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Biomedical subjects

M Haas

Publications and source records attributed to M Haas.

At least 19 recordsLinked to original sources

Subclinical acute antibody-mediated rejection in positive crossmatch renal allografts.

Subclinical antibody-mediated rejection (AMR) has been described in renal allograft recipients with stable serum creatinine (SCr), however whether this leads to development of chronic allograft nephropathy (CAN) remains unknown. We retrospectively reviewed data from 83 patients who received HLA-incompatible renal allografts following desensitization to remove donor-specific antibodies (DSA). Ten patients had an allograft biopsy showing subclinical AMR [stable SCr, neutrophil margination in peritubular capillaries (PTC), diffuse PTC C4d, positive DSA] during the first year post-transplantation; 3 patients were treated with plasmapheresis and intravenous immunoglobulin. Three patients had a subsequent rise in SCr and an associated biopsy with AMR; 5 others showed diagnostic or possible subclinical AMR on a later protocol biopsy. One graft was lost, while remaining patients have normal or mildly elevated SCr 8-45 months post-transplantation. However, the mean increase in CAN score (cg + ci + ct + cv) from those biopsies showing subclinical AMR to follow-up biopsies 335 +/- 248 (SD) days later was significantly greater (3.5 +/- 2.5 versus 1.0 +/- 2.0, p = 0.01) than that in 24 recipients of HLA-incompatible grafts with no AMR over a similar interval (360 +/- 117 days), suggesting that subclinical AMR may contribute to development of CAN.

Adult↗

Altered vitamin D metabolism in type II diabetic mouse glomeruli may provide protection from diabetic nephropathy.

The db/db mouse develops features of type II diabetes mellitus as the result of impaired signaling through its abnormal leptin receptor. In spite of accurate metabolic features of diabetes, renal disease manifestations in these mice are not as severe as in humans suggesting the presence of protective genes. There is a growing body of evidence in humans for the relevance of vitamin D in diabetes. Here we followed a large cohort of db/db mice and their non-diabetic db/+ littermates. Transcriptional profiling revealed significant upregulation of 23 genes involved in Ca2+ homeostasis and vitamin D metabolism in db/db glomeruli relative to db/+ glomeruli. Increased glomerular expression of vitamin D3 1alpha-hydroxylase, vitamin D binding protein, calbindins D9K and D28K, and calcyclin mRNA was confirmed by quantitative reverse transcription-polymerase chain reaction in 20-, 36-, and 52-week-old db/db glomeruli. Although vitamin D3 1alpha-hydroxylase protein was primarily expressed and upregulated in db/db renal tubules, it was also expressed in glomerular podocytes in vivo. Serum 1,25-dihydroxyvitamin D3 and urinary Ca2+ excretion were increased >3-fold in db/db mice compared to db/+ mice. Cultured glomerular podocytes had mRNA for vitamin D3 1alpha-hydroxylase, vitamin D receptor, and calbindin D28K, each of which was increased in high glucose conditions. High glucose also led to enhanced production of fibronectin and collagen IV protein, which was blocked by 1,25-dihydroxyvitamin D3. These results show that vitamin D metabolism is altered in db/db mice leading to metabolic and transcriptional effects. The podocyte is affected by paracrine and potentially autocrine effects of vitamin D, which may explain why db/db mice are resistant to progressive diabetic nephropathy.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

[Drugs during pregnancy and breastfeeding: new risk categories--antibiotics as a model].

BACKGROUND AND OBJECTIVE: In selecting drugs for treatment during pregnancy and breastfeeding it is essential to be certain of their safety. But categories are lacking that systematically relate the current state of knowledge of individual substances--rather than just drug classes--to each trimester of pregnancy. As such a stratification of risk would be helpful, it was the aim of this study to propose a new and more differentiated classification. METHODS: Internationally available literature and electronic data bases providing details on adverse effects of individual drugs during pregnancy and breastfeeding as well as summaries of product characteristics of the drugs served as comprehensive sources of information. Account was taken of compound-specific data on toxicity during the reproductive and developmental stages, genotoxicity and carcinogenicity (in animals and in-vitro experiments) and drug-specific experience as documented in women during pregnancy and breastfeeding. RESULTS: A new risk classification and appropriate recommendations for clinical management were developed to ensure the safety of drugs given during pregnancy and breastfeeding, taking into account the varying risks during the three trimesters of pregnancy and the perinatal period. Antibiotics were selected as a model for drugs in general and classified according to the new system. CONCLUSION: The proposed new classification of risk makes it possible to select safe agents in the treatment of pregnant and/or breastfeeding women. It is based on the current state of knowledge about a particular substance, also in relationship to the developmental phase of the breastfed child.

