Pneumococcal bacteremia in three community teaching hospitals from 1980 to 1989.

STUDY OBJECTIVE: To review the clinical and laboratory findings in a large number of patients with pneumococcal bacteremia in the 1980s and identify risk factors associated with increased mortality. DESIGN: Retrospective review of medical records identified by blood culture logbooks and ICD-9 codes. SETTING: Three community teaching hospitals affiliated with a medical school in northeastern Ohio. PATIENTS: 385 inpatients with pneumococcal bacteremia admitted between Jan 1, 1980 and Dec 31, 1989. MEASUREMENTS: Important clinical and laboratory information was abstracted from patients' medical records, compiled, computerized, and analyzed. MAIN RESULTS: The patients' mean age was 48 years. The overall mortality was 25 percent. The mortality increased with age, reaching 42 percent in patients over 65 years old. For these elderly patients, the mortality was higher (55 percent) for patients admitted from nursing homes than patients from the community (36 percent). Higher mortality was also associated with congestive heart failure (p = 0.001), alcoholism/cirrhosis (p = 0.02), diabetes mellitus (p = 0.05), and malignancy (p = 0.02). A platelet count less than 150,000/mm3, renal dysfunction (serum creatinine > 2 mg/dl), and the number of lobes involved were also associated with mortality. Patients receiving standard therapy (penicillin, ampicillin, erythromycin, or cephalosporins) had lower mortality. Of the previously specified risk factors for mortality, only age, whether standard therapy was administered, the number of lobes involved, and the serum creatinine level proved to be independent risk factors according to logistic regression. CONCLUSIONS: The overall mortality from pneumococcal bacteremia has not decreased during the past 40 years. Risk factors associated with increased mortality were identified. Prevention by immunization with polyvalent pneumococcal polysaccharide vaccine should be practiced more widely.

Daily exercise improved blood pressure homeostasis of rats subjected to surgical stress.

The effect of daily spontaneous running on blood pressure homeostasis (BPH) was evaluated in 19 male and 13 female control rats and 7 male and 13 female daily spontaneous running rats subjected to surgery and subsequent repetitive hemodynamic disturbances. BPH was operationally defined as the ability to maintain mean arterial pressure above 60 mmHg during the experimental protocol. The length of time the rats maintained BPH was compared across males and females and trained and control groups. Significant sex (P = 0.01) and training (P = 0.05) effects were found. Females maintained homeostasis longer than males and trained longer than controls. Sex effects were not due to differences in the body mass. The mechanisms responsible for the higher resistance to deterioration of homeostasis merit further investigation.

Pulmonary vascular protein sieving capability after exposure to high vascular pressures.

We evaluated the ability of the canine in situ left lower lobe (LLL) vasculature to sieve endogenous plasma proteins of various molecular radii (34-124 A) after LLL arterial pressure had been transiently elevated to 23.8 +/- 0.9 (control group, n = 5) or 92.3 +/- 1.4 (SE) Torr (high-pressure group, n = 9) by restricting LLL venous outflow under conditions of constant flow. After LLL flow was returned to natural perfusion, left atrial pressure was elevated in step increments, and LLL lymph and blood samples were collected until filtration-independent lymph-to-plasma protein concentration ratios (CL/CP) were obtained. The osmotic reflection coefficients (sigma d) for total proteins and seven protein fractions (separated by gradient gel electrophoresis) were calculated. The average total protein sigma d of the high-pressure group [0.51 +/- 0.06 (SE)] was significantly lower than that of the control group (0.68 +/- 0.03). Several LLLs of the high-pressure group, however, exhibited normal sigma d's. Protein fraction CL/CP's decreased with increasing molecular radius in both groups, but the CL/CP-molecular radius relationship was displaced upward in the high-pressure group. Pore analysis suggested that the decreases in sigma d could be explained by increases in the fractional flow through a large-pore system.

Using chart reviews to assess residents' performances of components of physical examinations: a pilot study.

PURPOSE: To evaluate chart review as a method of assessing residents' performances of physical examinations in an ambulatory care setting. METHOD: In 1992, nurse authors at the Affiliated Hospitals at Canton of the Northeastern Ohio Universities College of Medicine assessed whether 22 internal medicine residents performed ten components of the physical examination by interviewing patient volunteers immediately after the patients' examinations. A total of 89 patient interviewees were included in the analysis; these patients were all new outpatients who had been scheduled for initial visits to obtain complete histories and physical examinations. Charts for the same patients were then retrospectively reviewed. The residents and faculty were blinded to both the chart reviews and the interviews. Statistical methods used were Pearson correlational analysis and variance-component analysis. RESULTS: The interviews and chart reviews showed 81% agreement in component performance. Completeness of the physical examination (whether measured by chart review or interview) did not correlate with other standard methods of resident evaluation, and completeness did not show a significant association with characteristics of the residents and patients. Two of the 22 residents assessed were identified as having completeness scores so low as to be unsatisfactory. CONCLUSION: That residents were identified as failing to perform examination components suggests that chart reviews, especially when independently verified by patient interviews, may be a useful evaluation tool for identifying inadequate performance of components of the physical examination and may identify the need for remediation.

