Laboratory-Confirmed Metformin-Associated Lactic Acidosis

Introduction Metformin is considered the first line oral hypoglycaemic agent for the treatment of type 2 diabetes. We report three cases of prospectively identified laboratory confirmed metformin-associated lactic acidosis admitted to our intensive care unit. Case 1 72-year-old female presented with lactic acidosis; pH 6.7, lactate 22.6mmol/L with elevated Metformin levels of 4.9mg/L. Case 2 56-year-old female presented with lactic acidosis; pH 7.2 and lactate 14.8mmol/L. Metformin levels elevated at 3.9mg/L. Case 3 72-year-old female presented with lactic acidosis, pH 6.95 and lactate of 27.6mmol/L with elevated Metformin levels of 48.7mg/L. Results All three cases were admitted to the intensive care unit to receive supportive care. Despite CVVHD, two patients died. Discussion Metformin is considered the first line oral hypoglycaemic agent. Confirmation of this diagnosis often proves difficult due to the scarcity of laboratory testing. Our case series highlights the issues of inappropriate prescription in specific patient populations.

Measuring brain stem and cerebellar damage in parkinsonian syndromes using diffusion tensor MRI.

OBJECTIVE: To use diffusion tensor MRI to quantify and compare degeneration of the pons and cerebellar peduncles in multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and Parkinson disease (PD) and to relate changes in diffusion measures to clinical features and localized atrophy. METHODS: We used a region-of-interest approach to measure changes in fractional anisotropy and mean diffusivity in the middle cerebellar peduncles, decussation of the superior cerebellar peduncles, and pons in 17 patients with MSA, 17 with PSP, 12 with PD, and 12 healthy volunteers. We also evaluated atrophy of the cerebellar peduncles and pons on T2-weighted magnetic resonance images in patients with MSA and PSP. RESULTS: In MSA, fractional anisotropy was markedly reduced in the middle cerebellar peduncles, and mean diffusivity increased both here and in the pons compared with other groups, whereas in PSP, mean diffusivity was strikingly increased in the decussation of superior cerebellar peduncles. Cerebellar ataxia was related to mean diffusivity in the middle cerebellar peduncles (r = 0.71, p = 0.001) and pons (r = 0.60, p = 0.01) in MSA. Diffusion measures were related to localized atrophy in both MSA and PSP. CONCLUSIONS: Diffusion tensor MRI can be used to quantify neurodegenerative processes in different brain stem and cerebellar structures in multiple system atrophy and progressive supranuclear palsy during life, and may have diagnostic value. Larger studies of early, undifferentiated parkinsonian syndromes are indicated to provide estimates of the relative diagnostic value of diffusion measures, atrophy measures, and visual assessment of scans.

The allelic modulation of apolipoprotein E expression by oestrogen: potential relevance for Alzheimer's disease.

BACKGROUND: The epsilon4 allele of the apolipoprotein E (APOE) gene is a major genetic risk factor for Alzheimer's disease but appears to be associated with greater risk in women than in men. Some studies suggest that the level of APOE may of its own modulate the risk for Alzheimer's disease. Sex differences and an apparent benefit of oestrogen therapy suggest a role for oestrogen. APOE expression is influenced by oestrogen and oestrogen therapy may not benefit women bearing an APOE epsilon4 allele. These findings suggest an interaction between oestrogen and APOE in the Alzheimer's disease process. AIM: To explore the hypothesis that APOE expression is regulated by a genomic mechanism and is modified by the polymorphisms in APOE associated with risk for Alzheimer's disease. METHODS: In vitro binding studies were undertaken between oestrogen receptors and fragments of the human APOE gene. APOE gene expression was studied to investigate a possible functional interaction. RESULTS: APOE epsilon2/epsilon3/epsilon4 coding and -219 G/T promoter polymorphisms influenced binding to the oestrogen receptor and altered transcriptional activity in response to oestrogen. CONCLUSIONS: An allele dependent modulation of oestrogen induced regulation of APOE might be involved in the increased risk for Alzheimer's disease in women bearing an epsilon4 allele.

Molecular genetic approaches to puerperal psychosis.

