guidelines, and the patient's fatigue should be reevaluated regularly. If none of the primary factors is present or the fatigue is unresolved, a more comprehensive assessment is indicated--with referral to other care providers as appropriate. The comprehensive assessment should include a thorough review of systems, review of medications, assessment of comorbidities, nutritional/metabolic evaluation, and assessment of activity level. Management of fatigue is cause-specific when conditions known to cause fatigue can be identified and treated. When specific causes, such as infection, fluid and electrolyte imbalances, or cardiac dysfunction, cannot be identified and corrected, nonpharmacologic and pharmacologic treatment of the fatigue should be considered. Nonpharmacologic interventions may include a moderate exercise program to improve functional capacity and activity tolerance, restorative therapies to decrease cognitive alterations and improve mood state, and nutritional and sleep interventions for patients with disturbances in eating or sleeping. Pharmacologic therapy may include drugs such as antidepressants for depression or erythropoietin for anemia. A few clinical reports of the use of corticosteroids and psychostimulants suggest the need for further research on these agents as a potential treatment modalities in managing fatigue. Basic to these interventions, the effective management of cancer-related fatigue involves an informed and supportive oncology care team that assesses patients' fatigue levels regularly and systematically and incorporates education and counseling regarding strategies for coping with fatigue (Johnson, 1999), as well as using institutional fatigue management experts for referral of patients with unresolved fatigue.

Differences in fatigue by treatment methods in women with breast cancer.

PURPOSE/OBJECTIVES: To investigate the differences between various cancer therapies (radiation, hormonal, chemotherapy, and their combinations) and the specific dimensions of fatigue (affective meaning, behavioral/severity, cognitive/mood, and sensory). DESIGN: Descriptive, cross-sectional, mailed survey design. SAMPLE AND SETTING: Data were collected from women who were breast cancer survivors and members of a nonprofit educational organization in the North-east. Criteria for this study included no self-reported disease recurrence, and treatment was within 18 months prior to the mailed survey (N = 322). The typical participant was middle-aged (mean = 52.2; SD = 10.3), Caucasian (93%), postmenopausal (55%), and diagnosed with cancer 2.42 (SD = 2.6) years prior to the study. METHODS: Secondary data analysis from a study using the Piper Fatigue Scale. VARIABLES: Level of fatigue. FINDINGS: Significant differences were found by treatment in total fatigue scores (p < 0.03) and cognitive/mood scores (p < 0.05). Women who received combination therapy had the highest fatigue scores (mean = 4.8; SD = 2.0); those who received only radiation therapy had the lowest fatigue scores (mean = 2.7; SD = 2.0). CONCLUSIONS: Fatigue in breast cancer survivors varies by type of cancer therapy. Future studies are needed to investigate the relationships between fatigue and hormonal therapy, and they need to be designed to examine changes over time. IMPLICATIONS FOR NURSING PRACTICE: Study findings advance knowledge about fatigue in women with breast cancer and aid nurses in providing anticipatory guidance for women undergoing different treatment regimens.

The revised Piper Fatigue Scale: psychometric evaluation in women with breast cancer.

PURPOSE/OBJECTIVES: To confirm the multidimensionality of the Piper Fatigue Scale (PFS) and to reduce the total number of PFS items without compromising reliability and validity estimates. DESIGN: Methodologic, part of a larger, cross-sectional, mailed survey design study. SETTING: Urban and suburban area in the northeast United States. SAMPLE: As part of the larger study, 2,250 surveys were distributed to women survivors of breast cancer who were on a mailing list for the educational organization Living Beyond Breast Cancer, 715 surveys (32%) were returned. Of these, 382 women met this methodologic study's criteria for having completed each of the 40 items on the PFS. The average respondent was 50 years old, postmenopausal, and treated with combination cancer therapy. METHODS: Principal axes factor analysis with oblique rotation. MAIN RESEARCH VARIABLES: Fatigue factors/subscales. FINDINGS: Five factors/subscales were identified initially. Because the fifth factor contained only two items (ability to bathe/wash and ability to dress), these items and the associated factor/subscale were dropped from the final solution. An additional nine items, not loading on any factor (> 0.40), also were dropped. The remaining items and factors/subscales were reviewed to ensure that the criteria were met: a pattern of inter-item correlations between 0.30-0.70; a minimum number of five or more items/subscale; standardized alpha for the subscales and total scale of at least 0.89; and absence of gender-specific items. CONCLUSIONS: The revised version of the PFS consists of 22 items and four subscales: behavioral/severity (6 items), affective meaning (5 items), sensory (5 items) and cognitive/mood (6 items). Standardized alpha for the entire scale (n = 22 items) is 0.97, indicating that some redundancy still may exist among the items. Additional revisions await further testing. IMPLICATIONS FOR NURSING PRACTICE: As fatigue is acknowledged to be the most frequent symptom experienced by patients with cancer, accurate measurement and assessment is essential to advance not only the science of fatigue but, most importantly, to evaluate the efficacy of intervention strategies on patient and family outcomes.

