Biomedical subjects

K M Kelly

Publications and source records attributed to K M Kelly.

At least 19 recordsLinked to original sources

PubMed1999

Cryogen spray cooling in combination with nonablative laser treatment of facial rhytides.

BACKGROUND: Cryogen spray cooling can be used to provide epidermal protection while still achieving spatially selective photocoagulation in the upper dermis. The objective of this study is to determine the efficacy and safety of cryogen spray cooling in combination with a nonablative Nd:YAG (lambda = 1320 nm) laser treatment of facial rhytides in human volunteers. OBSERVATIONS: Thirty-five adults with bilateral periorbital rhytides were treated with cryogen spray cooling in combination with 3 nonablative laser treatments performed sequentially at intervals of 2 weeks. Small but statistically significant improvements were noted in the mild, moderate, and severe rhytid groups 12 weeks after the final laser treatment. A final assessment performed 24 weeks after the last treatment showed statistically significant improvement only in the severe rhytid group. The procedure was found to be safe; 4 sites (5.6%) developed transient hyperpigmentation. Two sites (2.8%) subsequently developed barely perceptible pinpoint pitted scars. CONCLUSIONS: Cryogen spray cooling is a safe and effective method for protecting the epidermis during nonablative laser treatment of facial rhytides thereby avoiding much of the morbidity associated with other resurfacing procedures. Minor improvements in rhytides can be achieved with the current technology. Optimization of treatment parameters may further improve these results.

Adult↗

PubMed1999

Q-switched ruby laser treatment of a congenital melanocytic nevus.

BACKGROUND: The treatment of medium-sized (1.5-20 cm diameter) congenital melanocytic nevi (CMN) has been the concern of dermatologists for decades. Although many techniques have been described and utilized, no single treatment has emerged as applicable under all circumstances. METHODS: The Q-switched ruby laser (QSRL) at 694 nm, a wavelength well absorbed by melanin relative to other optically absorbing structures in skin, causes highly selective destruction of pigment-laden cells. In addition, the 20-nanosecond pulse duration produced by this laser approximates the thermal relaxation time for melanosomes, thereby confining the energy to the targeted cells. RESULTS: In the present report, treatment using the QSRL resulted in complete clinical removal of a biopsy-documented medium-sized compound CMN with no recurrence after 5 years. In contrast to other therapeutic modalities, complications such has hypertrophic scarring, dyspigmentation, or atrophy were not observed.

Facial Neoplasms↗

PubMed1999

Cranial growth unrestricted during treatment of deformational plagiocephaly.

OBJECTIVES: The Dynamic Orthotic Cranioplasty (DOC) Band(TM) is a cranial orthosis used to treat deformational plagiocephaly. The ability of this device to redirect growth and thus, improve craniofacial asymmetry has raised concerns regarding the potential restriction of cranial growth. The purpose of this study was to evaluate the growth of the head during correction of plagiocephaly. METHODS: The study sample consisted of 190 children: 81 females (42. 6%) and 109 males (57.4%) All patients had been diagnosed with nonsynostotic plagiocephaly, did not have other significant medical conditions, were compliant with DOC protocol, and had complete anthropometric measurements at entrance and exit from treatment. Growth of the head was evaluated using head circumference, maximum cranial width and maximum cranial length. Correction of plagiocephaly was evaluated by documenting the reduction of craniofacial asymmetry of the cranial vault, skull base and face. Paired t tests were used to assess the significance of changes in these anthropometric measurements. Differences were considered significant if p < 0.05. RESULTS: Average entrance age was 6.5 months with a mean treatment time of 4.1 months. Statistical analysis demonstrated highly significant reductions in asymmetry in all three regions (p < 0.001). More importantly, these corrections were achieved with synchronous growth of the skull as demonstrated by highly significant increases (p < 0.001) in head circumference, maximum cranial width and maximum cranial length. CONCLUSIONS: These findings document statistically significant increases in cranial growth in association with concomitant reductions of the cranial asymmetries associated with deformational plagiocephaly.

Cephalometry↗

PubMed1999

Multiple-birth infants at higher risk for development of deformational plagiocephaly.