Modeling heart disease mortality with census tract rates and social class mixtures.

The relationship between social class and 1980 heart disease (HD) mortality in eight urban U.S. counties was examined by regressing age and sex adjusted census tract specific HD rates (N = 1211) on tract social class characteristics. The regression model indicated that lower middle class residents experienced a HD mortality rate 1.9 (95% CI = 1.3, 2.8) times the rate in the upper middle/middle class, while the working poor experienced a HD rate 4.4 (95% CI = 3.5, 5.7) times the rate in the referent class. Similar class effects were seen for both black and nonblack residents. The crude race effect (1.3 with 95% CI = 1.2, 1.4) was explainable by the concentration of blacks in the lower classes. The methods illustrate the ecologic regression of mixtures of mortality rates on mixtures of exposure in the presence of random tract effects which eliminates some of the problems associated with small denominators or zero rates in some tracts.

Geriatric renal function: estimating glomerular filtration in an ambulatory elderly population.

In elderly individuals, serum creatinine may remain normal as glomerular filtration rate (gfr) declines. Therefore, the estimation of glomerular filtration utilizing mathematical models incorporates age as an important variable. In order to adjust drug dosages and diagnose renal disease earlier in the elderly, a variety of such simplified estimates of gfr have been applied. Unfortunately, no estimator is as accurate as the cumbersome gold standards (e.g. inulin or iothalamate clearance) and the reliability of each may vary with the particular clinical setting. The purpose of this study was to critically evaluate three commonly used estimators of gfr-i.e., creatinine clearance (CC), Cockroft-Gault (CG), and 100 over serum creatinine (100/SC)-comparing them to iothalamate clearance (IC) in a group of healthy ambulatory geriatric subjects (n = 41; ages 65-85). IC declined 1 ml/min per year of age in our sample. CC demonstrated a similar decline, a correlation of 0.83 with IC, and moderate error relative to IC of 17% at the mean (standard error [SE] = 12.3). In contrast, 100/SC correlated only 0.56 with IC, demonstrated a large positive bias (41 ml/min), and showed no age-related decline. An age correction to 100/SC similar to that utilized in the CG formula was clearly necessary. Despite the age and weight correction used in the CG formula, we found the estimates from it to be inaccurate (correlation = 0.5; SE = 23.8). A simpler age-corrected formula (Est. IC = 1/2 [100/SC] + 88-age) was derived and proved significantly superior to CG in our ambulatory geriatric sample, but still exhibited enough error (SE = 16.4) to question its clinical utility. It appears that serum creatinine based estimates of gfr in the elderly may not provide accurate results.

Eosinophils in urine revisited.

The finding of eosinophils in the urine has been suggested to be useful in establishing the diagnosis of acute interstitial nephritis (AIN). The diagnostic accuracy of this test has not yet been defined. It is the purpose of this study to define the specificity, sensitivity, and the predictive positive and negative values for the presence of eosinophils in the urine. One hundred forty-eight patients with pyuria were tested for the presence or absence of urinary eosinophils. In this group consecutively admitted to the hospital with WBC in the urine, 4% of patients had urinary eosinophilia of greater than 1 eosinophil per 100 cells. Since none of this group had the diagnosis of AIN, the false positive rate was 4% and the specificity was 96%. In a selected group of patients in which the diagnosis of AIN was suspected by a nephrology consultant, urinary eosinophils were found in 6 of 15 patients with a confirmed diagnosis of AIN but were also found in 10 of 36 patients with another renal diagnosis. The sensitivity for eosinophiluria was 40% and the specificity was 72% with a positive predictive value of only 38%. We conclude that eosinophiluria is not an accurate test for the diagnosis of AIN. The false positive and negative rates are too high to confirm an AIN diagnosis.

Nephrologists' subjective attitudes towards end-of-life issues and the conduct of terminal care.

