Risk factors for bacteriuria with carbapenem-resistant Klebsiella pneumoniae and its impact on mortality: a case-control study.

BACKGROUND: The objective of this study was to evaluate the mortality of and risk factors for bacteriuria due to carbapenem-resistant Klebsiella pneumoniae (CRKp) versus carbapenem-susceptible K. pneumoniae (CSKp) producing extended spectrum ß lactamase (ESBL). METHODS: This was a retrospective case-control study in which 135 case-patients with bacteriuria due to CRKp were compared with 127 control patients with CSKp producing ESBL. In a first step, multivariate Cox regression and Kaplan-Meier survival analysis models were used to determine the difference in mortality between the two groups and risk factors for mortality. In a second step, a univariate analysis was used to identify risk factors for CRKp colonization. RESULTS: There were no significant demographic or clinical differences between the groups. In-hospital mortality in the study and control groups was 29 and 25 %, respectively (non-significant difference). Multivariate analysis revealed that the most important risk factor for mortality in both groups was being bed ridden [hazard ratio 2.2, 95 % confidence interval (CI) 1.23-3.93; P = 0.008]. Patients with CRKp bacteriuria had a longer hospitalization time with a mean ± standard deviation of 28 ± 33 days compared to 22 ± 28 days in the control group (P < 0.05). Several univariate risk factors for acquiring CRKp bacteriuria were identified: antibiotic use [odds ratio (OR) 1.93, 95 % CI 1.18-3.17, p = 0.008], especially colistin (OR 2.04, 95 % CI 1.04-4.02; P = 0.036), presence of a urinary catheter (OR 2.09, 95 % CI 1.2-3.63; P = 0.008), surgery (OR 3.94, 95 % CI 1.85-8.37; P = 0.0002), invasive procedures (OR 3.06, 95 % CI 1.61-5.8; P = 0.0004), and intensive care unit admission (OR 2.49, 95 % CI 1.18-5.37; P = 0.015). CONCLUSION: Bacteriuria caused by CRKp as compared that caused by CSKp was not found to be a risk factor for death.

Calculated versus measured pure tone bone conduction 3 kHz thresholds in sudden sensorineural hearing loss.

OBJECTIVE: To compare the measured bone conduction threshold at 3 kHz with the calculated threshold in newly diagnosed sudden sensorineural hearing loss. METHODS: A retrospective chart review was conducted of pure tone audiograms in confirmed sudden sensorineural hearing loss cases. RESULTS: Of 157 patients with sudden sensorineural hearing loss, 144 had idiopathic hearing loss, 8 had vestibular schwannoma and 5 had Ménière's disease. The r value for the correlation between the two methods of 3 kHz assessment for all patients was 0.887 (p < 0.001). The mean difference between the measured and calculated 3 kHz thresholds was 0.76 ± 7.96 dB, 0.4 ± 8.08 dB and 1.5 ± 1.8 dB in the sudden sensorineural hearing loss, idiopathic and Ménière's disease groups, respectively. The mean difference between the measured and calculated 3 kHz thresholds was significantly greater in the vestibular schwannoma group (6.86 ± 4.38 dB) than in the idiopathic group (p = 0.013). CONCLUSION: The 3 kHz frequency may encompass important audiometric information. A discrepancy between the measured and calculated bone conduction 3 kHz thresholds raises suspicion of an underlying vestibular schwannoma as an aetiology for sudden sensorineural hearing loss, and these thresholds should therefore be measured independently and routinely.

Potentiation of Fas-mediated apoptosis by attenuated production of mitochondria-derived reactive oxygen species.

