A rare presentation of a common disease.
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Biomedical subjects
Publications and source records attributed to H Patel.
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A 10-year retrospective review of 15 children with cerebral tumors and seizures was conducted to study the factors responsible for delay in the diagnosis of tumors and to assess outcome following surgery. Mean duration of seizures prior to surgery was 37 months. Ninety-three percent had no focal neurologic deficits. Head computed tomography was abnormal in 64%, whereas magnetic resonance imaging was abnormal in all patients. Electroencephalography showed focal abnormalities ipsilateral to the tumor in 73%. There was no surgical mortality. Eighty percent were seizure free or had rare seizures following surgery. Factors contributing to a delayed diagnosis of the brain tumor included a nonfocal neurologic examination and delay in obtaining an appropriate neuroimaging study. We believe that head magnetic resonance imaging should be the investigation of choice in partial epilepsies.
Previous studies have suggested that the helical repeat formed by residues 143;-164 of apolipoprotein A-I (apoA-I) contributes to lecithin:cholesterol acyltransferase (LCAT) activation. To identify specific polar residues involved in this process, we examined residue conservation and topology of apoA-I from all known species. We observed that the hydrophobic/hydrophilic interface of helix 143;-164 contains a cluster of three strictly conserved arginine residues (R149, R153, and R160), and that these residues create the only significant positive electrostatic potential around apoA-I. To test the importance of R149, R153, and R160 in LCAT activation, we generated a series of mutant proteins. These had fluorescence emission, secondary structure, and lipid-binding properties comparable to those of wild-type apoA-I. Mutation of conserved residues R149, R153, and R160 drastically decreased LCAT activity on lipid-protein complexes, whereas control mutations (E146Q, D150N, D157N, R171Q, and A175R) did not decrease LCAT activity by more than 55%. The markedly decreased activities of mutants R149, R153, and R160 resulted from a decrease in the maximal reaction velocity V(max) because the apparent Michaelis-Menten constant K(m) values were similar for the mutant and wild-type apoA-I proteins. These data suggest that R149, R153, and R160 participate in apoA-I-mediated activation of LCAT, and support the "belt" model for discoidal rHDL. In this model, residues R149, R153, and R160 do not form salt bridges with the antiparallel apoA-I monomer, but instead are pointing toward the surface of the disc, enabling interactions with LCAT. - Roosbeek, S., B. Vanloo, N. Duverger, H. Caster, J. Breyne, I. De Beun, H. Patel, J. Vandekerckhove, C. Shoulders, M. Rosseneu, and F. Peelman. Three arginine residues in apolipoportein A-I are critical for activation of lecithin:cholesterol acyltransferase J. Lipid Res. 2001. 42: 31;-40.
OBJECTIVE: To review office interventions for minor wounds not requiring sutures, such as abrasions, bites, and lacerations. QUALITY OF EVIDENCE: Most information on minor wound management comes from descriptive studies. Few comparative studies examine the effectiveness of topical antisepsis for minor wounds. Several clinical trials have demonstrated that tissue adhesives produce short- and long-term cosmetic results equivalent to those achieved with suture materials. MAIN MESSAGE: Sterile saline is the least toxic solution for wound irrigation. Chlorhexidine (2%) and povidone iodine (10%) have been the most investigated antiseptic solutions. Systemic antibiotics are unnecessary for wounds unlikely to be infected. All bite wounds require special attention. Primary closure of bite wounds is indicated in certain circumstances: less than 12-hour-old nonpuncture wounds, uninfected wounds, and low-risk lesions (such as on the face). In spite of their many advantages, skin tapes should be used for low-tension wounds only. The popularity of tissue adhesives has greatly increased. Since the advent of newer products (with increased bonding strength and flexibility), adhesives are used to manage most lacerations except those in areas of high tension (e.g., joints) and on mucosal surfaces. CONCLUSION: Minor wounds not requiring sutures can be managed easily in the office.
