Fundamental relationships between blood pressure and cerebral blood flow in humans.

Cerebral blood flow responses to transient blood pressure challenges are frequently attributed to cerebral autoregulation (CA), yet accumulating evidence indicates vascular properties like compliance are also influential. We hypothesized that middle cerebral blood velocity (MCAv) dynamics during or following a transient blood pressure perturbation can be accurately explained by the windkessel mechanism. Eighteen volunteers underwent blood pressure manipulations, including bilateral thigh-cuff deflation and sit-to-stand maneuvers under normocapnic and hypercapnic (5% CO2) conditions. Pressure-flow recordings were analyzed using a windkessel analysis approach that partitions the frequency-dependent resistance and compliance contributions to MCAv dynamics. The windkessel was typically able to explain more than 50% of the MCAv variance, as indicated by R(2) values for both the flow recovery and postrecovery phase. The most consistent predictors of MCAv dynamics under the control condition were the windkessel capacitive gain and high-frequency resistive gain. However, there were significant interindividual variations in the composition of windkessel predictors. Hypercapnia consistently reduced the capacitive gain and enhanced the low-frequency (0.04-0.20 Hz) resistive gain for both thigh-cuff deflation and sit-to-stand trials. These findings indicate that 1) MCAv dynamics during acute transient hypotension challenges are dominated by cerebrovascular windkessel properties independent of CA; 2) there is significant heterogeneity in windkessel properties between individuals; and 3) hemodynamic effects of hypercapnia during transient blood pressure challenges primarily reflect changes in windkessel properties rather than pure CA impairment.

Signal quality measures for unsupervised blood pressure measurement.

Accurate systolic and diastolic pressure estimation, using automated blood pressure measurement, is difficult to achieve when the transduced signals are contaminated with noise or interference, such as movement artifact. This study presents an algorithm for automated signal quality assessment in blood pressure measurement by determining the feasibility of accurately detecting systolic and diastolic pressures when corrupted with various levels of movement artifact. The performance of the proposed algorithm is compared to a manually annotated reference scoring (RS). Based on visual representations and audible playback of Korotkoff sounds, the creation of the RS involved two experts identifying sections of the recorded sounds and annotating sections of noise contamination. The experts determined the systolic and diastolic pressure in 100 recorded Korotkoff sound recordings, using a simultaneous electrocardiograph as a reference signal. The recorded Korotkoff sounds were acquired from 25 healthy subjects (16 men and 9 women) with a total of four measurements per subject. Two of these measurements contained purposely induced noise artifact caused by subject movement. Morphological changes in the cuff pressure signal and the width of the Korotkoff pulse were extracted features which were believed to be correlated with the noise presence in the recorded Korotkoff sounds. Verification of reliable Korotkoff pulses was also performed using extracted features from the oscillometric waveform as recorded from the inflatable cuff. The time between an identified noise section and a verified Korotkoff pulse was the key feature used to determine the validity of possible systolic and diastolic pressures in noise contaminated Korotkoff sounds. The performance of the algorithm was assessed based on the ability to: verify if a signal was contaminated with any noise; the accuracy, sensitivity and specificity of this noise classification, and the systolic and diastolic pressure differences between the result obtained from the algorithm and the RS. 90% of the actual noise contaminated signals were correctly identified, and a sample-wise accuracy, sensitivity and specificity of 97.0%, 80.61% and 98.16%, respectively, were obtained from 100 pooled signals. The mean systolic and diastolic differences were 0.37 ± 3.31 and 3.10 ± 5.46 mmHg, respectively, when the artifact detection algorithm was utilized, with the algorithm correctly determined if the signal was clean enough to attempt an estimation of systolic or diastolic pressures in 93% of blood pressure measurements.

Follicular thyroid carcinoma presenting as axial skeletal metastases.

INTRODUCTION: Common modes of presentation of follicular thyroid carcinoma include a solitary thyroid nodule and cervical lymphadenopathy. We report four patients who presented with axial skeletal metastases rather than the usual neck lumps. METHODS: A review of a database of 389 cases of thyroid cancer, managed by our department from 1990 to 2003, was perfomed. Based on each patient's presenting clinical feature, patients for the case series were selected. RESULTS: Four of the 389 patients presented with axial skeletal metastases - three were in the scalp while the fourth was in the sacral region. The histology of all four cases was that of follicular thyroid carcinoma. Despite widespread metastases at presentation, the overall survival rates of these patients remained relatively good. CONCLUSION: Patients presenting with lesions suspicious of secondary malignancy in the axial skeleton should be clinically evaluated for thyroid cancer. This is especially important if the patient belongs to a high risk age group and has highly vascular lesions.