OBJECTIVE: Deformational plagiocephaly refers to the development of an abnormal head shape in infants resulting from externally applied molding forces, which may occur either prenatally or postnatally. We have observed that an unexpectedly high number of multiple-birth infants have presented to our center with this condition. The purposes of this investigation were to: 1) determine the significance of this observation; and 2) examine the risk factors that may make this population more susceptible to the development of plagiocephaly. MATERIALS AND METHODS: A retrospective review of our database was performed to identify those infants who were of multiple-birth origin. The parents of these infants were contacted by phone to complete a survey regarding the prenatal and postnatal history of their child. Similar information was obtained for the state of Arizona from the Office of Vital Statistics. A chi2 analysis was used to compare the incidence of multiple births in Arizona with the incidence of multiple births in our treatment population. RESULTS: Between 1993 and 1996, 69 (8.6%) of the 801 infants treated for deformational plagiocephaly at our Phoenix center were of multiple-birth origin. Four infants who had been treated postoperatively after surgery for craniosynostosis, as well as 5 patients who had been referred from out of state, were excluded from further study. The chi2 analysis of the remaining 60 patients confirmed that a statistically significant number of plural-birth infants had presented with deformational plagiocephaly. Four risk factors were identified as having occurred at high frequency in this population: in utero constraint, supine sleeping position, torticollis, and prematurity. CONCLUSIONS: The current findings of this investigation confirm that a significant number of multiple-birth infants have presented to our clinic with deformational plagiocephaly. Compared with their singleton counterparts, plural infants seem to be at higher risk for the development of deformational plagiocephaly, because they are more likely to be exposed to multiple risk factors.deformational plagiocephaly, multiple birth, plurality.

Female↗

PubMed1999

Importance of early recognition and treatment of deformational plagiocephaly with orthotic cranioplasty.

OBJECTIVES: Infants with positional plagiocephaly often exhibit complex multistructural asymmetries that affect the face and skull base as well as the cranial vault. Dynamic Orthotic Cranioplasty (DOC) was developed as a nonsurgical alternative for the treatment of positional plagiocephaly. The effectiveness of DOC has been discussed elsewhere. The purpose of this study was to assess the influence of factors such as entrance age, treatment time, and initial severity on the effectiveness of correction. METHODS: The study sample consisted of 258 children with cranial vault asymmetry (CVA) treated prior to 1 year of age. In addition, 246 patients (92%) exhibited concurrent skull base (SBA) and orbitotragial depth (OTDA) asymmetries. All patients had been diagnosed with nonsynostotic plagiocephaly, did not have other contributing medical conditions, were compliant with DOC protocol, and had complete anthropometric measurements at entrance and exit from treatment. RESULTS: Mean age at start of treatment was 6.5 (+/-1.9) months (range, 2.8 to 11.0 months), with an average treatment time of 4.1 (+/-2.2) months. The effects of the treatment variables were analyzed using three-way analysis of variance. As expected, initial severity was significantly associated with the amount of correction (p = .0001). However, treatment time was not significant (p > .05). Most importantly, the analysis revealed that, having accounted for initial severity, entrance age had a statistically significant effect [F(1,254) = 8.36, p = .0042] on the correction of CVA. Similar results were identified for both the SBA [F(1,254) = 5.53, p = .0195] and the OTDA [F(1,254) = 5.22, p = .0231] asymmetries. CONCLUSIONS: These findings support clinical observations that earlier intervention results in significantly improved treatment of plagiocephaly, independent of the severity of the presenting asymmetries.

Analysis of Variance↗

PubMed1998

t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.