Puerperal psychosis, an episode of mania or psychosis precipitated by childbirth follows approximately one in 1000 deliveries. The evidence of clinical, outcome and genetic studies supports the hypothesis that the majority of puerperal psychotic episodes are manifestations of an affective disorder diathesis with a puerperal trigger. Furthermore the available evidence supports the hypothesis that genes are involved in susceptibility to both diathesis and trigger. For complex genetic disorders such as affective illness there are marked benefits in focussing on a homogeneous subtype which allows a subset of hypotheses to be tested. Molecular genetic studies of puerperal psychosis provide an excellent example of this strategy, allowing a hierarchy of hypotheses concerning the involvement of neurosteroid pathways in pathophysiology to be tested. Puerperal psychosis results in considerable suffering to a woman and her family. Elucidating the pathophysiological basis of this disorder will lead to better prevention and treatment and, it is anticipated, inform research on affective disorders more generally.

Facilitating cancer pain control in the home: opioid-related issues.

The basic principles of pain management are the same whether the patient is in an acute care setting, their home, or a long-term care facility. Wherever the setting, pain management is part of the comprehensive care for the cancer patient. Successful therapy depends on a clear definition of treatment goals, an informed patient and family, collaboration and effective communication between the physician, home care nurse, patient and family, and ongoing monitoring to ensure effectiveness of pain relief measures. Careful discharge planning to ensure appropriate home care for the patient with pain and their family is critical.

Current management of opioid-related side effects.

The optimal management of opioid-related side effects is hampered by a lack of comparative studies of management strategies. The prevalence of such side effects is influenced by the extent of disease, the patient's age, the presence of coexistent renal and hepatic disease, pulmonary disease, and cognitive dysfunction, a prior opioid history, use of polypharmacy, dose of opioid drug being administered, and the route of administration. The most common opioid-related side effects are constipation, sedation, nausea, vomiting, and cognitive disturbance. Less frequent side effects include urinary retention, perceptual distortion, respiratory depression, and myoclonus. In an era emphasizing quality of life in cancer care, clinicians need to be aware of (1) factors that influence the prevalence of opioid-related side effects, (2) effective management strategies, and (3) how to recognize when symptoms are opioid related as opposed to caused by other etiologies, such as the patient's disease process or treatment approaches. The use of validated instruments and repeated assessment enhances such an evaluation and subsequent treatment. This article delineates the current optimal management of opioid-related nausea and vomiting, constipation, cognitive side effects, myoclonus, and respiratory depression.

Terminal care and bereavement.

Care of patients at the end of life requires a high level of clinical vigilance, compassion and skill. The involvement of the patient's primary neurologist in end-of-life care and into bereavement can be an invaluable comfort to the patient and family. An understanding of the techniques for assessing and anticipating patient and family needs and knowledge of the resources available is essential if the neurologist is to provide guidance in their care.

Molecular genetic studies of bipolar disorder and puerperal psychosis at two polymorphisms in the estrogen receptor alpha gene (ESR 1).

A number of lines of evidence point to the possible involvement of estrogen pathways in the pathophysiology of bipolar disorder in general and puerperal psychosis in particular. There is strong evidence from clinical, follow-up, and genetic studies to support the hypothesis that most cases of puerperal psychosis are manifestations of an affective disorder diathesis with a puerperal trigger and that genes influence susceptibility to both diathesis and trigger. The nature of the trigger is unknown but in view of the abrupt onset at a time of major physiological change it is widely believed that biological, probably hormonal, mechanisms are of paramount importance, with estrogen receiving the most attention to date. We have undertaken a case control association study of bipolar disorder and puerperal psychosis at two known polymorphisms within the estrogen receptor alpha gene (ESR 1) in a sample of 219 unrelated bipolar probands and 219 controls. We could exclude these polymorphisms from an important contribution to susceptibility to bipolar disorder with a high level of confidence. We found no support for the hypothesis that they contribute specific susceptibility to the puerperal trigger, but due to the small numbers of puerperal probands (n = 26) no firm conclusions can be drawn regarding their involvement in puerperal psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:850-853, 2000.

Variation at the serotonin transporter gene influences susceptibility to bipolar affective puerperal psychosis.

Up to half of parous females with bipolar disorder (manic depression) develop an episode of severe psychiatric disturbance, usually called puerperal psychosis, within a few days of giving birth. We report significant evidence (p<0.003) that variation at the serotonin transporter gene exerts a substantial (odds ratio=4) and important (population attributable fraction=69%) influence on susceptibility to such episodes.

Multidisciplinary care of the terminally ill patient.

This article discusses sedation, the assessment and management of physical symptoms, and symptom-assessment scales for the terminally ill patient. The evaluation of the ability of the family or community to care for a terminally ill patient in pain also is discussed.

NCCN Practice Guidelines for Cancer Pain.