An economic model was developed to estimate the relative cost-effectiveness of alternative HMG-CoA reductase inhibitors (statins)--atorvastatin, cerivastatin, fluvastatin, pravastatin and simvastatin--to achieve target low-density lipoprotein cholesterol (LDL-C) levels in a population of secondary CHD prevention patients. By using a cholesterol target as the endpoint of interest and a dose titration approach, the model assumes that the statins demonstrate a class effect through cholesterol lowering. The model was used to estimate the proportion of patients achieving target LDL-C levels (< 3 mmol/l) under each scenario tested. Total costs and incremental cost-effectiveness relative to no treatment and to the lowest cost option were estimated for each scenario. Total costs were highest for pravastatin and lowest for cerivastatin. Compared with no treatment, the incremental cost per patient treated to target LDL-C varied between 383 Pounds (atorvastatin) and 1213 Pounds (pravastatin). Incremental cost-effectiveness ratios in comparison with the lowest cost treatment (cerivastatin) were 141 Pounds per additional patient achieving target LDL-C with atorvastatin, and 275 Pounds with simvastatin. Fluvastatin and pravastatin were both less effective and more expensive than the lowest cost therapy. Although cerivastatin was associated with lowest expected costs, therapy with atorvastatin achieved the lowest cost-effectiveness ratios. Hence atorvastatin would allow the largest number of patients to be treated to target LDL-C within a fixed drug budget. Choosing between drug therapies on the basis of price alone may be misleading if the effectiveness of therapies varies.
Dictyostelium development starts with the chemotactic aggregation of up to 10(6) amoebae in response to propagating cAMP waves. cAMP is produced by the aggregation stage adenylyl cyclase (ACA) and cells lacking ACA (aca null) cannot aggregate. Temperature-sensitive mutants of ACA were selected from a population of aca null cells transformed with a library of ACA genes, a major segment of which had been amplified by error-prone PCR. One mutant (tsaca2) that can complement the aggregation null phenotype of aca null cells at 22 degrees C but not at 28 degrees C was characterized in detail. The basal catalytic activity of the enzyme in this mutant was rapidly and reversibly inactivated at 28 degrees C. Using this mutant strain we show that cell movement in aggregates and mounds is organized by propagating waves of cAMP. Synergy experiments between wild-type and tsaca2 cells, shifted to the restrictive temperature at various stages of development, showed that ACA plays an important role in the control of cell sorting and tip formation.
Scallop striated adductor muscle myosin is a regulatory myosin, its activity being controlled directly through calcium binding. Here, we show that millimolar concentrations of trifluoperazine were effective at removal of all regulatory light chains from scallop myosin or myofibrils. More important, 200 microM trifluoperazine, a concentration 10-fold less than that required for light-chain removal, resulted in the reversible elimination of actin-activated and intrinsic ATPase activities. Unlike desensitization induced by metal ion chelation, which leads to an elevation of activity in the absence of calcium concurrent with regulatory light-chain removal, trifluoperazine caused a decline in actin-activated MgATPase activity both in the presence and absence of calcium. Procedures were equally effective with respect to scallop myosin, myofibrils, subfragment-1, or desensitized myofibrils. Increased alpha-helicity could be induced in the isolated essential light chain through addition of 100-200 microM trifluoperazine. We propose that micromolar concentrations of trifluoperazine disrupt regulation by binding to a single high-affinity site located in the C-terminal domain of the essential light chain, which locks scallop myosin in a conformation resembling the off-state. At millimolar trifluoperazine concentrations, additional binding sites on both light chains would be filled, leading to regulatory light-chain displacement.
Two genes encoding thioredoxin are found on the Escherichia coli genome. Both of them are capable of reducing protein disulfide bonds in vivo and in vitro. The catalytic site contains a Cys-X(1)-X(2)-Cys motif in a so-called thioredoxin fold. Thioredoxin 2 has two additional pairs of cysteines in a non-conserved N-terminal domain. This domain does not appear to be important for the function of thioredoxin 2 in donating electrons to ribonucleotide reductase, 3'-phosphoadenylsulfate-reductase, or the periplasmic disulfide isomerase DsbC. Our results suggests that the two thioredoxins are equivalent for most of the in vivo functions that were tested. On the other hand, transcriptional regulation is different. The expression of trxC is regulated by the transcriptional activator OxyR in response to oxidative stress. Oxidized OxyR binds directly to the trxC promoter and induces its expression in response to elevated hydrogen peroxide levels or the disruption of one or several of the cytoplasmic redox pathways. Mutants lacking thioredoxins 1 and 2 are more resistant to high levels of hydrogen peroxide, whereas they are more sensitive to diamide, a disulfide bond-inducing agent.