We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis in both cases showed two identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detectable in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested t(11;22)(q23;q11. 2) disrupting MLL. Known 5' sequence from MLL but unknown 3' sequence from chromosome band 22q11.2 formed the breakpoint junction on the der(11) chromosome. We used panhandle variant PCR to clone the translocation breakpoint. By ligating a single-stranded oligonucleotide that was homologous to known 5' MLL genomic sequence to the 5' ends of BamHI-digested DNA through a bridging oligonucleotide, we formed the stem-loop template for panhandle variant PCR which yielded products of 3.9 kb. The MLL genomic breakpoint was in intron 7. The sequence of the partner DNA from band 22q11.2 was identical to the hCDCrel (human cell division cycle related) gene that maps to the region commonly deleted in DiGeorge and velocardiofacial syndromes. Both MLL and hCDCrel contained homologous CT, TTTGTG, and GAA sequences within a few base pairs of their respective breakpoints, which may have been important in uniting these two genes by translocation. Reverse transcriptase-PCR amplified an in-frame fusion of MLL exon 7 to hCDCrel exon 3, indicating that an MLL-hCDCrel chimeric mRNA had been transcribed. Panhandle variant PCR is a powerful strategy for cloning translocation breakpoints where the partner gene is undetermined. This application of the method identified a region of chromosome band 22q11.2 involved in both leukemia and a constitutional disorder.

Abnormalities, Multiple↗

PubMed1998

Gabapentin. Antiepileptic mechanism of action.

Gabapentin is an antiepileptic drug used in the treatment of partial and generalized tonic-clonic seizures. Its antiepileptic mechanism of action is not known. The transport of gabapentin across membranes and its demonstrated effects on voltage-gated ion channels (sodium, calcium), presynaptic mechanisms that can enhance GABAergic inhibition, and ligand-gated ion channels (GABA receptors and glutamate receptors) are reviewed.

Acetates↗

PubMed1998

The relationship between gait parameters and pain in persons with transtibial amputation: a preliminary report.

This is a preliminary study of the potential relationship between pain and gait parameters in 11 persons with transtibial amputation who underwent gait analysis under both baseline and discomfort walking conditions. Gait analysis included measurement with a VA-Rancho Stride Analyzer of the following gait parameters: velocity, cadence, stride length, gait cycle, and support time. These data were correlated with pain intensity data determined with a standard Visual Analog Scale. Wide ranges of discomfort were reported and corresponding alterations in gait parameters varied greatly in both magnitude and quality. There was no obvious pattern in acclimation to discomfort. A significant correlation was found between pain intensity and the magnitude of change in velocity (p < 0.05). In addition, all subjects reporting significant pain (> 33% of maximum) slowed down, while gait alterations of others varied widely in response to the experience of pain. Further studies with a larger and more homogeneous subject pool to examine these relationships fully are recommended to follow this preliminary report.

Aged↗

PubMed1998

Ultrasound characteristics of breast carcinoma.

Recent advances in ultrasound technology, such as the use of high-frequency linear transducers, color flow Doppler, and computer-enhanced imaging, have improved the diagnostic utility of ultrasound. The following retrospective study was performed to evaluate the efficacy of sonographic signs of malignancy and to compare sonography to mammography in 157 patients with palpable, biopsy-proven breast carcinomas. The mammogram reports and sonograms were all reviewed. The grade of each mammogram was recorded using the American College of Radiology mammogram grading scale. All sonograms were reviewed and assigned a score using an adaptation of this scale. Of 157 lesions, 121 were read as suspicious or probable malignancies on mammogram. Thirty-three lesions were read as benign or normal on mammogram. Three patients did not receive mammograms. All 157 lesions were read as either suspicious or probably malignant on ultrasound. Using the 16 described criteria, high-definition sonography complements mammography and appears to be a sensitive modality in the evaluation of palpable biopsy-proven breast malignancies. The diagnostic utility of ultrasound will likely be most important in the evaluation of nonpalpable breast masses; however, a prospective randomized trial will need to be performed.

Biopsy↗

PubMed1997

Video-assisted thoracic surgery: has technology found its place?

