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Biomedical subjects

D Hawkins

Publications and source records attributed to D Hawkins.

At least 37 records · Page 2Linked to original sources
PubMed2001

About 8- and approximately 84-h rhythms in endotheliocytes as in endothelin-1 and effect of trauma.

Population densities (PD) of capillaries (C) and endotheliocytes (E) were determined in pinnal dermis of C57BL mice before and after trauma. Moving (and overall) least-squares spectra before trauma detected in EPD (versus CPD) pronounced 3.5-day (circasemiseptan) and 8-h oscillations corresponding to components of the endothelin-1 chronome in human blood plasma reported earlier. Circadians were more pronounced in CPD. After trauma, circasemiseptan oscillations appeared also in CPD; their period gradually shortened and in two weeks split into about 2.5- and about 4.5-day oscillations; and circadian components became very pronounced. The pre-traumatic chronome was not restored within three weeks following trauma.

Animals↗
PubMed2001

Structural consequences of site-directed mutagenesis in flexible protein domains: NMR characterization of the L(55,56)S mutant of RhoGDI.

The guanine dissociation inhibitor RhoGDI consists of a folded C-terminal domain and a highly flexible N-terminal region, both of which are essential for biological activity, that is, inhibition of GDP dissociation from Rho GTPases, and regulation of their partitioning between membrane and cytosol. It was shown previously that the double mutation L55S/L56S in the flexible region of RhoGDI drastically decreases its affinity for Rac1. In the present work we study the effect of this double mutation on the conformational and dynamic properties of RhoGDI, and describe the weak interaction of the mutant with Rac1 using chemical shift mapping. We show that the helical content of the region 45-56 of RhoGDI is greatly reduced upon mutation, thus increasing the entropic penalty for the immobilization of the helix, and contributing to the loss of binding. In contrast to wild-type RhoGDI, no interaction with Rac1 could be identified for amino-acid residues of the flexible domain of the mutant RhoGDI and only very weak binding was observed for the folded domain of the mutant. The origins of the effect of the L55S/L56S mutation on the binding constant (decreased by at least three orders of magnitude relative to wild-type) are discussed with particular reference to the flexibility of this part of the protein.

Cell Membrane↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2001

Overuse injuries in youth sports: biomechanical considerations.

Many children today participate in highly organized sports programs that involve regimented year-round repetitive training. This type of training has led to an increased incidence of overuse musculoskeletal injuries. Sports physicians have dealt with sports injuries in children for many years and, on the basis of their clinical experience, have developed guidelines to treat and to try and prevent these injuries. The purpose of this article is to provide a biomechanical perspective of sports injuries in young athletes and blend ideas from this perspective with more traditional clinical perspectives that dominate the literature relative to this topic. Basic tissue and gross movement mechanics principles are used to identify growth, morphological, and movement factors that may predispose a child to an overuse injury. Several biomechanical analyses of simple movement tasks are presented to quantify the forces developed in various tissues and to illustrate the effects that growth can have on these forces. Guidelines are given for developing injury prediction models that may be used in the future to establish safe and effective training guidelines for children.

Adolescent↗
PubMed2001

Comparison of multidimensional flow cytometry with standard morphology for evaluation of early marrow response in pediatric acute lymphoblastic leukemia.

PURPOSE: We compared multidimensional flow cytometry (MDF) with morphology in evaluating early marrow response to induction chemotherapy in pediatric ALL. METHODS: Chemotherapy response was determined by standard morphology or by MDF assessed by residual leukemic cell percentage remaining in the marrow on days 7, 14, and 28 of induction. Bone marrow response was classified as M3 (>25% leukemic blasts) or M1/M2 (< or = 25% leukemic blasts). Multidimensional flow cytometry evaluation was compared with that of standard morphology. Available day-7 and day-14 marrow slides were also reevaluated by a single pathologist without patients' clinical information. RESULTS: Of 46 day-7 specimens, eight (17%) had discordant MDF and morphologic results (P < 0.001), including six classified as M3 by morphology but were M1/M2 by MDF, and two were classified as M3 by MDF but were M1/M2 by morphology. Of 24 day-14 bone marrow specimens, five (20.5%) were discordant (P < 0.001), including two classified as M3 by morphology but were M1/M2 by MDF, and three were classified as M3 by MDF but were M1/M2 by morphology. Reevaluation of the blinded day-7 and day-14 marrow slides yielded discordance between repeated pathology readings of 11% (P < 0.001) and 6% (P = 0.04), respectively. CONCLUSION: Our data show significant discordance between the morphologic and MDF evaluation of early marrow response. Early response to therapy is a significant prognostic indicator in pediatric acute lymphoblastic leukemia and is used to alter subsequent treatment; thus, precise assessment of response is important. A larger comparison of MDF with morphology for the evaluation of early response, including correlation with clinical outcome, is warranted.

Adolescent↗
PubMed2001

Serum amylase and lipase elevation is associated with intracranial events.

