Embolization of a ruptured aneurysm in classic polyarteritis nodosa presenting as perirenal hematoma

A 26-year-old man was admitted with abdominal pain, anemia, and hypertension. Ultrasonography and computed tomography revealed a perirenal hematoma. Soon after admission, the patient went into shock, and emergency angiography was performed. Two active bleeding sites were found in the left kidney and were successfully embolized. Also, multiple aneurysms, consistent with the diagnosis of classic polyarteritis nodosa, were seen. After treatment was initiated, the patient recovered fully. When a spontaneous perirenal hematoma is a presenting symptom of classic polyarteritis nodosa, a delay in making the right diagnosis is likely to occur. Angiography not only may provide a quick diagnosis, but it can also be used to perform therapeutic embolization. In patients with classic polyarteritis nodosa and hemorrhage from a ruptured aneurysm, angiography may be a therapeutic alternative to surgery.     

Evidence-based dental care--a concept review

PURPOSE: Our purpose was to examine the benefits of assisted hatching in our program and to determine whether the procedure increases the implantation of nonviable embryos or monozygotic twinning. METHODS: Consecutive in vitro fertilization cycles using assisted hatching were compared with historical controls. The impact of assisted hatching was analyzed according to the woman's age. Outcome measures were clinical pregnancy, implantation rate, delivery rate, multiple pregnancy, spontaneous abortion, and incidence of monozygotic twins. RESULTS: The implantation rate was increased in women aged 35-39 and markedly increased in women aged 40-42. There was no change in spontaneous abortions and no increase in monozygotic twins. CONCLUSIONS: Assisted hatching is a safe and highly effective adjunct to in vitro fertilization for women aged 35-42 and did not increase spontaneous abortion or monozygotic twinning.     

A randomized controlled trial of filgrastim as an adjunct to antibiotics for treatment of hospitalized patients with community-acquired pneumonia. CAP Study Group

OBJECTIVE: The aims of the study were to follow prospectively the intrasubject progression of idiopathic PD in a cohort of patients using levodopa kinetic-dynamic modeling and to assess the relation between the rate of progression of the disease and patients' different clinical characteristics. METHODS: Thirty-four patients (Hoehn and Yahr stages 1 to 3) enrolled in the longitudinal follow-up. Each patient was examined at 1-year intervals over a median 4 years by a standardized oral levodopa test. The primary measure outcome was the computed half-life of levodopa in the "effect compartment" (t1/2eq), a proposed indicator of nigrostriatal dopaminergic functionality and integrity. RESULTS: Values of levodopa t1/2eq correlated negatively with severity of symptoms (r = -0.652, p < 0.0001) and decreased over the years together with a worsening of patients' clinical stage (p < 0.001). The rate of reduction in drug t1/2eq was more rapid in patients at the earlier stages of the disease compared with the more advanced ones, falling from a median annual reduction of 37 minutes in patients at initial Hoehn and Yahr stage 1 to 6.5 minutes in stage 3 patients (p < 0.001). Patients without tremor at onset, otherwise comparable to patients with tremor for baseline values of levodopa t1/2eq, disease severity, duration, and daily dose of levodopa, tended to show a higher rate of reduction in levodopa t1/2eq than patients with tremor. Overall, patients' annual reduction in levodopa t1/2eq over baseline values averaged 17+/-9%. CONCLUSIONS: These results are in keeping with PET findings on the objective assessment of idiopathic parkinsonism evolution, and they support the suggestion that levodopa pharmacodynamic modeling may offer a practical clinical tool to assess indirectly the functional integrity of the nigrostriatal dopaminergic system over time in parkinsonian patients.     

Urine osmolality and conductivity as indices of hydration status in athletes in the heat

PURPOSE: The purpose of this study was to determine a quick and easy method for assessment of day-to-day hydration status in athletes in the heat. METHODS: Measurement of the osmolality of the first urine sample of the day collected after wakening but before breakfast established a standardized collection procedure to allow day-to-day comparisons of individuals. RESULTS: Laboratory measurements established that a difference in osmolality is found when individuals are dehydrated by a moderate extent in comparison with an euhydrated situation: the osmolality of the first morning urine sample of control subjects (N = 11) averaged over 5 d was 675 (+/- 232) mosmol.kg-1 (mean +/- SD). For subjects who were hypohydrated by exercise followed by fluid restriction, morning urine osmolality was 924 (+/- 99) mosmol.kg-1 (P < 0.001, N = 11, averaged over 7 d). Field measurements from 29 athletes undertaking warm weather training indicated that the athletes could, with appropriate feedback, maintain a satisfactory hydration status. Athletes in weight category sports tended to record a higher morning urine osmolality, reflecting their attempts to dehydrate: recorded values were 627 (+/- 186) mosmol.kg-1 (nonweight category sports, N = 8), 775 (+/- 263) mosmol.kg-1 (boxers, N = 15) and 777 (+/- 254) mosmol.kg-1 (wrestlers, N = 6). Results obtained with a hand-held portable conductivity were compared with those from measured osmolality. CONCLUSIONS: The findings suggest that such an instrument could provide athletes with reliable information as to their hydration status from measurement of the first morning urine of the day and therefore provide a quick and easy method for achieving an approximation of hydration status from day-to-day.     

Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? An observational study of 80 cases

The results of recent investigations of the analgesic and the nonanalgesic effects of opioid glucuronides are relevant to the research on drug abuse in forensic toxicology. As has been shown for heroin, knowledge of the state of distribution and elimination of active and inactive metabolites and glucuronides offers new possibilities in forensic interpretation of analytic results. Because of similar metabolic degradation, calculation of the time-dependent ratio of the concentration of morphine and its glucuronide metabolites in blood or serum allows a rough estimation of increased dosage and of time elapsed since the last application. Drug effects can be examined with respect to individual case histories, including overdose and survival time if the patient died. However, different methods of administration and the strong influence of different volumes or compartments of distribution of parent compounds and metabolites on concentrations in human body tissues require careful use of glucuronide concentration data. In Germany, dihydrocodeine (DHC) is prescribed as a heroin substitute, and relative overdoses are needed to be effective. DHC metabolism was studied in three patients who died from overdoses. All metabolites (dihydrocodeine-6-glucuronide [DHC6], nor-DHC [NDHC], dihydromorphine [DHM], nor-DHM [NDHM], and DHM-3- and 6-glucuronide [DHM3G, DHM6G]) were determined using HPLC and fluorescence detection. Concentrations of DHM (0.16 mg/L to 0.22 mg/L serum) were found. The DHM glucuronide ratios were similar to those of morphine. Receptor binding studies showed that the binding affinity of DHM to porcine mu-receptor was higher than that of morphine, and DHM6G's binding affinity was as high as that of morphine-6-glucuronide (M6G). Metabolites may play an important role in the effectiveness of DHC in substitution and toxicity. Because of enzyme polymorphism, the formation of DHC poses a risk for proper dosage in patients who are either poor or extensive metabolizers. The distribution of opioid glucuronides in cerebral spinal fluid in relation to transcellular transport in central nervous tissue is discussed with respect to the receptor binding of opiates and drug effect.     

Phenotype and genotype of advanced premalignant head and neck lesions after chemopreventive therapy

BACKGROUND: The goal of chemoprevention is to reduce the risk of cancer development by reversing or blocking the tumorigenic process through the use of pharmacologic or natural agents. To determine the potential role of genetic alterations in assessing cancer risk and in evaluating the efficacy of chemopreventive agents, we studied 22 patients with advanced premalignant lesions of the head and neck who were part of a prospective cancer prevention trial that is investigating a regimen of 13-cis-retinoic acid, interferon alfa, and alpha-tocopherol administered for 12 months or until disease progression. METHODS: We used polymerase chain reaction analysis of microsatellite DNA sequences in cells from precancerous lesions to determine the frequencies of genetic alterations--namely, loss of heterozygosity (LOH) and microsatellite instability--at chromosomal loci that are commonly deleted in head and neck cancer. RESULTS: Prior to treatment, 17 (81%) of 21, eight (44%) of 18, and eight (42%) of 19 patients who were informative (i.e., heterozygous) at chromosomes 9p21, 3p14, and 17p13, respectively, exhibited LOH in at least one of their lesion biopsy specimens. Among nine patients who exhibited LOH at chromosome 9p21 in pretreatment biopsy specimens and who had completed at least 5 months of therapy, the genetic loss persisted in eight--including three of the four patients who exhibited complete histologic responses (i.e., no evidence of dysplasia in their biopsy specimens). IMPLICATION: Our data suggest that clinical and histologic assessments of the response to chemopreventive agents may be insufficient to determine their efficacy and that critical genetic alterations could be used as independent biomarkers to augment the ability to evaluate the efficacy of such agents.     