Decisions which determine the duration and outcome of terminal care should be influenced by patient autonomy. Studies suggest, however, that end-of-life decision-making is more complex than a single principle and that physicians may be responsible for selected aspects of terminal care independent of patient choice. To study how nephrologists' perceptions toward end-of-life issues may affect decision-making, we anonymously surveyed 125 of them. The study employed the straightforward terminology of "hastening death" rather than adopting the ambiguous term "euthanasia" or the narrow term "assisted suicide." Subjective physician profiles demonstrated that nephrologists who are less comfortable with dying patients were significantly less likely to report that they omitted life-prolonging measures (p = 0.02) and more likely to report that they would not initiate measures in order to hasten death even were it legal (p = 0.04). Ninety-eight percent of nephrologists reported omissions in terminal care with patient knowledge and 80% without patient knowledge. In contrast, forty-three percent of the nephrologists said that were it to become legal to initiate measures in order to hasten death, they would "never" do so. The ethical framework utilized for discontinuation of dialysis decisions incorporated medical benefit (cancer as criterion, 48%; multisystem complications, 84%; dementia 79%) and quality of life criteria. Twenty-five percent of nephrologists admitted difficulty with advance directives if the directives clashed with heir beliefs. ESRD end-of-life decision-making in the USA may be altered by the subjective characteristics of nephrologists. In particular, nephrologists' level of discomfort with patient mortality is linked with their reported management of terminal patients.

Prospective comparison of dual-phase technetium-99m-sestamibi scintigraphy and high resolution ultrasonography in the evaluation of abnormal parathyroid glands.

Technetium-99m-sestamibi (MIBI) is a new radionuclide for imaging parathyroid tissue. The purpose of this study was to evaluate parathyroid localization using single radiotracer, dual-phase MIBI scintigraphy and to compare the results to ultrasonography. Twenty-one patients with hyperparathyroidism underwent dual-phase scintigraphy using 25 mCi MIBI and high resolution ultrasonography before parathyroidectomy. Scan results were correlated with size, weight, location, and histopathology of excised parathyroid glands, thyroid abnormalities, and cost. Seventeen patients were female, five had secondary or tertiary hyperparathyroidism, and three had a previous parathyroid exploration. Twenty patients (95%) were cured, 14 with a single and 1 with a double adenoma, and 5 of 6 patients with generalized hyperplasia. There were no false positive MIBI scans and one false positive ultrasound study, despite associated thyroid nodules in 29 per cent of patients. The sensitivity of MIBI and ultrasound in the identification of adenomas was 87 per cent versus 57 per cent (P = 0.046), and the rate of detection of hyperplastic glands was 44 per cent versus 24 per cent (P = 0.19), respectively. There was no correlation between scan results and size, weight, or location of adenomatous glands. The cost of dual-phase MIBI was comparable to that of ultrasound. Dual-phase MIBI is more sensitive than ultrasound in the localization of adenomas and is the preferable modality for preoperative parathyroid localization. Neither MIBI nor ultrasound is effective in localization of hyperplastic glands, underscoring the importance of routine bilateral neck exploration.

Confronting the communication gap between conventional and alternative medicine: a survey of physicians' attitudes.

CONTEXT: An estimated 60 million Americans use some from of complementary and alternative medicine, though approximately 70% do not tell their physicians about this use. Open communication between conventional medical providers and patients in this area is therefore lacking. OBJECTIVE: To explore the dynamics that could potentially contribute to communication breakdown between physicians and patients over the use of alternative therapies. DESIGN: Mail-in, self-administered questionnaire. PARTICIPANTS: 96 practitioners in primary care and medical subspecialties representing the local county medical society, Stark county, Ohio. MAIN OUTCOME MEASURES: Data were obtained on the following: (1) physicians' level of familiarity with 23 different alternative therapies, (2) the question of whether physicians used the therapies themselves, (3) physicians' assessment of the potential benefits and harm of each therapy, and (4) physicians' response to the prospect of their patients using these therapies. RESULTS: Respondents reported the use of myriad alternative therapies. Only 28%, however, referred patients for alternative therapies. The physicians demonstrated clear preferences for specific therapies (i.e., when asked about benefits, familiarity, and reactions to patient use, they responded differently depending on the therapy). Indication that the doctor-patient relationship might be terminated as a result of alternative therapy use was more common among subspecialists than among primary care practitioners. CONCLUSIONS: Overall, physicians demonstrated an open attitude toward alternative therapies. This finding indicates that patients should disclose their use of alternative therapies to their doctors. Increased referral to alternative healthcare providers may require both ongoing peer-reviewed studies of efficacy and increased physician access to information concerning therapies that have undergone definitive study.

End of life issues in ESRD. A study of three decision variables that affect patient attitudes.