Serum amylase and lipase elevation has been observed in trauma patients and patients with traumatic intracranial bleeding. However, the causes of this elevation have not been clearly elucidated. A further question remains as to whether other intracranial events are associated with such enzyme elevation as well. We retrospectively reviewed 75 patients consecutively admitted to Cook County Hospital Neurosurgical Intensive Care Unit over a 3-month period for trauma, infection, tumor, or other space-occupying lesions with an unstable condition or neurological deficit. Eleven patients (15%) had elevated amylase and lipase levels. The patients were divided into two groups: Group I (n = 64) had normal and Group II (n = 11) had raised amylase and lipase levels [amylase 402 +/- 444 U/L with normal < or = 125 U/L and lipase 474 +/- 313 U/L with normal < or = 55 U/L]. All Group II patients suffered an intracranial event. Twenty-four Group I (38%) and 10 Group II (91%) patients required craniotomy (P < 0.01). No patients had clinical or radiographic evidence of pancreatitis. In summary, intracranial events are associated with serum amylase and lipase elevation probably through centrally activated pathways. Because of the lack of diagnostic value, routine pancreatic enzyme monitoring should not be performed in this patient population.

Aged↗
PubMed2000

Circumcision and genital dermatoses.

CONTEXT: It is well recognized that the presence of a foreskin predisposes to penile carcinoma and sexually transmitted infections. We have investigated the relationship between the presence or absence of the foreskin and penile dermatoses. OBJECTIVE: To determine whether there is an association between circumcision and penile dermatoses. DESIGN: A retrospective case control study of patients attending the department of dermatology with genital skin conditions. SUBJECTS: The study population consisted of 357 male patients referred for diagnosis and management of genital skin disease. The control population consisted of 305 male patients without genital skin disease attending the general dermatology clinics over a 4-month period. MAIN OUTCOME MEASURES: The relationship between circumcision and the presence or absence of skin disease involving the penis was investigated. The rate of circumcision in the general male dermatology population was determined. RESULTS: The most common diagnoses were psoriasis (n = 94), penile infections (n = 58), lichen sclerosus (n = 52), lichen planus (n = 39), seborrheic dermatitis (n = 29), and Zoon balanitis (n = 27). Less common diagnoses included squamous cell carcinoma (n = 4), bowenoid papulosis (n = 3), and Bowen disease (n = 3). The age-adjusted odds ratio for all penile skin diseases associated with presence of the foreskin was 3.24 (95% confidence interval, 2.26-4.64). All patients with Zoon balanitis, bowenoid papulosis, and nonspecific balanoposthitis were uncircumcised. Lichen sclerosus was diagnosed in only 1 circumcised patient. Most patients with psoriasis, lichen planus, and seborrheic eczema (72%, 69%, and 72%, respectively) were uncircumcised at presentation. The majority of men with penile infections (84%) were uncircumcised. CONCLUSIONS: Most cases of inflammatory dermatoses were diagnosed in uncircumcised men, suggesting that circumcision protects against inflammatory dermatoses. The presence of the foreskin may promote inflammation by a köebnerization phenomenon, or the presence of infectious agents, as yet unidentified, may induce inflammation. The data suggest that circumcision prevents or protects against common infective penile dermatoses.

Adolescent↗
PubMed2000

Very intensive, short-term chemotherapy for children and adolescents with metastatic sarcomas.

BACKGROUND: To improve the prognosis for pediatric patients with metastatic sarcomas, including the Ewing sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS), and undifferentiated sarcoma (UDS), we tested the feasibility of a brief, intensive regimen of chemotherapy that maximizes dose intensity. PROCEDURE: Twenty-four children and adolescents with metastatic sarcomas received VACIME chemotherapy, consisting of eight courses of vincristine 2 mg/m(2) on day 0; doxorubicin 20 mg/m(2)/day on days 0-3; cyclophosphamide 360 mg/m(2)/day on days 0-4; ifosfamide 1,800 mg/m(2)/day on days 0-4; mesna 2,400 mg/m(2)/day; and etoposide 100 mg/m(2)/day on days 0-4. Doxorubicin was omitted in courses 7 and 8. Granulocyte colony-stimulating factor (G-CSF) was used routinely following each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery and resolution of nonhematopoietic toxicities permitted. Surgical resection followed course 6, and radiotherapy followed the completion of all therapy. RESULTS: Thirteen patients achieved a complete response (CR) with chemotherapy alone, and seven more achieved a CR following surgical resection after course 6 (overall CR rate 83%). There was one toxic death. Thirteen patients developed progressive disease, with 2- and 4-year event-free survivals (95% confidence interval) of 50% (30-70%) and 45% (25-65%), respectively. Myelosuppression was severe and cumulative, leading to dose reductions and chemotherapy interval delays. Mucositis was the most common nonhematopoietic toxicity. CONCLUSIONS: VACIME chemotherapy was a feasible dose-intensive regimen for pediatric patients with metastatic sarcomas. Cumulative hematopoietic toxicity and severe mucositis limited the delivery of chemotherapy as prescribed. The CR and 2-year event-free survival rates were superior to those of most previously reported regimens.