The overall approach to pain management encompassed in these guidelines is comprehensive. It is based on objective pain assessments, utilizes both pharmacologic and nonpharmacologic interventions, and requires continual reevaluation of the patient. The NCCN Cancer Pain Practice Guidelines Panel believes that cancer pain can be well controlled in the vast majority of patients if the algorithms presented are systematically applied, carefully monitored, and tailored to the needs of the individual patient.

Determinants of the willingness to endorse assisted suicide. A survey of physicians, nurses, and social workers.

The authors surveyed 1,137 physicians, nurses, and social workers (overall response = 48%) to characterize the willingness to endorse assisted suicide. Willingness to endorse varied among disciplines and was negatively correlated with level of religious belief (r = -0.35, P < 0.0001), knowledge of symptom management (r = -0.21, P < 0.0001), and time managing symptoms (r = -0.21, P < 0.0001). On multivariate analysis, the significant predictors were lesser religious belief (P < 0.0001), greater concern about analgesic toxicity (P = 0.001), diminished empathy (P = 0.03), lesser knowledge of symptom management (P < 0.04), and the interaction between religious belief and knowledge of symptom management (P = 0.04). Professionals' attitudes toward assisted suicide are influenced by diverse personal attributes, among which may be competence in symptom management and burnout.

Focus on the nurse: ethical dilemmas with highly symptomatic patients dying at home.

Some serious issues face the inexperienced nurse who has the responsibility for either providing the care or directing the care of symptomatic patients dying at home. Inexperience in such care, and lack of competent medical support, can result in the nurse perceiving "ethical dilemmas" in practices which are, in reality, part of good and ethical palliative care.

Implementing national standards for cancer pain management: program model and evaluation.

The purpose of this quasi-experimental (pre and posttest) study was to test a model pain management program (PMP) to implement the American Pain Society (APS) quality assurance standards for the management of acute and chronic cancer pain using a continuous quality improvement (CQI) approach to improve professionals' knowledge and skills, patient satisfaction, and to identify areas needing improvement. The sample consisted of 1210 nurse responses and 698 interviews of patients with pain during hospitalization at a major urban cancer center. The PMP provided a structure (standards), educational opportunities, and training in CQI methods. Outcome measures included a patient evaluation questionnaire and concerns checklist; nurse knowledge, attitude and barriers questionnaire; and focus groups to identify areas needing improvement. Significant improvements were found in patients' satisfaction, nurses' knowledge and attitude scores, and reductions in nurses' perceptions of barriers. Focus groups revealed the need for improved communication among disciplines about pain and better assessment of patients unable to self-report. The program met its goal of implementing the APS standards, educating nurses, and identifying "system" problems, and improving overall patient satisfaction.

Development and validation of a patient needs assessment tool (PNAT) for oncology clinicians.

The Patient Needs Assessment Tool (PNAT) is an interviewer-rated scale that may be completed through a simple structured interview and screens cancer patients for potential problems in physical and psychosocial functioning. The instrument provides separate scores for physical, psychological, and social status, and can potentially clarify the types of interventions needed to address specific areas of dysfunction. Reliability and validity was tested in two studies that used prescreened patient videotapes and other materials to assess the performance of the PNAT in groups of oncology nurses, physicians, and social workers. The data demonstrate that subscale scores for the physical, psychological, and social dimensions have good inter-rater reliability and internal consistency (intraclass correlation coefficients of 0.71-0.97). Criterion and construct validity was suggested through high correlations of each subscale with the evaluation of expert raters (correlation coefficients of 0.85-0.95) and with scores on validated patient-rated instruments appropriate to the functional area. These analyses suggest that the PNAT is a valid scale for the assessment of a range of functional disturbances in the cancer population.

Age and sex differences in strategies of coping and defense across the life span.

Age and sex differences in the use of coping and defense strategies were examined in life-span sample of 381 individuals. Participants responded to 2 self-report measures assessing mechanisms of coping and defense and measures assessing their level of cognitive complexity. Older adults used a combination of coping and defense strategies indicative of greater impulse control and the tendency to positively appraise conflict situations. Adolescents and younger adults used strategies that were outwardly aggressive and psychologically undifferentiated, indicating lower levels of impulse control and self-awareness. Women used more internalizing defenses than men and used coping strategies that flexibly integrated intra-and interpersonal aspects of conflict situations. Taken together, findings provide evidence for the age- and sex-specific use of strategies of coping and defense, suggesting that men and women may face different developmental tasks in the process toward maturity in adulthood.