The substantial end-stage renal disease (ESRD) mortality rate reflects an older population, worsening comorbidity, and increased cardiovascular disease. Advance directives in ESRD may simplify issues such as cardiopulmonary resuscitation (CPR) and dialysis discontinuation. However, ESRD patients with advance directives may change their mind or allow surrogate leeway for override of end-of-life decisions. Three decision variables (requesting CPR, discontinuation of dialysis with depression, or discontinuation with dementia) were studied in 141 ESRD patients through a 47 item questionnaire. Duration of dialysis (> or = 4 years) (P = 0.002) and prior CPR experience (P = 0.02) increased the probability of refusing CPR by 12 times. The use of surrogates and substituted judgement for dialysis discontinuation with depression was more likely in women (P = 0.0006) and in patients with higher levels of education (P = 0.003). The odds of deciding to discontinue given dementia were three times greater for hemodialysis than peritoneal dialysis patients (P = 0.03). Eighty-three percent of the patients requested that physicians periodically check with them to determine if their advance directives had changed. The authors conclude that advance directives may assist ESRD patients, families, and staff with end-of-life decisions. Three end-of-life decision variables are significantly affected by duration and type of dialysis, previous CPR, gender, and level of education.

Dialysis leg cramps. Efficacy of quinine versus vitamin E.

A controlled randomized double-blind study was done to determine the frequency and severity of leg cramps in 40 patients on dialysis with a history of leg cramps. All patients entered a 2 month placebo washout and were randomized into a 2 month double-dummy phase of quinine 325 mg at bedtime versus vitamin E 400 IU at bedtime. Of the 29 patients completing the study, 16 received quinine and 13 vitamin E. During placebo washout, the vitamin E group had a mean of 10.4 leg cramps per month, and the quinine group had a mean of 10.9. The vitamin E and quinine groups had a 1 month reduction in leg cramps to 3.3 and 3.6, respectively (p < 0.0005 for both groups combined); this was sustained at 2 months. A severity of pain index showed a statistically significant decrease for both groups. The 95% confidence interval for the difference between the number of leg cramps after vitamin E versus quinine treatment (95% confidence interval, -3.8, +3.2) suggests similar efficacy. Quinine and vitamin E were effective treatments for leg cramps in these patients. Considering the potential toxicity of quinine, vitamin E is recommended as the initial treatment of choice for patients on dialysis with leg cramps.

Wharton's jelly in the umbilical cord. A study of its quantitative variations and clinical correlates.

A frozen segment was prepared from each of 398 consecutively collected umbilical cords after stripping them of blood. Three cross-sections were obtained from each cord, and dye imprints were made. Their surface area was measured by placing a transparency with a grid of squares over the imprint and counting the number of squares it occupied. An average of these three cross-sectional areas was taken to estimate the quantity of Wharton's jelly at any point along the umbilical cord. Of the 14 maternal and fetal variables studied, those that were found to be independently related to the estimated quantity of Wharton's jelly in the umbilical cord were male gender (P = < .01), weight of the fetus (P = .05) and maternal prepregnancy weight (P = < .01). These variables, however, explained only 7% of the observed variation in quantity. A further 3.3% was explained by measurement error, leaving 89.7% of the observed variation unexplained.

Autoschizis of human ovarian carcinoma cells: scanning electron and light microscopy of a new cell death induced by sodium ascorbate: menadione treatment.

Human ovarian carcinoma (MDAH 2774) cells were treated with sodium ascorbate (VC), menadione (VK3), or a combination of both in a ratio 100:1 for 1h and then examined with scanning electron microscopy (SEM) and light microscopy (LM). Light microscopy data corroborated SEM observations, which demonstrated that death of VC+VK3-treated tumor cells occurred primarily by autoschizis. This type of cell death is characterized by a decrease in cell size, cytoplasmic self-excisions, and nuclear and nucleolar morphologic degradations without the formation of apoptotic bodies. Ultimately, cell death results from karyorrhexis and karyolysis. This study illustrates that plasma membrane damage (branching filopodia, blisters, blebs) results from VC treatment; cytoskeletal damage and self-morsellation are caused by VC, VK3 and VC+VK, treatments. The VC treatment results in a 23% decrease in cell diameter while VK3-treated cells decrease cell diameter by 66%. After 1h of VC+VK3 treatment, a heterogenous cell population is found. This population can be resolved into one population whose diameters are 23% smaller than those of sham-treated cells, and a second population whose diameters are approximately twice those of sham-treated cells. This second population is indicative of doublet formation in which the cells appear to be dividing (an early stage of autoschizic cell death). One half of the doublet contains the cell nucleus while the other half consists of cytoplasm and membrane only. The enucleate portion of this doublet will then be excised. When the types of cell death are enumerated following VC+VK3 treatment, 43% of the cells die by autoschizis, 3% by apoptosis, and 1.9% by oncosis. These results confirm that autoschizis is the principal form of cell death that results from the in vitro treatment of human ovarian carcinoma cells with the vitamin combination.