Glomerular pathology of allograft kidneys in Hong Kong.

AIMS: Our goal was to define the spectrum of glomerular diseases in allograft kidneys and to correlate them with clinical parameters. METHODS: Eight hundred ninety-one renal graft biopsies and 43 graft nephrectomies from 1980 to 2004 were obtained from 442 allografts transplanted to 425 patients. RESULTS: Glomerular diseases were diagnosed in 33% of kidney grafts. Indications for biopsy were baseline assessment (23 biopsies, 2.5%); renal dysfunction (790 biopsies, 88.7%); proteinuria (154 biopsies, 17.3%); hematuria (11 biopsies, 1.2%); and study protocol (four biopsies, 0.4%). The median time to take a biopsy was less than 8 months posttransplant. The mean time posttransplant when the biopsy diagnosis was made was 70 months for IgA nephropathy (IgAN); 66 months for transplant glomerulopathy (TG); 65 months for focal segmental glomerulosclerosis (FSG); 55 months for mesangiocapillary glomerulonephritis (MCGN); 45 months for membranous glomerulonephritis (GN); 49 months for mesangial proliferative GN; and 101 months for diabetic nephropathy. Recurrent glomerular disease was documented in 31 (7.0%) grafts. Specific glomerular diseases were diagnosed by biopsies in 106 (89.1%) of 119 proteinuric allografts. CONCLUSIONS: Glomerulopathy was common in allografted kidneys. IgAN, TG, FSG, mesangial proliferative GN, and membranous GN were the majority. A higher proportion of grafts from donors related to the recipients than from unrelated donors showed IgAN (P < .05), suggesting that genetic factors might play a role in the pathogenesis of IgAN. Recurrence of glomerulopathy underlying ESRD was frequent for IgAN, FSG, and MCGN, but this was rarely seen in membranous GN.

Physiological aspects of vetiver grass for rehabilitation in abandoned metalliferous mine wastes.

Physiological aspects of why vetiver grass (Vetiveria zizanioides L.) can be tolerant to heavy metals and be used as an alternative method for rehabilitation of abandoned metalliferous mine wastelands have been investigated. The results showed that high proportions of lead and zinc (Pb/Zn) tailing greatly inhibited the leaf growth, dry matter accumulation, and photosynthesis of leaves, but stimulated the accumulation of proline and abscisic acid (ABA), and enhanced the activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT), implying that different mechanisms to detoxify active oxygen species (AOS) existed in different parts of plants. Physiological responses to heavy metal treatments differed greatly between roots and shoots. Nitrogen fertilizer application could greatly alleviate the adverse effects of high proportions of Pb/Zn tailing on vetiver grass growth.

Unexplained recurrent pericardial effusion: a lethal warning?

A case of a 37 year old man with cardiac angiosarcoma causing recurrent pericardial effusion, who eventually died of cardiac rupture, is presented. The diagnosis was not established until the postmortem examination despite echocardiography, pericardiocentesis, and pericardial biopsy investigations. There is neither a specific manifestation that enables early recognition nor well proven effective treatment against this disease. Accordingly, the prognosis of cardiac angiosarcoma remains grave. A high index of suspicion is recommended in patients who present with unexplained pericardial effusion.

Primary actinomycosis mimicking urachal carcinoma.

We report a case of urachal actinomycosis that presented with a progressively enlarging infraumbilical mass associated with umbilical discharge. Computed tomography revealed an extraperitoneal mass involving the dome of the bladder. The possible diagnosis included a malignant urachal neoplasm or chronic inflammatory mass. Partial cystectomy and excision of the mass was performed. The pathologic examination revealed actinomycosis. The patient was treated with a 6-month course of antibiotics. No recurrence was noted 1 year postoperatively.

Esophageal blue nevus: an isolated endoscopic finding.

BACKGROUND: The occurrence of blue nevus has seldom been reported in extracutaneous sites and with no record in the esophagus. CASE REPORT: A blue nevus was reported in the esophagus of a 58-year-old Chinese woman. On endoscopic examination, the lesion presented as linear patches of bluish pigmentation in the esophagus. The patient was free of symptoms 3 years after the endoscopic examination. CONCLUSIONS: We believe this represents the first reported case of blue nevus in the esophagus. The clinicopathologic features, differential diagnoses, and the nature of the lesion are discussed, along with a review of the literature.