Diagnosis and management of osteoporosis.

Risk factors for osteoporosis, bone densitometry, and biochemical testing can identify those most in need of preventive measures to optimize calcium metabolism and reduce bone loss. Treatment options for established disease are evaluated.

Clinical insights from the etiopathology of osteoporosis.

Bone resorption may be stimulated by increased parathyroid hormone secretion, certain cytokines, and other bone-resorbing mediators. Low serum calcium levels promote parathyroid hormone secretion, and estrogen deficiency is associated with a rise in cytokine production and activity. An abnormal proliferation of mast cells may also release cytokines, heparin, and other mediators of bone resorption.

Insulin resistance, hypersecretion of LH, and a dual-defect hypothesis for the pathogenesis of polycystic ovary syndrome.

OBJECTIVE: To review the literature dealing with the roles of insulin resistance and elevated LH levels in the development of the polycystic ovary syndrome and to outline a new hypothesis of the pathogenesis of this disorder. DATA SOURCES: We reviewed articles on the topics of insulin resistance, elevated LH levels, and polycystic ovary syndrome that were contained in the CD-PLUS MEDLINE system data base for years 1976-1994. METHODS OF STUDY SELECTION: Ninety-one original reports published in English-language, peer-reviewed biomedical journals were selected. DATA EXTRACTION AND SYNTHESIS: The selected studies were reviewed critically and their conclusions were evaluated. The available literature indicates that insulin resistance and increased LH secretion are frequent features of polycystic ovary syndrome and may be important in its pathogenesis. It appears that both the amplitude and the frequency of LH pulses are increased in this disorder. Although the causes of these abnormalities of LH secretion are unknown, they could be either primary (due to increased sensitivity of LH secretion to GnRH) or secondary (due to the effects of sex steroids on LH secretion). The cause of insulin resistance in polycystic ovary syndrome also is unknown. It most likely results from a post-binding defect in the insulin action pathway. There is both in vitro and in vivo evidence that elevated LH and hyperinsulinemia act synergistically to enhance ovarian growth, androgen secretion, and ovarian cyst formation. CONCLUSIONS: Based on the available literature, we propose a "dual-defect" hypothesis of polycystic ovary syndrome. We suggest that in a significant subset of patients, this disorder may be caused by a conjunction of two independent genetic defects: one that produces elevated LH secretion and another that produces insulin resistance. Thus, polycystic ovary syndrome develops as a result of the synergistic action of increased LH levels and hyperinsulinemia on the ovary. This working hypothesis may serve as a useful guide for further studies of the pathogenesis of polycystic ovary syndrome.

Lymphoma of the thyroid mimicking thyroiditis in a patient with the acquired immune deficiency syndrome.

A 35-year-old man with AIDS and a history of a remission from the lymphoma of the right tonsil (previously treated with chemotherapy and radiation) presented with a variety of clinical, laboratory and radiological findings strongly suggestive of subacute thyroiditis. Fine needle aspiration biopsy failed to establish the tissue diagnosis. Pathological examination of the thyroid tissue obtained during an open surgical biopsy revealed a lymphoma. Appropriate chemotherapy produced a rapid clinical and laboratory improvement manifested by the reduction of the goiter and restoration of a euthyroid state. Hypothyroidism subsequently developed, but therapy with thyroid hormone resulted in a rapid normalization of thyroid function tests. The patient expired because of AIDS-related complications.