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Biomedical subjects

J L Haynes

Publications and source records attributed to J L Haynes.

At least 19 recordsLinked to original sources

Chiral separation with dipeptide-terminated polymeric surfactants: the effect of an extra heteroatom on the polar head group.

Chiral recognition of two binaphthyl derivatives and three benzodiazepines were studied by use of polymeric surfactants in electrokinetic chromatography. Four specific dipeptide terminated (multichiral) micelle polymers were synthesized for this study. These include poly (sodium-N-undecanoyl-L-alanyl-leucinate)-(poly L-SUAL), poly (sodium-N-undecanoyl-L-valyl-leucinate) (poly L-SUVL), poly (sodium-N-undecanoyl-Lseryl-leucinate) (poly L-SUSL), and poly(sodium-N-undecanoyl-L-threonyl-leucinate) (poly L-SUTL). In addition to the chiral separation study, the physicochemical properties (critical micelle concentration and specific rotation) of each polymer were investigated. The molecular weights of the various dipeptide-terminated micelle polymers were determined using analytical ultracentrifugation. These dipeptide-terminated micelle polymers were designed to study the effect of the extra heteroatom at the polar head group of the micelle polymer (i.e., poly L-SUSL compared to poly L-SUAL and poly L-SUTL compared to poly L-SUVL) on the enantiomeric separation of the binaphthyl derivatives and benzodiazepines. The synergistic effect of three chiral centers (poly L-SUTL) provided improved resolution over that of two chiral centered dipeptide-terminated micelle polymer in the case of (+/-)-temazepam, (+/-)-oxazepam, (+/-)-binaphthol, and (+/-)-binaphthol phosphate. The chiral recognition mechanisms in these cases were additionally controlled by the presence of the extra heteroatom located on the polar head group of the micelle polymers.

Anti-Anxiety Agents↗

Nested cladistic analysis indicates population fragmentation shapes genetic diversity in a freshwater mussel.

Recently developed phylogeographic analyses that incorporate genealogical relationships of alleles offer the exciting prospect of disentangling historical from contemporary events. However, the relative advantages and shortfalls of this approach remain to be studied. We compared the nested cladistic method to the more traditional analysis of variance approach in a study of intraspecific genetic variation in the freshwater mussel, Lampsilis hydiana. We surveyed 257 specimens for nucleotide sequence level variation in a fragment of the mitochondrial 16S rRNA gene. When compared side by side, nested cladistic analysis and analysis of molecular variance (AMOVA) identified fragmentation of Arkansas river populations from remaining populations to the southwest. Nested cladistic analysis identified a second, more recent separation of Ouachita and Upper Saline river populations that was not detected by AMOVA. Differences among analytical methods probably arise from treatment of spatial hierarchical information: hierarchical groups emerge via a parsimony criterion in nested cladistic analysis but must be specified a priori in AMOVA. Both methods identified significant genetic structure among localities within hierarchical groups. Results from AMOVA suggested little gene flow among local populations with an island model. However, inferences about process that gave rise to patterns at this level were not possible in nested cladistic analysis, because an ancestral (interior) haplotype was not observed for a key one-step clade in the parsimony network. Our results suggest that, under some circumstances, nested cladistic analysis has lower power than more traditional analysis of variance to infer processes at the local population level.

Analysis of Variance↗

Cationic beta-cyclodextrin derivative for chiral separations.

A novel hepta-substituted beta-cyclodextrin bearing the methoxyethylamine group linked to the upper cyclodextrin rim was successfully used as a chiral selector for enantiomeric separation of non-steroidal anti-inflammatory drugs (NSAIDs) and phenoxypropionic acid herbicides (PPAHs). Separation parameters such as pH and concentration were found to have major influences on enantiomeric resolution of the NSAIDs and PPAHs. Results indicate that heptakis(6-methoxyethylamine-6-deoxy)-beta-cyclodextrin [beta-CD-OMe (VII)] performs exceptionally well for the enantiomeric resolution of NSAIDs: indoprofen and fenoprofen (Rs = 11 and 14, respectively). In addition, baseline enantiomeric separation of a mixture of six pairs of PPAHs was achieved in under 30 min. Compared to other cationic beta-cyclodextrins reported in the literature, the beta-CD-OMe (VII) showed improved selectivity for both classes of the aforementioned anionic racemates.