Case report: follicular adenoma in a thyroglossal duct remnant arising entirely within the hyoid bone.

INTRODUCTION: We describe here the first reported case of a follicular adenoma arising from a thyroglossal duct remnant within the hyoid bone in Singapore. CLINICAL PICTURE: A 32-year-old woman presented with an asymptomatic lump in the anterior midline of her neck of three months' duration. CT scan showed an expansile lesion localised to the medulla of the body of the hyoid. TREATMENT: A well-defined intrahyoidal mass was found at surgery. Histology revealed a follicular adenoma arising from maldescended thyroid tissue within the hyoid bone. OUTCOME: Recovery was uneventful. CONCLUSION: It is important to consider thyroglossal duct carcinomas as a differential diagnosis when evaluating anterior neck lumps.

Sudden death from massive pulmonary tumor embolism due to hepatocellular carcinoma.

Massive pulmonary embolism in cancer patients can be due to detached thrombi or tumor. Pulmonary tumor embolism is often undiagnosed antemortem. We report a 52-year-old Chinese man admitted for management of hepatocellular carcinoma (HCC). Computerized tomography showed tumor involvement of hepatic vein and inferior vena cava. He died suddenly on the day of admission. At autopsy the main pulmonary arteries of both lungs were blocked by large tumor emboli, the immediate cause of death. Although rapid death in patients with HCC is usually caused by intraperitoneal hemorrhage from spontaneous rupture of tumor, massive pulmonary tumor embolism should also be considered in these patients, especially when antemortem evidence of hepatic vein and/or inferior vena cava invasion is present.

The effect of supplementation with isoflavones on plasma lipids and oxidisability of low density lipoprotein in premenopausal women.

Results of recent clinical studies have lead to the hypothesis that isoflavones are cardioprotective. The aims of this trial were to determine the effect of supplementation with isoflavonoid phytoestrogens on plasma cholesterol concentrations and its distribution among lipoproteins and whether supplementation with isoflavones influences oxidisability of low density lipoprotein (LDL) ex vivo. Fourteen healthy premenopausal women participated in a randomised cross-over trial lasting four menstrual cycles (approximately 4 months). The subjects were asked to consume 86 mg of isoflavones daily for the duration of two menstrual cycles followed by placebo for an equivalent period, or vice versa. Venous blood samples were collected initially and at the end of the second and fourth menstrual cycles for the determination of plasma lipid concentrations and the resistance of LDL to copper-induced oxidation ex vivo. Accustomed dietary intake of isoflavones and lignans during the placebo period were 6.87+/-3.0 and 1.80+/-0.22 mg/day (mean+/-S.E.M.), respectively, and these did not change during the supplementation period. The intake of other dietary components remained constant during the trial. Supplementation resulted in a 5-fold increase in urinary isoflavone excretion (12.2+/-14.2 versus 70.1+/-10.3 micromol/24 h, placebo and isoflavone periods, respectively, P=0.0001). No changes in the oxidisability of LDL (lag time of 32.9+/-3.1 versus 30.4+/-2.9 min) or the plasma concentrations of total cholesterol (4.03+/-0.21 versus 4.11+/-0.18 mmol/l) or triacylglycerol (0.67+/-0.04 versus 0.73+/-0.06 mmol/l) were observed following supplementation. However a significant period effect (P=0.024) was observed and a trend towards a carryover effect (P=0.086) was noted for the concentration of HDL(3) cholesterol. Further studies are required to clarify the potential effect of isoflavones on HDL metabolism and the interaction with plasma steroid hormones during the menstrual cycle.

Somatic mutations in the BRCA1 gene in Chinese sporadic breast and ovarian cancer.

Inherited mutations in the BRCA1 gene confer increased susceptibility to breast and ovarian cancer. Its role in sporadic carcinogenesis is not well defined. Somatic mutations in breast cancers have not been reported and to date there are only three reports of somatic mutations in sporadic ovarian cancers. To investigate the contribution of BRCA1 mutations to sporadic breast and ovarian cancer in the Chinese population, we analysed 62 samples from Chinese women using the protein truncation test. There were 40 cases of breast cancer under age 50 and 22 cases of ovarian cancer, all unselected for family history. There was no age selection for the ovarian cancers. We found two somatic BRCA1 mutations in exon 11, one in a breast cancer and the other in an ovarian cancer, both of which result in truncated proteins. Our results indicate that somatic BRCA1 mutations, like somatic mutations in the BRCA2 gene, though very rare, can be found in both breast and ovarian cancers and support a tumor suppressor function for BRCA1 in sporadic tumors.