Animals↗

Hypertension, race, and glomeruli: more than simply a numbers game.

Incidences of hypertension and hypertension-related renal failure are considerably higher in African-Americans than in white Americans. One explanation offered for this is that African-Americans have a higher incidence of low birth weight, the latter associated with lower numbers of glomeruli. However, although studies show a clear association between hypertension and glomerular number in whites, the situation in African-Americans appears more complex.

Adolescent↗

VEGF receptor 2 blockade leads to renal cyst formation in mice.

Polycystic kidney disease (PKD) is associated with mutations in PKD1 and PKD2 and vascular abnormalities. The links between the epithelial and vascular defects, however, are poorly understood. Vascular endothelial growth factor (VEGF) has been shown to be critical for normal kidney development. In animal models, blockade of VEGF in the perinatal period can lead to abnormal glomerular development, impaired nephrogenesis, proteinuria, and renal failure. We hypothesized that brief blockade of VEGF signaling during early postnatal kidney development can lead to renal cyst development. On days 2 and 4 of life, CD-1 mice were treated with antibodies generated against the extracellular portion of the VEGF receptor 2 (DC101), the area of the receptor where VEGF binding occurs. Mice developed renal cysts between 2 and 3 weeks. The DC101-treated mice also had increased cell proliferation in the renal tubule epithelium. In addition, mice receiving DC101 developed abnormal glomeruli, proteinuria, and patchy cellular infiltrates. Early disruption of VEGFR-2 signaling during the perinatal period results in renal cyst formation, impaired glomerulogenesis, and inflammation. VEGF could be a key link between vascular and cystic changes in kidney cyst formation.

Animals↗

Effect of kidney transplantation on bone.

A broad range of different factors aggravates renal osteodystrophy, which is present in virtually all patients with chronic kidney disease and after successful kidney transplantation. Altered hormonal status, including sex hormones and parathyroid hormone (PTH), a deficit of 1,25(OH)(2) vitamin D(3) (calcitriol), immunosuppressive therapy and post-operative immobilization contribute to a progressive loss of bone density and structure. The decrease of bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures, both compared with the normal population as well as with dialysis patients. At particular risk are patients with a history of diabetes, long duration of haemodialysis and post-menopausal women. To prevent post-transplant bone loss prescription of steroids should be minimized and withdrawn as early as possible. Additional intake of alpha-calcidol [25(OH) vitamin D(3)] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to effectively reverse bone loss during the early and late course of kidney transplantation. However, as the majority of transplant recipients have a low-turnover bone disease, inhibition of osteoclasts, through which bone turnover is impaired, might further reduce osteoblast activity and promote osteoid synthesis. Most investigations were small-scale studies with 10-100 participants and a follow up of only 12 months. This makes conclusions on the effect of any intervention on the fracture rate impossible. Larger, randomized multicentre studies investigating bone-sparing therapy on hard end points are therefore advocated.

Bone Density↗

C4d and C3d staining in biopsies of ABO- and HLA-incompatible renal allografts: correlation with histologic findings.

Biopsies of ABO-incompatible and positive crossmatch (HLA-incompatible) renal allografts were retrospectively examined to compare results of C4d and C3d staining, and the correlation between such staining and histologic findings suggestive of antibody-mediated rejection (AMR). A total of 75 biopsies (55 protocol, 17 for graft dysfunction, 3 for other indications) of 24 ABO-incompatible grafts and 244 biopsies (103 protocol, 129 for graft dysfunction, 12 for other indications) of 66 HLA-incompatible grafts were examined; all were stained for C4d and approximately 40% for C3d. In ABO-incompatible grafts, 80% of protocol biopsies and 59% performed for graft dysfunction showed C4d staining in peritubular capillaries (PTC); this staining was not correlated with neutrophil margination in PTC. In HLA-incompatible grafts, PTC C4d was present in 26% of protocol biopsies and 60% of biopsies for graft dysfunction; 92% of biopsies with >1+ (0-4+ scale), diffuse PTC C4d had > or =1+ margination and/or thrombotic microangiopathy (TMA), compared with 12% of C4d-negative biopsies. C3d was somewhat more predictive of margination than C4d in ABO-incompatible, but not HLA-incompatible, grafts. In summary, while PTC C4d deposition indicates probable AMR in biopsies of HLA-incompatible grafts, including protocol biopsies, there is no histologic evidence that C4d deposition is correlated with injury in most ABO-incompatible grafts.