BACKGROUND: Children with symptoms and signs of constipation are commonly assessed in pediatric emergency departments (EDs). Little is known about their outcome following the ED visit. OBJECTIVES: To describe the clinical characteristics of children presenting to the ED with constipation and the ED interventions; to measure short-term symptom resolution at 48 hours and 7 days after the ED visit; and to identify predictive factors associated with poor symptom resolution at 48 hours and 7 days after the ED visit. DESIGN/METHODS: Cohort study conducted between July 10, 1997, and September 10, 1997, in a tertiary care pediatric hospital ED. All children (aged 1-18 years) with idiopathic constipation were included. Constipation was diagnosed if there were at least 2 of the following: abdominal pain, infrequent bowel movements, hard feces, fecal soiling, pain on defecation, and/or clinical evidence of excessively retained feces. Data on the presenting symptoms, signs, and ED treatment plan were collected on study enrollment and then in 2 standardized 10-minute telephone interviews at 48 hours and 7 days after the ED visit. At each follow-up, patient disposition was measured and dichotomized based on symptom resolution to "improved" vs "not improved." The presenting features and ED management were compared between groups using chi(2) analyses and t tests. RESULTS: Consent and full questionnaire completion was obtained in 102 children. The mean + SD age was 6.5 + 3.8 years; 47 (46%) were male. The predominant presenting symptom was abdominal pain (83 [81%]); the most frequent sign was palpable abdominal stool (67 [66%]). A high-fiber diet (75 [74%]) and mineral oil (48 [47%]) were prescribed most frequently. Enemas were given to 64 (63%) of the children. Improvement was found in 32 (31%) of the children at 48 hours and in the majority at 7 days (77 [75%]). Risk factors for poor symptom resolution at both 48 hours and 1 week included: female sex (odds ratio [OR] = 2.6; 95% confidence interval [CI] = 1.0 6.6); history of recurrent abdominal pain (OR = 2.8; 95% CI = 1.2-6.5); duration of primary presenting symptom longer than 2 days (OR = 2.4; 95% CI = 1.0-6.4); and history of medical visits for the same symptom (OR = 2.3; 95% CI = 1.0-5.3). There was no difference in outcome based upon ED treatment (enema vs oral or no therapy) (OR = 1.0; 95% CI = 0.4-2.3). CONCLUSIONS: Most children with constipation evaluated in the ED have acute symptoms and rapid improvement, regardless of presentation characteristics or ED management. In this study, 4 risk factors for poor outcome were found consistently at 48 hours and 7 days. This subgroup of children deserve closer clinical attention. Emergency department therapy did not influence short-term symptom resolution. Further studies are warranted to examine the effects of therapy for constipation in the ED setting. Arch Pediatr Adolesc Med. 2000;154:1204-1208.
Atlanto-axial subluxation with torticollis is an uncommon condition that occurs in children usually as a result of pharyngeal infection, minor trauma, or neck surgery. Passive motion of the head and neck during general anesthesia is probably another etiologic factor. Torticollis is the most common presenting physical finding. Pain may or may not be present, but is commonly present with passive neck motion. Neurologic sequelae are uncommon. Our case illustrates this condition as a complication of central venous catheter (CVC) insertion in a child under general anesthesia. The surgeon should suspect this pathology when a child presents with torticollis following CVC placement. Precautions should be taken in the operating room to avoid aggressive rotation and extension of the child's neck while under general anesthesia whether or not cervical inflammation is present. Special attention to head and neck positioning should be taken in patients with Down's syndrome since they are at increased risk for atlanto-axial subluxation. The prognosis is excellent when diagnosed early. A delay in diagnosis can result in the need for surgical intervention.
Injuries to the major pulmonary vessels are uncommon and are extremely difficult to manage. We report a case of an isolated pulmonary vein injury following a road traffic accident that was repaired successfully.