Biliary obstruction in hematopoietic cell transplant recipients: an uncommon diagnosis with specific causes.

Jaundice is a common problem in marrow transplant recipients. The incidence of bile duct obstruction in this setting is unknown. The purpose of this study was to determine the incidence of biliary obstruction, the causes, and outcomes following marrow transplant. Consecutive cases were reviewed at two major transplant centers in the United States from 1969 to 1996 at the Fred Hutchinson Cancer Research Center and 1989 to 1996 at the City of Hope National Medical Center. Nine cases of biliary obstruction were identified as a cause of jaundice in 7412 marrow transplant recipients, an incidence of 0.12%. The presentation was bimodal, with seven cases occurring prior to day 100 and two occurring 2 to 4 years after transplantation. The age distribution was 15 to 50 years and all patients had received allogeneic transplants. The causes of obstruction included gallbladder sludge (n=1), a duodenal hematoma (n=1), choledocholithiasis with biliary pancreatitis (n=1), bile duct infection (n=2), recurrent malignancy (n=1), choledocholithiasis associated with a benign stricture (n=1), Epstein-Barr virus-related lymphoproliferative disorder (n=1), and a benign stricture of unknown etiology (n=1). Biliary obstruction is a rare cause of jaundice in the post-transplant period. The presentation was similar to that of other post-transplant hepatobiliary problems, but with disparate causes.

Desmoplastic malignant melanoma on the buttock of an 18-year-old girl: differentiation from desmoplastic nevus.

Melanocytic proliferation in young people may sometimes pose a diagnostic dilemma. This is particularly so when a desmoplastic component is present. Because the two main differential diagnoses, desmoplastic malignant melanoma and desmoplastic Spitz nevus, share some morphologic features, the diagnosis of desmoplastic malignant melanoma may be overlooked. Distinction between the two is important because they show completely different biological behavior. The age of patient, site of lesion, histologic findings of melanocytic atypia, neurotropism, mitosis, and maturation help to distinguish the two entities. We report a case of desmoplastic malignant melanoma occurring in the buttock of an 18-year-old Chinese girl. Histologically, it had typical features of desmoplastic malignant melanoma with junctional melanocytic atypia and prominent neurotropism. Clinical and histologic differences between desmoplastic malignant melanoma and desmoplastic Spitz nevus are reviewed. We conclude that although desmoplastic Spitz nevus occurs much more commonly in adolescents, desmoplastic malignant melanoma can occur in this age group and even in non-sunexposed skin. Microscopic findings remain the mainstay that guides the final diagnosis.

Helicobacter pylori in Meckel's diverticulum with heterotopic gastric mucosa in a population with relatively high H. pylori prevalence rate.

BACKGROUND: Helicobacter pylori (H. pylori) colonize only foveolar gastric-type mucosa and are associated with active chronic gastritis and peptic ulcer. The aim of this study was to investigate whether H. pylori can also be found in Meckel's diverticulum which contains heterotopic gastric mucosa. METHODS: Biopsy specimens of Meckel's diverticulum resected in Queen Mary Hospital, University of Hong Kong, during the 10 year period 1986-1995 were retrieved and reviewed. Those containing gastric heterotopia were examined for the presence of H. pylori, using Warthin-Starry silver stain. RESULTS: In the 59 cases of Meckel's diverticula studied, 16 were found to contain heterotopic gastric mucosa. Helicobacter pylori were not identified in any of these cases. In one of the 16 patients a concomitant gastric biopsy was performed. Although the gastric mucosa of this patient was heavily colonized by H. pylori, again no H. pylori was found in the heterotopic gastric mucosa in the Meckel's diverticulum. CONCLUSIONS: The absence of H. pylori in all the Meckel's diverticula examined, even when the stomach was heavily colonized by the organisms, suggests that colonization of Meckel's diverticulum by H. pylori is a rare event. This, together with the overall rarity of H. pylori in all reported series of Meckel's diverticulum, argues against its causative role in complications of Meckel's diverticulum.