ABO Blood-Group System↗

Hydroxychloroquine use predicts complete renal remission within 12 months among patients treated with mycophenolate mofetil therapy for membranous lupus nephritis.

The objective of this study was to identify clinical predictors of response to initial mycophenolate mofetil (MMF) therapy for membranous lupus nephritis (MLN). We observed the clinical outcomes of patients in the Hopkins Lupus Cohort within the first year of initiation of treatment with MMF therapy for newly diagnosed MLN, classified according to the new International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification. Complete renal remission was defined as proteinuria less than 500 mg/24 hours. Demographic, clinical, treatment and laboratory data were examined for their association with renal remission. Twenty-nine MLN patients treated with MMF were identified. Eleven (38%) patients achieved complete renal remission by 12 months. Of those taking hydroxychloroquine, 7/11 (64%) were in remission within 12 months compared to only 4/18 (22%) of those not on hyroxychloroquine (P = 0.036 based on a log-rank test). This association persisted after controlling for the presence of anti-ds-DNA (P = 0.026). Our results provide evidence that hydroxychloroquine has a benefit for renal remission when MMF is used as the initial therapy for MLN. Although hydroxychloroquine is frequently stopped in patients with lupus nephritis, this study suggests it should be started or maintained.

Adolescent↗

Impact on postoperative pain of long-lasting pre-emptive epidural analgesia before total hip replacement: a prospective, randomised, double-blind study.

Clinical studies on pre-emptive analgesia have produced inconsistent results. We conducted a clinical study investigating the effect of long-lasting pre-emptive epidural analgesia on consumption of analgesics and acute pain. Forty-two patients scheduled for elective hip replacement for osteo-arthritis were randomly assigned to receive, on the day before operation, either 5 ml.h(-1) ropivacaine 0.2% (study group, n = 21) or 5 ml.h(-1) saline (control group, n = 21). Postoperative analgesia was achieved in both groups by patient-controlled epidural analgesia (PCEA) with ropivacaine 0.2%. The main outcome measure was consumption of local anaesthetics. Additional parameters included visual analogue pain scale (VAS) scores, consumption of rescue analgesics, requests for PCEA boluses, and side-effects. The pre-operative parameters and pain scores were similar in the two groups. Epidural blocks provided sufficient operative analgesia in all patients. Pre-emptive analgesia was continued for 11-20 h and led to significantly decreased pain scores before surgery. The consumption of local anaesthetics was decreased postoperatively in the study group (194 mg vs. 284 mg in the postoperative period). Furthermore, bolus requests occurred more frequently in the control group. VAS scores did not differ significantly between groups. Long-lasting "pre-emptive" epidural analgesia decreases postoperative pain with improved pain control.

Adult↗

New limits on the drift of fundamental constants from laboratory measurements.

We have remeasured the absolute 1S-2S transition frequency nu(H) in atomic hydrogen. A comparison with the result of the previous measurement performed in 1999 sets a limit of (-29+/-57) Hz for the drift of nu(H) with respect to the ground state hyperfine splitting nu(Cs) in 133Cs. Combining this result with the recently published optical transition frequency in 199Hg+ against nu(Cs) and a microwave 87Rb and 133Cs clock comparison, we deduce separate limits on alpha/alpha=(-0.9+/-2.9) x 10(-15) yr(-1) and the fractional time variation of the ratio of Rb and Cs nuclear magnetic moments mu(Rb)/mu(Cs) equal to (-0.5+/-1.7) x 10(-15) yr(-1). The latter provides information on the temporal behavior of the constant of strong interaction.

Journal Article↗

Randomized controlled trial of yoga and exercise in multiple sclerosis.

OBJECTIVE: To determine the effect of yoga and of aerobic exercise on cognitive function, fatigue, mood, and quality of life in multiple sclerosis (MS). METHODS: Subjects with clinically definite MS and Expanded Disability Status Score less than or equal to 6.0 were randomly assigned to one of three groups lasting 6 months: weekly Iyengar yoga class along with home practice, weekly exercise class using a stationary bicycle along with home exercise, or a waiting-list control group. Outcome assessments performed at baseline and at the end of the 6-month period included a battery of cognitive measures focused on attention, physiologic measures of alertness, Profile of Mood States, State-Trait Anxiety Inventory, Multi-Dimensional Fatigue Inventory (MFI), and Short Form (SF)-36 health-related quality of life. RESULTS: Sixty-nine subjects were recruited and randomized. Twelve subjects did not finish the 6-month intervention. There were no adverse events related to the intervention. There were no effects from either of the active interventions on either of the primary outcome measures of attention or alertness. Both active interventions produced improvement in secondary measures of fatigue compared to the control group: Energy and Fatigue (Vitality) on the SF-36 and general fatigue on the MFI. There were no clear changes in mood related to yoga or exercise. CONCLUSION: Subjects with MS participating in either a 6-month yoga class or exercise class showed significant improvement in measures of fatigue compared to a waiting-list control group. There was no relative improvement of cognitive function in either of the intervention groups.