Traumatic aortic rupture: diagnosis and management

BACKGROUND: Traumatic aortic rupture is a relatively uncommon lesion that presents the cardiothoracic surgeon with unique challenges in diagnosis and management. To address controversial aspects of this disease, we reviewed our experience. METHODS: The study was performed by retrospective chart review. RESULTS: Forty-two patients with traumatic thoracic aortic ruptures were managed between January 1988 and June 1997. Nine arrived without vital signs and died in the emergency department. Admission chest radiographs were normal in 3 patients (12%) and caused significant delays in diagnosis. Four of 30 patients admitted with vital signs had rupture before thoracotomy and died. Twenty-six underwent aortic repair. In 1 patient repair was performed with simple aortic cross-clamping, whereas a second was managed with a Gott shunt. The remaining 24 patients had repair with partial left heart bypass. In 1 patient hypothermic circulatory arrest was required. Two patients (7.7%) died. There were no cases of new postoperative paraplegia in the bypass group. There was no morbidity directly attributable to the administration of heparin for cardiopulmonary bypass. CONCLUSIONS: In a discrete group of patients with traumatic rupture of the aorta, the rupture will become complete during the first few hours of hospital admission; aggressive medical treatment with beta-blockade and vasodilators in the interval before the operation is an essential aspect of management. Active distal circulatory support with partial left-heart bypass provides the optimal means of preventing spinal cord ischemia during repair of acute traumatic aortic rupture.     

Processing of human intestinal prolactase to an intermediate form by furin or by a furin-like proprotein convertase

Human lactase-phlorizin hydrolase (human-LPH) is synthesized as a large precursor (prepro-LPH), then cleaved to a pro-LPH of 220 kDa which is further cut to a "mature-like LPH" of a size close to that of mature LPH, i.e. about 150 kDa (in the processing of rabbit pro-LPH the intermediate has a mass of approximately 180 kDa). By coexpression of human prepro-LPH with furin in COS-7 cells we show that furin generates a mature-like LPH. Radioactive amino acid sequence analysis reveals that furin recognizes the motif R-T-P-R832, a protein convertase consensus, to generate a NH2 terminus located 36 amino acids upstream of the NH2 terminal found in vivo at Ala869. This intermediate is ultimately cleaved to the mature LPH form by other proteases including the pancreatic ones. These data demonstrate that human pro-LPH, like the rabbit enzyme, is processed to the mature enzyme by furin or furin-like enzymes through at least an intermediate form that has, however, an apparent mass close to that of the mature enzyme.     

Inhibition of voltage-dependent sodium channels by the anticonvulsant gamma-aminobutyric acid type A receptor modulator, 3-benzyl-3-ethyl-2-piperidinone

3-Benzyl-3-ethyl-2-piperidinone (3-BEP) belongs to a family of compounds that includes alpha- substituted gamma-butyrolactones, gamma-thiobutyrolactones, 2-pyrrolidinones and hexahydro-2H-azepin-2-ones. Many of these drugs exhibit potent in vivo anticonvulsant activity in mice. Previous electrophysiological studies demonstrated that they potentiate gamma-aminobutyric acid- (GABA) mediated chloride currents. This GABAA receptor modulation was thought to be the main mechanism of anticonvulsant activity. We report that 3-BEP also modulates sodium channels. It decreased sodium currents in cultured rat hippocampal neurons in a voltage- and concentration-dependent manner. The drug's apparent affinity increased as neurons were depolarized. At a holding potential of -60 mV, the apparent IC50 was 487 microM. This concentration is comparable to its EC50 for GABAA modulation (575 microM). Current blockade occurred over all activation voltages tested. The steady state inactivation curve was shifted by 600 microM 3-BEP from V50 = -65.3 mV to -72.0 mV, and recovery from inactivation was slowed from tau = 4.9 to 12.8 msec. Sodium current inhibition was not observed for three related compounds, suggesting a degree of chemical specificity for this activity. We conclude that in addition to its known effects on GABAA receptors, 3-BEP modulates sodium channels. Therefore this compound may prevent seizures by both enhancing inhibition and diminishing neuronal excitability.     

Ecto-nucleotidases terminate purinergic signalling in the cochlear endolymphatic compartment

There is strong evidence for a purinergic signalling system in the inner ear which regulates auditory sensitivity. This study describes the terminating mechanism for purinergic signalling in the cochlear endolymphatic compartment via ecto-nucleotidases. Exogenous ATP was introduced into the scala media (SM) of the isolated, perfused guinea-pig cochlea, and the effluent was assayed for the adenine nucleotide metabolites by reverse-phase HPLC. Tissue viability was confirmed by fluorescence imaging of cochlear tissues. Extracellular ATP degradation to adenosine was Ca2+/Mg2+ dependent, and was not affected by inhibitors of intracellular ATPases and non-specific alkaline phosphatase. High azide concentration (5 mM) and suramin produced an inhibitory effect on ATP hydrolysis, consistent with inhibition of E-type ATPase activity. The Vmax of ATP hydrolysis (2564 mumol min-1 SM-1) was indicative of high ecto-ATPase activity. Our results support the role of ecto-nucleotidases as a principal mechanism for termination of purinergic signalling within SM, a compartment of the cochlea showing considerable P2X receptor expression.