The role of reactive oxygen species (ROS) production in death receptor-mediated apoptosis is ill-defined. Here, we show that ROS levels play a role in moderating Fas-dependent apoptosis. Treatment of Jurkat T cells with oligomycin (ATP-synthase inhibitor) or (mitochondrial uncoupler) and Fas-activating antibody (CH11) facilitated rapid cell death that was not associated with decreased ATP production or increased DEVDase activity and cytochrome c release. However, a decrease in cellular ROS production was associated with CH11 treatment, and combinations of CH11 with oligomycin or FCCP further inhibited cellular ROS production. Thus, decreased ROS production is correlated with enhanced cell death. A transition from state 3 to state 4 mitochondrial respiration accounted for the attenuated ROS production and membrane potential. Similar observations were demonstrated in isolated rat liver mitochondria. These data show that ROS production is important in receptor-mediated apoptosis, playing a pivotal role in cell survival.

Histomorphometric evaluation of reversible heparin-induced osteoporosis in pregnancy.

Transilial bone biopsy confirmed heparin-induced osteopenia in a 23-year-old postpartum patient. Histomorphometric measurements during the reversible stage of bone disease that followed discontinuation of the heparin sodium therapy revealed signs of recovery; these were superimposed on a loose trabecular structure typical of osteoporosis. The histomorphometric evidence of recovery correlated well with signs of clinical improvement. In the majority of patients, heparin therapy during pregnancy is innocuous; however, discontinuation of treatment is recommended at the earliest signs of osteoporosis.

Islet hormonal regulation of glucose turnover during exercise in type 1 diabetes.

A decline in plasma insulin and an increase in glucagon are known to occur during intense and/or prolonged exercise. However, it is not established whether changes in insulin and glucagon secretion are involved in the precise matching of hepatic glucose production to the enhanced glucose uptake by muscle during brief, low intensity exercise. We studied the effects of 30-min cycle exercise at 40% of maximal aerobic capacity in healthy subjects and C-peptide-deficient subjects with type 1 diabetes (IDDM) using [3-3H]glucose to estimate glucose turnover. Diabetic subjects were studied during continuous iv insulin infusion, which normalized glucose kinetics before experimental perturbations. In control (saline-infused) experiments, endogenous glucose appearance (Ra) increased by 80-90% above baseline to match the increase in glucose disappearance in both normal and IDDM subjects, even though the latter exercised at fixed levels of plasma free insulin, averaging 203 +/- 19 pmol/L. In other experiments, somatostatin was infused, and glucagon (1.0 ng/kg.min) and insulin (at two different rates) were maintained at constant levels. Infusion of insulin in normal subjects at doses sufficient to maintain constant peripheral plasma insulin was associated with no apparent effect on glucose turnover (plasma insulin, 80 +/- 21 pmol/L, compared to 52 +/- 5 pmol/L during saline; P = NS). However, insulin infusion at doses that normalized the portal insulin concentration (approximately 208 pmol/L) together with glucagon replacement inhibited the rise in glucose production in both normal and IDDM subjects. There were similar 45-55% reductions (P less than 0.03) of the increase in Ra seen with exercise in control experiments. When peripheral plasma free insulin (and presumably portal levels as well) were increased by about 20% in this experimental setting in IDDM (278 +/- 43 pmol/L), the suppression of Ra was even more profound, and Ra failed to increase at all with exercise. We conclude that the hormonal regulation of Ra in brief duration exercise in man does not necessitate the decrements in portal venous insulin observed under more intense exercise conditions as long as an exercise-induced glucagon secretory response can occur. Glucagon secretion alone cannot prevent hypoglycemia when portal venous insulin concentrations are increased by minimal amounts, such as in insulin-treated diabetics.

Regulation of counterregulatory hormone secretion in man during exercise and hypoglycemia.