Adult↗

Non-invasive physical treatments for chronic/recurrent headache.

BACKGROUND: Non-invasive physical treatments are often used to treat common types of chronic/recurrent headache. OBJECTIVES: To quantify and compare the magnitude of short- and long-term effects of non-invasive physical treatments for chronic/recurrent headaches. SEARCH STRATEGY: We searched the following databases from their inception to November 2002: MEDLINE, EMBASE, BIOSIS, CINAHL, Science Citation Index, Dissertation Abstracts, CENTRAL, and the Specialised Register of the Cochrane Pain, Palliative Care and Supportive Care review group. Selected complementary medicine reference systems were searched as well. We also performed citation tracking and hand searching of potentially relevant journals. SELECTION CRITERIA: We included randomized and quasi-randomized controlled trials comparing non-invasive physical treatments for chronic/recurrent headaches to any type of control. DATA COLLECTION AND ANALYSIS: Two independent reviewers abstracted trial information and scored trials for methodological quality. Outcomes data were standardized into percentage point and effect size scores wherever possible. The strength of the evidence of effectiveness was assessed using pre-specified rules. MAIN RESULTS: Twenty-two studies with a total of 2628 patients (age 12 to 78 years) met the inclusion criteria. Five types of headache were studied: migraine, tension-type, cervicogenic, a mix of migraine and tension-type, and post-traumatic headache. Ten studies had methodological quality scores of 50 or more (out of a possible 100 points), but many limitations were identified. We were unable to pool data because of study heterogeneity. For the prophylactic treatment of migraine headache, there is evidence that spinal manipulation may be an effective treatment option with a short-term effect similar to that of a commonly used, effective drug (amitriptyline). Other possible treatment options with weaker evidence of effectiveness are pulsating electromagnetic fields and a combination of transcutaneous electrical nerve stimulation [TENS] and electrical neurotransmitter modulation. For the prophylactic treatment of chronic tension-type headache, amitriptyline is more effective than spinal manipulation during treatment. However, spinal manipulation is superior in the short term after cessation of both treatments. Other possible treatment options with weaker evidence of effectiveness are therapeutic touch; cranial electrotherapy; a combination of TENS and electrical neurotransmitter modulation; and a regimen of auto-massage, TENS, and stretching. For episodic tension-type headache, there is evidence that adding spinal manipulation to massage is not effective. For the prophylactic treatment of cervicogenic headache, there is evidence that both neck exercise (low-intensity endurance training) and spinal manipulation are effective in the short and long term when compared to no treatment. There is also evidence that spinal manipulation is effective in the short term when compared to massage or placebo spinal manipulation, and weaker evidence when compared to spinal mobilization. There is weaker evidence that spinal mobilization is more effective in the short term than cold packs in the treatment of post-traumatic headache. REVIEWERS' CONCLUSIONS: A few non-invasive physical treatments may be effective as prophylactic treatments for chronic/recurrent headaches. Based on trial results, these treatments appear to be associated with little risk of serious adverse effects. The clinical effectiveness and cost-effectiveness of non-invasive physical treatments require further research using scientifically rigorous methods. The heterogeneity of the studies included in this review means that the results of a few additional high-quality trials in the future could easily change the conclusions of our review.

Chronic Disease↗

A rare cause of anemia due to intestinal tuberculosis in a renal transplant recipient.

A renal transplant recipient with stable allograft function presented with massive hemorrhagic diarrhea and severe anemia. No microbial infection could be found in stool cultures. Early colonoscopy showed severe colitis with ulceration. Histological samples confirmed granulomatous inflammation with acid-resistant Ziehl-Neelson-positive microorganisms of mycobacterial type. Polymerase chain reaction (PCR) analysis of native mucosal biopsies specified the infectious organism as Mycobacterium tuberculosis complex. The patient responded well to antimycobacterial therapy and was still asymptomatic after 6 months with a stable graft function. Our case shows that tuberculosis can be a severe clinical problem in transplant recipients. Most of the patients with intestinal tuberculosis, reported to literature, were diagnosed post mortem or after explorative laparotomy and bowel resection. Thus, intestinal tuberculosis should be considered when a transplant recipient shows abdominal symptoms with no clear evidence of another infection. Proper diagnosis and treatment resulted in a beneficial outcome in our patient.