OBJECTIVES: To demonstrate the incidence of positive urinary nuclear matrix protein 22 (NMP22) values associated with renal cell carcinoma (RCC) of the kidney. Currently, urinary NMP22 is used to detect recurrent transitional cell carcinoma of the bladder. METHODS: From May 1997 to March 1998, urinary NMP22 values were obtained from 65 patients who had undergone either computed tomography scanning of the abdomen or renal ultrasound. Of the 65, 32 presented with solid renal masses. These patients underwent radical or partial nephrectomy; subsequent pathologic examination revealed that 30 had RCC. Two patients had oncocytomas. The remaining 33 patients presented with blunt abdominal trauma or abdominal pain or for follow-up for a urologic problem (a kidney stone or benign renal cyst). These patients had no evidence of renal malignancy on imaging and were used as controls. RESULTS: The urinary NMP22 values of patients with RCC were significantly higher than the values found in the control group (13.69 +/- 8.40 U/mL versus 3.03 +/- 2.70 U/mL, P <0.0078). Of the 30 patients with RCC, 12 (40%) had positive urinary NMP22 values of 10 U/mL or above. Chi-square analysis revealed a significant difference between the NMP22 values of the two groups (P <0.005). There were two false-positive NMP22 values in the 35 control patients. CONCLUSIONS: Urinary NMP22 values used to detect transitional cell carcinoma in individuals with previously diagnosed bladder cancer should be more broadly evaluated, since elevations have also been found to occur in RCC of the kidney. This finding may result in an increase in the incidental discovery of RCC. Future, more specific, NMP assays may hold promise for the detection of RCC.
OBJECTIVES: To evaluate the corrected Thrombolysis in Myocardial Infarction (TIMI) frame count (CTFC) as a predictor of late survival after myocardial infarction. BACKGROUND: Thrombolysis in Myocardial Infarction flow grades predict late survival after myocardial infarction. The CTFC provides a more reproducible measurement of infarct-related artery blood flow than the TIMI flow grade, and has been linked to 30-day outcomes, but it has not yet been established how the CTFC correlates with late survival. METHODS: Of 1,001 patients with acute myocardial infarction presenting within 4 h of symptom onset, 882 underwent angiography at approximately three weeks. Infarct artery flow was assessed, blinded to clinical outcomes, according to the CTFC and TIMI flow grade. Late cardiac mortality and survival were determined in 97.5% of patients. RESULTS: The mean CTFC was 40 +/- 29 in 644 patent infarct arteries (median, 34 [interquartile range, 24 to 47]). The CTFC, assessed as a continuous univariate variable, was found to be a predictor of five-year survival, as was the TIMI flow grade (both p < 0.001). On multivariate analysis, factors associated with five-year survival included the ejection fraction or end-systolic volume index (both p < 0.001); exercise duration (p = 0.005), age (p = 0.008), diabetes (p = 0.02) and CTFC (p = 0.02) or TIMI flow (p = 0.02). The same factors, except for the CTFC and TIMI flow grade, were predictors of 10-year survival. CONCLUSIONS: The CTFC three weeks after myocardial infarction was an independent predictor of five-year survival, but not 10-year survival. Although the CTFC provided additional prognostic information within TIMI flow grades, its superiority was not demonstrated.
We have determined the complete cDNA and deduced amino acid sequences of the heavy chain, regulatory light chain and essential light chain which constitute the molecular structure of myosin from the striated adductor muscle of the scallop, Pecten maximus. The deduced amino acid sequences of P. maximus regulatory light chain, essential light chain and heavy chain comprise 156, 156 and 1940 amino acids, respectively. These myosin peptide sequences, obtained from the most common of the eastern Atlantic scallops, are compared with those from three other molluscan myosins: the striated adductor muscles of Argopecten irradians and Placopecten magellanicus, and myosin from the siphon retractor muscle of the squid, Loligo pealei. The Pecten heavy chain sequence resembles those of the other two scallop sequences to a much greater extent as compared with the squid sequence, amino acid identities being 97.5% (A. irradians), 95.6% (P. magellanicus) and 73.6% (L. pealei), respectively. Myosin heavy chain residues that are known to be important for regulation are conserved in Pecten maximus. Using these Pecten sequences, we have overexpressed the regulatory light chain, and a combination of essential light chain and myosin heavy chain fragment, separately, in E. coli BL21 (DE3) prior to recombination, thereby producing Pecten regulatory domains without recourse to proteolytic digestion. The expressed regulatory domain was shown to undergo a calcium-dependent increase (approximately 7%) in intrinsic tryptophan fluorescence with a mid-point at a pCa of 6.6.