We examined the role of the plasma glucose concentration per se in the secretion of counterregulatory hormones during exercise. Ten men (average age, 24 yr; maximal aerobic capacity, 31.8 mL/kg.min) were studied during two 50-min bicycle exercise periods at either normal glucose [87 +/- 1 (+/- SE) mg/dL (4.8 +/- 0.1 mmol/L)] or low glucose [59 +/- 1 mg/dL (3.3 +/- 0.1 mmol/L)]. The plasma glucose targets were achieved by exogenous insulin and variable glucose infusions. These results were compared to studies in which saline was infused. Exercise at normal glucose was associated with significant increments in plasma epinephrine (maximum 3- to 5-fold above baseline) and norepinephrine (2-fold), comparable to those that occurred during saline administration. Plasma GH increased only at the most intense exercise level, while plasma cortisol and glucagon did not increase significantly. In low glucose-exercise studies, the increase in plasma epinephrine during exercise was significantly greater than that at normal glucose (P less than 0.01), although proportional to basal preexercise levels (r = 0.73; P less than 0.001). Plasma glucagon increased almost 100%, and plasma cortisol and GH increased by 150% and 400%, respectively. Compared to the effect of the same degree of hypoglycemia in the absence of exercise, only plasma epinephrine (P = 0.002) and norepinephrine (P less than 0.001) displayed effects independent of hypoglycemia during exercise. When low glucose was reversed to normal at the midpoint of exercise, plasma epinephrine and glucagon returned to the levels obtained for the same duration of exercise at normal glucose, while norepinephrine, GH, and cortisol were only partially responsive to the rise in plasma glucose. These data suggest that 1) moderate exercise is a stimulus for a sympathoadrenal and GH response, but not a peripheral glucagon response; 2) during exercise and hypoglycemia, plasma epinephrine and norepinephrine are enhanced, while the glucagon response is entirely glucose dependent; and 3) the epinephrine response to hypoglycemia can be dissociated from that to exercise, suggesting differing control mechanisms. We conclude that the activation of counterregulatory hormones during exercise is regulated by glucose-independent mechanisms, although these responses may be augmented by concurrent hypoglycemia.

Hypoglycemia in hospitalized nondiabetic older patients.

OBJECTIVES: To analyze the clinical characteristics, associated risk factors, and outcome of hypoglycemia in nondiabetic hospitalized older patients. DESIGN: A retrospective case control study. PARTICIPANTS: Sixty patients, aged 65 years and older, in the acute medical and geriatric wards who developed hypoglycemia. A control group was composed of 83 older patients, sex and age matched, in orthopedic and surgery wards who were undergoing corrective surgery for hip fracture or hernioplasty. MEASUREMENTS: For all patients, data for the following variables were abstracted from the charts: age, sex, degree of hypoglycemia, clinical presentation of hypoglycemia, number and duration of hypoglycemia episodes, nutritional state, and blood chemistry analysis. Risk factors were defined as nutritional state, heart failure, renal or liver disease, malignancy, and infection or sepsis. RESULTS: Mean blood glucose in hypoglycemic cases was 38.9 +/- 7 mg/dL. Symptoms and signs of hypoglycemia were noted in only 38.4% (23/60) of patients. All identified risk factors except cachexia were found significantly more frequently in the hypoglycemic patients than in the control group. Mean total number of risk factors was greater in the hypoglycemic group than in the control group, 2.97 +/- 1.1 versus 1.64 +/- .8, respectively (P < .001). In a multivariant logistic model, low plasma albumin level, liver disease, malignancy, and congestive heart failure were significant predictors of hypoglycemia. In-hospital mortality rate was higher among the hypoglycemic patients, 48% versus 18.1% (P < .001), and was independent of the degree of hypoglycemia or the number of hypoglycemic episodes. Mortality was correlated significantly with the number of risk factors (3.4 +/- 1.1 vs 2.5 +/- 1.1; P = .006). Hypoglycemia remained a significant predictor of mortality (OR = 3.67; 95% CI, 1.2-11.2) even after the adjustment for other risk factors. CONCLUSIONS: Hypoglycemic episodes occur even among nondiabetic hospitalized older patients. Symptoms and signs of hypoglycemia were noted in only two-fifths of the patients. Albumin less than 3.0 g%, liver disease, renal insufficiency, malignancy, congestive heart failure, and sepsis were statistically significant predictors of developing hypoglycemia. The overall mortality rate was significantly higher among the hypoglycemic patients and was independent of hypoglycemia levels. Mean total number of risk factors was significantly higher among those who died compared with hypoglycemic patients who survived. Based on the present study, the estimated odds of mortality in an older patient with hypoglycemia were 3.67 times higher than in those without hypoglycemia.