Cardiomyocyte aging and hypertrophy: atrial and ventricular changes in normal and myopathic Syrian hamsters.

Cardiac eccentric hypertrophy is associated with complex architectural and metabolic alterations. Atrial and ventricular myocyte diameters in cardiomyopathic (Bio 14.6) and age-matched control (F1b) Syrian hamsters were compared and histopathology was examined by electron microscopy. The mean diameter of ventricular myocyte diameters increased with age in both F1b and Bio 14.6 hamsters. Significantly greater hypertrophy was noted in the Bio 14.6 left ventricle myocytes than the F1b. Histo- and cytopathologic findings included amitotic myocardial divisions and focal myocyte necrosis in Bio hearts. Sarcomere length appeared to be similar across age and strain; however, wider sarcomeres were found in conjunction with wider diameters of myopathic left ventricle myocytes. Moreover, F1b hamsters' atrial myocytes maintained a static diameter, while those of the Bio 14.6 showed hypertrophy even preceding ventricular changes. These findings indicated that the cardiomyopathic heart is characterized by a continued fiber hypertrophy despite cardiac decompensation. Other histopathological findings included amitotic myocardial divisions, focal necrosis and sarcoplasmic widening of Z-lines. In addition, vascular smooth muscles of Bio 14.6 demonstrated vacuolization.

Likelihood ratios for deoxyribonucleic acid (DNA) typing in criminal cases.

The likelihood ratio approach for DNA typing in criminal cases is described. It is shown how this approach uses both the sizes and pattern of discrepancies between the crime scene profile of fragment lengths and the suspect profile for quantifying the strength of the evidence. In contrast to the current match-binning approach, it avoids an initial decision about whether the two profiles match. Likelihood ratios for pairs of profiles that meet the published statistical criteria for a match show a wide range of values including some that indicate the evidence is strongly against identity.

Searching for a pattern: repeat suicide attempts.

1. Although there is a large population of unsuccessful suicide attempts and the same patients are often admitted repeatedly, little investigation has been done to understand this group. 2. Prescription drugs were almost always used in overdose attempts. There was no indication that physicians successfully intervened in preventing abuse of prescribed medication among patients with a history of overdose suicide attempt. 3. Most people choose a method for suicide and repeatedly use the same method (physical versus overdose). The majority of repeat attempts occurred among young people, and alcohol use was especially high when physical methods were used. Identification of these trends could lead to effective intervention.

Akt1 deficiency delays tumor progression, vascular invasion, and distant metastasis in a murine model of thyroid cancer.

Akt activation is common in progressive thyroid cancer. In breast cancer, Akt1 induces primary cancer growth, but is reported to inhibit metastasis in vivo in several model systems. In contrast, clinical and in vitro studies suggest a metastasis-promoting role for Akt1 in thyroid cancer. The goal of this study was to determine the functional role of Akt1 in thyroid cancer growth and metastatic progression in vivo using thyroid hormone receptor (TR) ß(PV/PV) knock-in (PV) mice, which develop metastatic thyroid cancer. We crossed Akt1(-/-) and PV mice and compared tumor development, local progression, metastasis and histology in TRß(PV/PV)/Akt1(+/+) (PVPV-Akt1WT) and TRß(PV/PV)/Akt1(-/-) (PVPV-Akt1KO) mice. Mice were killed at 3, 6, 9, 12 and 15 months; necropsy was performed and serum thyroid stimulating hormone (TSH) was measured. Thyroid hyperplasia occurred in both groups beginning at 3 months; the thyroid size was greater in the PVPV-Akt1WT mice (P<0.001). In comparison with PVPV-Akt1WT mice, thyroid cancer development was delayed in the PVPV-Akt1KO mice (P=0.003) and the degree of tumor invasiveness was reduced. The PVPV-Akt1WT mice displayed pulmonary metastases at 12 and 15 months of age, by contrast PVPV-Akt1KO mice did not develop distant metastases at 15 months of age. Despite continued expression of Akt2 or Akt3, pAkt levels were decreased and there was evidence of reduced Akt effect on p27 in the PVPV-Akt1KO thyroids. TSH levels were similarly elevated in PV mice regardless of Akt1 expression. In conclusion, thyroid cancer development and progression in TR ß(PV/PV) mice are Akt1-dependent, consistent with a tumor progression-promoting role in this murine thyroid cancer model.