BACKGROUND: Since the introduction of minimally invasive surgical techniques in thoracic surgery in 1990, video-assisted thoracic surgery (VATS) has become the approach for many thoracic operations. The role of VATS has slowly evolved but has not been clearly defined. To better understand the role of VATS, we undertook a survey of practicing thoracic surgeons. METHODS: A questionnaire was sent to members of the General Thoracic Surgery Club asking the role of VATS in their practice and their opinions regarding appropriate applications, advantages, and limitations of the approach. RESULTS: Two hundred of the 229 members (87.3%) responded to the questionnaire. In this largely academic (66.3%) group of thoracic surgeons, 72% of whom had more than 10 years experience in general thoracic surgery, VATS was the preferred approach (> 50% response) for the management of pleural disease, lung biopsy, recurrent pneumothorax, and sympathectomy. A majority of respondents thought that VATS was an acceptable approach for the diagnosis of the indeterminate pulmonary nodule and of anterior and posterior mediastinal masses, and for the management of early empyema, clotted hemothoraces, secondary pneumothorax, limited lung cancer treatment, and benign esophageal disease. Video-assisted thoracic surgery was thought to be unacceptable or investigational by a majority for thymectomy, lobectomy, and lung volume reduction operations. Video-assisted thoracic surgery still represents only a small portion of the thoracic procedures performed, but there is a gradual increase in its rate of use, although 38.1% expressed concern regarding overuse. The main limitation was thought to be in the management of oncologic disease. CONCLUSIONS: It appears that VATS is a valuable addition to the practice of thoracic surgery, but significant limitations exist. Although there appear to be many specific indications defined, there is still a significant evolutionary component.

Attitude of Health Personnel↗

PubMed1997

Superior in vivo response of recombinant factor VIII concentrate in children with hemophilia A.

OBJECTIVE: Our previous experience with highly purified plasma-derived factor VIII (pdFVIII) concentrates showed that adult dosage recommendations were not applicable to children. In this study, we compared the in vivo response and recovery of recombinant factor VIII (rFVIII) with those of highly purified pdFVIII concentrate in children with hemophilia A. STUDY DESIGN: Ten boys with severe factor VIII deficiency and no concurrent bleeding episodes participated in a masked, prospective, crossover study comparing factor VIII coagulant activity after infusion of 50 units of pdFVIII and rFVIII products per kilogram of body weight. RESULTS: Mean peak factor VIII response with rFVIII was 1.91% +/- 0.14%, significantly better than the response observed with highly purified pdFVIII of 1.5% +/- 0.15% (p = 0.007). Mean peak factor VIII recovery was 100.5% with rFVIII versus 78.7% with pdFVIII (p = 0.007). Positive correlations between response to rFVIII and body surface area (r = 0.734, p = 0.015), body weight (r = 0.762, p = 0.01), and plasma volume (r = 0.659, p = 0.03) were observed. CONCLUSIONS: Infusion of rFVIII produced a significantly better response and recovery in vivo than infusion of highly purified pdFVIII in children. The response in children after infusion of rFVIII was similar to the response previously observed in adults.

Adult↗

PubMed1997

Oncologic emergencies.

The prognosis for the child with cancer has improved dramatically over the past decades. With this success comes the need for recognition and proper treatment of emergencies. Respiratory or circulatory failure may arise from compression of the SVC or airway. Epidural spinal cord compression by tumor may lead to irreversible paraplegia or urinary incontinence if intervention is not rapid. Raised intracranial pressure may be a life-threatening presentation of a brain tumor. Bone marrow failure, with anemia and thrombocytopenia, is associated with malignant infiltration of the marrow. Hyperleukocytosis carries a high risk of thrombotic events if not treated promptly. Coagulation abnormalities are seen in many childhood cancers at the time of diagnosis. Life-threatening metabolic abnormalities are observed at presentation in children with leukemia and lymphoma. Hypercalcemia, although rare, may be a difficult situation to correct. Immediate attention to these emergencies and appropriate treatment may save the life of a child with cancer or make his or her subsequent course just a little smoother.

Algorithms↗

PubMed1997

Common and variant gene fusions predict distinct clinical phenotypes in rhabdomyosarcoma.