Increased prolactin response to thyrotropin-releasing hormone in primary ovarian failure.

To investigate prolactin (PRL) and thyrotropin-stimulating hormone (TSH) secretion in ovarian failure, 14 women with primary ovarian failure were challenged with luteinizing hormone-releasing hormone (LHRH) (100 micrograms) and thyrotropin-releasing hormone (TRH) (200 micrograms) given intravenously at 30-minute intervals. Responses were compared with those of 13 healthy female controls. In the patient group, basal follicle-stimulating hormone (FSH), LH, and peak gonadotropin responses to LHRH were higher and basal estrone and estradiol levels were lower than in the controls (P less than .001). Mean basal PRL levels were similar in the 2 groups. However, the mean peak and integrated PRL responses in the patients were greater than in the controls (P less than .05). Ten patients had a markedly exaggerated PRL response to TRH. The mean basal TSH levels and the peak TSH response to TRH were similar to those of the controls. Estrogens are known to stimulate PRL secretion. These subjects had increased PRL responses with low circulating estrogens. The mechanism underlying the findings is not known, but could be related to increased aromatization of androgens to estrogens in the hypothalamus. Alternatively, other factors could be responsible for the exaggerated PRL responses to TRH noted in these patients with primary ovarian failure.

Single intravenous bolus of dexamethasone for the differential diagnosis of Cushing's syndrome.

We developed a 24 hour intravenous dexamethasone suppression test for the differential diagnosis of Cushing's syndrome. Basal ACTH and cortisol levels were measured at 8 and 9 AM; a bolus of 8 mg dexamethasone phosphate (in children 5 mg/m2) was administered intravenously, and cortisol levels were measured hourly until 3 PM, then every 2 hours until midnight, and the next morning at 8 and 9 AM. We studied 13 patients with an ACTH-secreting pituitary adenoma, four with an autonomous adrenal adenoma, a 10 year-old girl with primary adrenocortical nodular dysplasia, one male with an ACTH-secreting medullary carcinoma of the thyroid, and one male with an ACTH-secreting non-small cell carcinoma of the lung, and compared their results to those obtained in 8 lean and 12 obese normal individuals (controls). The clinical diagnosis was first ascertained by the response to the oral administration of dexamethasone in low and high doses (standard Liddle test), then by the intravenous dexamethasone suppression test, and finally confirmed surgically. Although both controls and patients with an ACTH-secreting pituitary adenoma significantly suppressed their cortisol levels within hours after the injection (50% reduction of basal value at 2 hours, and 75% at 4 hours, p < 0.0001), levels remained suppressed the next morning only in the controls, while in the patients they returned to basal values. No suppression was observed in any of the patients with an adrenal adenoma and the child with primary adrenocortical nodular dysplasia (whose ACTH levels were low), or in the patients with ectopic ACTH secretion tumors (whose ACTH levels were high).(ABSTRACT TRUNCATED AT 250 WORDS)

[Pyogenic cervical osteomyelitis following pneumonia].

A 65-year-old man was admitted because of severe cervical pain radiating to both shoulders and bouts of fever, which followed pneumonia. Bone scan showed increased focal uptake in C6-7, while computerized tomography showed destruction of the 7th intervertebral disk, with bone sequesters and soft tissue swelling. Fine needle aspiration drew purulent material with gram-positive bacteria on direct staining. Culture grew Staphylococcus aureus, coagulase positive. Treatment with IV cloxacillin for 3 weeks, followed by oral treatment for another 3, resulted in complete remission.

A trichromatic test for spheric and astigmatic refraction.

An improved chromatic rotatable refraction test for simultaneous spheric and astigmatic refraction is described. Its new features are interposition of a bright yellow stripe between the conventional red and green fields and a pair of parallel test lines, which traverse vertically all colored fields. Thereby astigmatic errors become easily visible.