Anemia↗

Platelets and capillary injury in acute humoral rejection of renal allografts.

Platelet accumulation in glomerular capillaries (GC) and peritubular capillaries (PC) has pathogenetic importance in antibody-mediated hyperacute renal allograft rejection. CD61 is expressed constitutively by platelets, by platelet microparticles arising from platelet activation, and is readily detectable by immunohistochemistry. This study examined the immunohistochemical localization of CD61 in acute humoral rejection (AHR) of renal allografts to explore the relationship of platelet accumulation to antibody-mediated rejection. Two observers graded the extent of CD61 staining in PC and GC from 0 (none) to 2+ (>50%) in 15 renal allograft biopsy specimens with AHR and compared these with tissues from allografts with acute cellular rejection (ACR) (n = 23); acute calcineurin inhibitor toxicity (ACIT) (n = 21) with thrombotic microangiopathy (TMA) (n = 11) and tubular toxicity only (n = 10); acute tubular necrosis (ATN) (n = 16); acute renal vein thrombosis (RVT) (n = 4); and histologically unremarkable native kidneys (n = 26). Selected tissues were examined by electron microscopy and stained for CD34 by immunohistochemistry. Histologically unremarkable native kidney tissues had CD61 only in scattered small lumenal granules in GC and PC. Mural and occlusive lumenal CD61 deposits (>0.5+) were observed in 13 of 13 (100%) allograft tissues with GC thrombi due to AHR (1) and ACIT TMA (9) and RVT (3). Twenty-seven of 66 allografts (40.9%) without glomerular thrombi had >0.5+ GC CD61 in AHR (60%), ACR (26%), tubular ACIT (60%), and ATN (44%). More than trace (>0.5+) PC mural and lumenal CD61 deposits were seen only in AHR (53.3%) and ACR (30%). PC CD61 correlated with interstitial hemorrhage (r = 0.64), neutrophilic capillaritis (r = 0.47), and interstitial inflammation (r = 0.47) (P <0.001 for each). PC CD61 was observed in 11 of 11 foci of necrosis due to AHR, RVT, and ischemia. In AHR, capillaries with CD61 deposits had few platelets, numerous microvesicles and membrane fragments, severe endothelial injury seen on electron microscopy, and reduced capillary CD34 expression. CD61 detection by immunohistochemistry revealed products of capillary platelet activation in allograft biopsy specimens without light microscopic thrombi. Observations in this study suggest that intracapillary platelet activation occurs in response to graft capillary injury from many causes and may not be specific for antibody-mediated rejection.

Acute Disease↗

A study of the impact of long-term tobacco smoking on postoperative intensive care admission.

Smoking is a risk factor for intra-operative pulmonary complications and a wide range of postoperative pulmonary, cardiovascular, infection and wound-related complications. These may all lead to unplanned postoperative intensive care admission. We tested the hypothesis that smokers have an increased incidence of postoperative intensive care admission and more postoperative complications than nonsmokers in a general and orthopaedic surgical population. The following information was assessed in 6026 surgical patients: age, sex and smoking status (pack-years), history of heart and lung disease, American Society of Anesthesiologists (ASA) physical classification, intensive care admission and postoperative complications. Two thousand five hundred and twenty-six (46%) were smokers but for 620 patients (10.3%) smoking status was not confirmed. Postoperative intensive care admission was required by 319 patients (5.3%). Patients with > 50 pack-years were admitted to the intensive care more frequently than were smokers with < or = 50 pack-years history and nonsmokers (p < 0.001). Ex-smokers with > 50 pack-years history had the same risk of postoperative admission to intensive care as smokers with > 50 pack-years history. Smokers admitted to intensive care with > 50 pack-years history had a higher incidence of chronic lung disease (p < 0.005) and heavy alcohol consumption (p < 0.001). These smokers also had a higher incidence of postoperative pulmonary complications (odds ratio = 3.91, p < 0.01). The mortality rate was 37% in smokers with > 50 pack-years history and 24% in nonsmokers (odds ratio = 2.02, p = 0.08). We conclude long-term tobacco smoking (> 50 pack-years) carries a higher risk of postoperative admission to intensive care, and there seems to be a dose relationship between the amount of tobacco consumed and the risk of postoperative intensive care admission.

Adult↗