PURPOSE: We evaluated the clinical features of the common PAX3-FKHR and variant PAX7-FKHR gene fusions observed in rhabdomyosarcoma. PATIENTS AND METHODS: Reverse-transcriptase polymerase chain reaction (RT-PCR) assays were used to detect the gene fusions in 34 cases of rhabdomyosarcoma. Clinical data were obtained retrospectively and compared with the molecular results. RESULTS: The PAX3-FKHR and PAX7-FKHR gene fusions were present in tumors from 18 and 16 patients, respectively. The group with a PAX7-FKHR fusion was younger (P = .01) and presented more often with an extremity lesion (82% v 22%; P = .001). PAX7-FKHR tumors were more often localized than PAX3-FKHR tumors (P = .03). In patients with metastatic disease at diagnosis, the patterns were different: PAX7-FKHR patients had metastatic disease that involved only bone (n = 2) and distant nodes (n = 2), while the PAX3-FKHR group had multiple sites involved, including bone (n = 7), marrow (n = 7), lungs (n = 3), distant nodes (n = 2), skin (n = 1), and brain (n = 1). No significant difference in relapse rate was observed. A trend toward improved overall survival in the PAX7-FKHR group was noted (P = .09). Event-free survival for this PAX7-FKHR group was significantly longer (P = .04). CONCLUSION: Our results suggest that the common PAX3-FKHR and the variant PAX7-FKHR fusions are associated with distinct clinical phenotypes. Identification of fusion gene status may be a useful diagnostic tool in rhabdomyosarcoma.

Adolescent↗

PubMed1997

Hb Osler [beta 145(HC2)Tyr-->Asp] results from posttranslational modification.

We studied two members of an African American family with erythrocytosis. An abnormal hemoglobin variant with an electrophoretic pattern on cellulose acetate similar to Hb J was identified. The oxygen dissociation curve using whole blood was biphasic, dramatically left-shifted, and hyperbolic. Sequence analysis of DNA from the proband showed heterozygosity for a T-->A change at the first position of codon 145 in the beta-globin gene which results in the substitution of an asparagine residue for normal tyrosine. The second cycle of C-terminal amino acid sequence analysis of a mixture of alpha- and beta-globin chains showed tyrosine, aspartic acid, and small amounts of asparagine. Collectively, these results indicate the existence of a mutation at codon 145 of the beta-globin gene which encodes for asparagine instead of tyrosine, and that asparagine then undergoes a partial posttranslational deamidation to aspartic acid. This amino acid substitution corresponds to Hb Osler, which is a high oxygen affinity hemoglobin variant, initially described to be caused by a substitution of Tyr-->Asp at beta 145. Posttranslational amino acid modification may constitute an important component in the pathophysiology of hemoglobinopathies.

Adult↗

PubMed1996

Minimal disease detection in patients with alveolar rhabdomyosarcoma using a reverse transcriptase-polymerase chain reaction method.

BACKGROUND: Polymerase chain reaction (PCR) assays that detect fusion genes resulting from consistent chromosomal translocations have been used to detect minimal residual disease, primarily in hematologic malignancies. Molecular assays have been developed recently that detect the PAX3-FKHR or PAX7-FKHR fusion transcript resulting from the t(2; 13) or t(1; 13) translocation consistently observed in alveolar rhabdomyosarcoma. Because of the tumor's propensity to disseminate widely, our aim was to determine whether or not reverse transcriptase-PCR assays could detect submicroscopic disease in bone marrow or peripheral blood specimens. METHODS: We analyzed 19 bone marrow samples from 11 patients with a known gene fusion in their primary tumor. Specimens were collected at diagnosis, remission, and relapse. Fourteen peripheral blood samples were obtained serially from 5 of these patients. A reverse transcriptase-PCR assay was used to detect the presence of the PAX3-FKHR or PAX7-FKHR fusion transcript. These results were compared with the results of microscopic examination of the bone marrow. Medical records of all 11 patients were reviewed. RESULTS: Adequate amplifiable RNA was obtained in 17 of 19 marrow samples. The PCR assay detected fusion products in all 4 specimens obtained from 3 patients with histologic evidence of bone marrow involvement. In addition, PAX3-FKHR fusion products were detected in bone marrows from 2 patients for whom there was no histologic evidence of disease. The fusion transcripts were not detected in any of the peripheral blood samples. CONCLUSIONS: The detection of submicroscopic disease is possible in alveolar rhabdomyosarcoma patients using PCR. These assays may have a role in staging, monitoring therapy, purging protocols for autologous bone marrow transplantation, and post therapy follow-up. Larger prospective studies are needed to address the clinical relevance of these results.