We assessed whether circulating cell positivity using RT-PCR for carcinoembryonic antigen (CEA) cDNA was affected by venesection via a needle compared with a pre-aspirated venous cannula, and by increased PCR cycles. Systemic blood was sampled by needle and pre-aspirated cannula in 101 healthy individuals with no cancer history. After erythrocyte removal, samples were subjected to RT-PCR using specific primers for CEA, with 29 or 35 RT-PCR cycles. There was a significant difference between the number of subjects whose samples were negative when collected via needle venesection and positive when collected via pre-aspirated cannula, compared with positive by needle venesection and negative by pre-aspirated cannula for both 29 (P = 0.016) and 35 (P = 0.0111) RT-PCR cycles. Venesection technique (P = 0.01) and number of cycles (P = 0.003) were significant predictors of a positive result. Positive results in healthy subjects were reduced to less than 3% when an aspirated cannula was used for venesection and >29 PCR cycles were avoided.
Boerhaave's syndrome is the condition of spontaneous rupture of the esophagus as a consequence of the strain of emesis with or without predisposing esophageal disease. It is a condition with high mortality. We describe four patients who underwent a transthoracic esophagectomy to remove the rupture of the intrathoracic esophagus, closure of the esophageal gastric junction, fashioning of a feeding gastrostomy, and formation of a left cervical esophagostomy. Three patients underwent reconstruction with subcutaneous colon. We suggest that this method of management may be considered where primary repair is impossible in those patients too ill for prolonged reconstruction or as a salvage procedure where other methods have failed. The poor quality of life after esophagectomy is improved by reconstruction. Other surgical options include covering the repaired opening with a circumferential wrap of pleura, chest wall muscle, or omentum or closing the repair around a T-tube of large caliber. Esophageal exclusion using absorbable staples is another approach.
Clinical studies of the treatment of glioma and cutaneous melanoma using boron neutron capture therapy (BNCT) are currently taking place in the USA, Europe and Japan. New BNCT clinical facilities are under construction in Finland, Sweden, England and California. The observation of transient acute effects in the oral mucosa of a number of glioma patients involved in the American clinical trials, suggests that radiation damage of the oral mucosa could be a potential complication in future BNCT clinical protocols, involving higher doses and larger irradiation field sizes. The present investigation is the first to use a high resolution surface analytical technique to relate the microdistribution of boron-10 (10B) in the oral mucosa to the biological effectiveness of the 10B(n,alpha)7Li neutron capture reaction in this tissue. The two boron delivery agents used clinically in Europe/Japan and the USA, borocaptate sodium (BSH) and p-boronophenylalanine (BPA), respectively, were evaluated using a rat ventral tongue model. 10B concentrations in various regions of the tongue mucosa were estimated using ion microscopy. In the epithelium, levels of 10B were appreciably lower after the administration of BSH than was the case after BPA. The epithelium:blood 10B partition ratios were 0.2:1 and 1:1 for BSH and BPA respectively. The 10B content of the lamina propria was higher than that measured in the epithelium for both BSH and BPA. The difference was most marked for BSH, where 10B levels were a factor of six higher in the lamina propria than in the epithelium. The concentration of 10B was also measured in blood vessel walls where relatively low levels of accumulation of BSH, as compared with BPA, was demonstrated in blood vessel endothelial cells and muscle. Vessel wall:blood 10B partition ratios were 0.3:1 and 0.9:1 for BSH and BPA respectively. Evaluation of tongue mucosal response (ulceration) to BNC irradiation indicated a considerably reduced radiation sensitivity using BSH as the boron delivery agent relative to BPA. The compound biological effectiveness (CBE) factor for BSH was estimated at 0.29 +/- 0.02. This compares with a previously published CBE factor for BPA of 4.87 +/- 0.16. It was concluded that variations in the microdistribution profile of 10B, using the two boron delivery agents, had a significant effect on the response of oral mucosa to BNC irradiation. From a clinical perspective, based on the findings of the present study, it is probable that potential radiation-induced oral mucositis will be restricted to BNCT protocols involving BPA. However, a thorough high resolution analysis of 10B microdistribution in human oral mucosal tissue, using a technique such as ion microscopy, is a prerequisite for the use of experimentally derived CBE factors in clinical BNCT.