Adolescent↗
PubMed2000

Busulfan, melphalan, and thiotepa with or without total marrow irradiation with hematopoietic stem cell rescue for poor-risk Ewing-Sarcoma-Family tumors.

BACKGROUND: Survival following metastatic or recurrent Ewing sarcoma family tumors (ESFT) remains <25%. Myeloablative therapy with hematopoietic stem cell transplantation (HSCT) may improve survival for poor-risk ESFT. We describe the toxicity and efficacy of a myeloablative chemotherapy regimen, followed by a second myeloablative radiotherapy regimen as consolidation treatment for poor-risk ESFT. PROCEDURE: Sixteen patients with poor-risk ESFT were treated with myeloablative therapy followed by HSCT. All patients received busulfan, melphalan, and thiotepa (BuMelTT) as chemotherapy conditioning. Nine patients received total marrow irradiation (TMI) as a second myeloablative therapy, also followed by HSCT. Seven patients were excluded from TMI because of inadequate peripheral blood stem cell harvest, extensive prior radiation therapy, early disease progression, orpatient refusal. The disease status prior to my eloablative therapy was first complete response (CR1) in three patients, CR2 in nine, second partial response (PR2) in one, CR3 in one, and progressive disease (PD) in two. RESULTS: One patient died of regimen-related toxicity, one from late pulmonary toxicity, and one following allogeneic transplantation for myelodysplasia. Eight developed recurrent disease (median time to progression 6.8 months). Six survive without relapse from 27 to 66 months following BuMelTT (median follow-up 42 months), all of whom received both BuMelTT and TMI patients (3-year event-free survival 36%). CONCLUSIONS: Dual myeloablative therapy with BuMelTT and TMI was a feasible and promising treatment approach for patients with poor-risk ESFT. Inability to collect sufficient PBSC and extensive previous radiation therapy limit the ability to deliver TMI as a second HSCT conditioning regimen.

Adolescent↗
PubMed2000

Phase I topotecan preparative regimen for high-risk neuroblastoma, high-grade glioma, and refractory/recurrent pediatric solid tumors.

We evaluated the toxicity and maximum tolerated dose of topotecan in a novel myeloablative regimen as treatment for high-risk pediatric tumors. Patients received an assigned topotecan dosage in combination with fixed doses of carboplatin and thiotepa, followed by autologous hematopoietic stem cells infusion. Topotecan dose was escalated in cohorts of four patients until the maximum tolerated dose of topotecan was defined or until accrual of 30 patients. Pharmacokinetics of topotecan were examined, and event-free survival was estimated. We describe preliminary results following treatment of 25 pediatric patients with high-risk solid tumors.

Antineoplastic Agents↗
PubMed2000

A new instrumentation system for training rowers.

A dry-land rowing system was developed to provide the coach and/or athlete with quantitative information about the athlete's kinetics and kinematics while the athlete trains. This system consists of a Concept II rowing ergometer instrumented with a force transducer and potentiometer, four electrogoniometers attached to the athlete's ankle, knee, hip, and elbow, and a data acquisition computer. The force transducer is used to quantify the athlete's pulling force. The potentiometer signal is used to locate the position of the handle. The electrogoniometers provide signals proportional to joint angles. A link segment model of the human body is used to locate joint centers based on limb lengths and joint angles. The computer is used to collect and process all the transducer signals, perform the link segment calculations and provide feedback to the coach or athlete in the form of a stick figure animation overlaid with kinematic and kinetic information. This system allows the coach and athlete to quickly study a rower's mechanics, to evaluate the effects that technique changes have on the power produced by the athlete, and to identify technique differences between athletes.

Biomechanical Phenomena↗
PubMed2000

Hypocaloric parenteral nutrition support in elderly obese patients.

Hypocaloric nutritional support has been successfully used to achieve positive nitrogen balance in obese patients. However, advanced age is associated with changes in substrate metabolism. To evaluate the efficacy of this practice in elderly patients, we retrospectively reviewed 30 obese patients requiring parenteral nutrition support. Total caloric requirements (TCR) were calculated on the basis of the Harris-Benedict equation. Patients were given a minimum of 1.5 g/kg/day protein, 75 per cent of TCR when current body weight was >120 and < or =150 per cent of ideal body weight (IBW), and 60 per cent of TCR if current body weight was >150 per cent of IBW. The patients were divided into two groups: Group I (N = 18) patients were age <60 and Group II (N = 12) patients were > or =60 years of age. Only one of the Group I patients (143.2 +/- 25.7% IBW, received 18.2 +/- 3.7 kcal/kg/day and 1.6 +/- 0.4 g/kg/day protein), but five of the Group II patients (141.3 +/- 14.4% IBW, received 18.3 +/- 2.6 kcal/kg/day and 1.7 +/- 0.3 g/kg/day protein), had negative nitrogen balance (P = 0.025). Apparently, elderly obese patients have limited capacity to mobilize their fat stores as energy sources and may continue to undergo protein catabolism with hypocaloric high-protein nutrition support. Therefore, this form of nutritional support should be used with caution in elderly obese patients.

Adult↗