Bone Marrow↗

PubMed1996

IGHG3 G and the pathogenesis of hyperreactive malarious splenomegaly.

Hyperreactive malarious splenomegaly is an aberrant response to chronic malarial infection, defined by persistent gross splenomegaly and elevated serum IgM and IgG. The populational and familial patterns of this disorder suggest genetically based, immune incompetence. In Papua New Guinea, the disease occurs among populations characterized by high frequencies of IGHG3 G haplotypes. Elsewhere, the distribution and prevalence of hyperreactive malarious splenomegaly is consistent with the distributions of IGHG3 alleles. Drawing upon this relationship, I suggest that expression of the G3M G phenotype is a necessary precondition for hyperreactive malarious splenomegaly, consistent with the pathogenesis of malaria and the functions of the immune system.

Antigen-Antibody Complex↗

PubMed1996

Does increasing oxygen delivery improve outcome? Yes.

Increasing DO2 to supranormal levels, spontaneously or therapeutically, correlates with better survival in the critically ill patient, but not all patients who attain a DO2I greater than 600 mL/min/m2 survive. Conversely, there is often a 50% or greater survival rate in patients who do not reach normal DO2I values. No investigator has been able to show an incremental increase in survival with increasing DO2I; but studies have shown improved survival rates with increasing SVO2. The observations support the idea that absolute values for DO2I are not as important as the ability to normalize SVO2 when SVO2 is low. Therapeutic interventions may be most effective in those patients demonstrating increased peripheral oxygen extraction (SVO2 = 40% to 60%). These "type A" patients are mounting an appropriate response to increased needs. Several authors have noted increased mortality rates for patients unable to increase a low VO2 despite increased DO2. This is McClave's "type B" physiologic response. Flow dependency is not correlated with mortality. In fact, it is the patient who can raise VO2 when DO2 is increased who tends to survive. Dantzker, Giunta, and Hotchkiss propose that the flow dependency of VO2 may be a normal physiologic response. Clinical outcomes continue to support the necessity of maintaining an optimal DO2 in critically ill patients. The question of what is optimal DO2 has yet to be answered. Vincent nicely summaries the present "state of the art" in treating the critically ill: "Rather than aim at achieving arbitrary target values in all patients, we believe that this process should be based on a careful clinical evaluation of the individual patient, complemented by measurements of cardiac output, determinations of mixed venous oxygen saturation (or the oxygen-extraction ratio), and other measurements of tissue perfusion, such as the base deficit, blood lactate level, or gastric intramucosal pH." In addition, the type or stage of physiologic response should be identified. Independent markers of tissue ischemia should be sought and abnormalities corrected by increasing DO2. SVO2 should be normalized when low, again by increasing DO2. Data continue to support clinical interventions aimed at optimizing DO2. Does increasing DO2 increase the survival rates of critically ill patients? Sometimes.

Critical Care↗

PubMed1996

Sonographic evaluation of benign and malignant breast lesions.

Sonography can be used for the accurate differentiation of many benign and malignant solid breast lesions. However, considerable experience, and close correlation with the physical examination and the mammogram, are required to do so. Sixteen sonographic signs useful in this differentiation are reviewed. The specific sonographic appearances of the most common being entities are described. Primary breast malignancies are divided into five categories according to their sonographic presentations: (1) classic neoplasms with irregular borders, echoic rims, and usually posterior shadowing, (2) small, round neoplasms with no echoic rim or posterior shadowing, (3) neoplasms with mixed or increased echogenicity, (4) cystic or intracystic carcinomas, and (5) colloid carcinomas. Methods for identification of these different types of invasive malignancy, and of in situ carcinomas, are presented. The usefulness of sonomammography is considered in specific circumstances, including evaluation of mammographic or physical findings, dense breasts, post-radiation breasts, and women under 35 years of age.

Breast Diseases↗