Anti-Inflammatory Agents, Non-Steroidal↗

A prospective evaluation of atherosclerotic risk factors and hypercoagulability in young adults with premature lower extremity atherosclerosis.

PURPOSE: Fifty-one consecutive patients with premature lower extremity atherosclerosis were prospectively evaluated for atherogenic risk factors and primary or acquired hypercoagulability, which might contribute to early ischemia and revascularization failure. METHODS: Laboratory tests included plasma assays of (1) natural anticoagulants (NAC), lipoprotein (a) (Lp[a]), and anticardiolipin antibodies, and (2) fibrinolytic activators and inhibitors at baseline and stimulated after 20 minutes of upper extremity venous occlusion. RESULTS: Forty-six (90%) of these 51 patients had laboratory abnormalities. One or more NAC deficiencies were found in 15 (30%) patients and included antithrombin III (n = 5), protein C (n = 8), protein S (n = 4), and heparin cofactor II (n = 2). Hypofibrinolysis was identified as a deficiency of stimulated tissue plasminogen activator in 22 (45%) patients and elevated plasminogen activator inhibitor-1 (PAI-1) in 29 (59%). Elevated Lp(a) was found in 43 (86%) patients. Five (10%) patients had anticardiolipin antibodies. Ten patients had combined NAC deficiency and hypofibrinolysis. Five (10%) patients had no abnormality. NAC deficiencies, especially protein C deficiency, were associated with acute ischemia (p < 0.01), prior vascular intervention (p < 0.01), an increasing number of total vascular procedures (p < 0.01), and major amputation (p < 0.01). PAI-1 was associated with a history of heart disease (p < 0.05) and prior vascular procedures (p < 0.05). Elevated Lp(a) was associated with elevated PAI-1 (p < 0.05). Retesting in 20 patients suggested that 80% of NAC deficiencies were acquired, but abnormalities persisted in 66% of patients with elevated PAI-1 and in 93% of those with elevated Lp(a). CONCLUSIONS: These data strongly support the hypothesis that the convergence of atherogenic risk factors and hypercoagulability play an important role in early ischemia and poor results reported for lower extremity vascular procedures in young adults.

Adult↗

Pneumococcal clearance function of the intact autotransplanted spleen.

OBJECTIVE: To determine if the venous drainage of the spleen into the portal circulation is essential for its ability to protect against encapsulated bacterial challenge. DESIGN AND INTERVENTIONS: Three groups of dogs were randomly assigned to undergo either sham laparotomy, splenectomy, or splenectomy with autotransplantation of the intact spleen into the pelvis and formation of vascular anastomoses to the iliac vessels. Two weeks post-operatively, the dogs received a sublethal intravenous injection of Streptococcus pneumoniae type 25. OUTCOME MEASURES: Bacterial clearances and inflammatory damage to the liver. Bacterial clearance of the autotransplanted spleen should be no different from that of a sham-operation spleen and significantly different from that of a splenectomized animal. In addition, immunologic function of the autotransplanted spleen should not differ from that of a sham-operation spleen in the degree of inflammatory damage to the liver. RESULTS: No differences in bacterial clearance function were found between the animals that had undergone sham laparotomy or splenic autotransplantation. However, bacterial clearance in the splenectomized animals was significantly impaired. Histologic examination of the liver 2 weeks after the bacterial challenge revealed high-grade inflammatory damage to the livers of splenectomized dogs, intermediate liver damage in dogs that underwent autotransplantation, and essentially no damage in dogs that underwent sham laparotomy. Autotransplanted spleens were essentially nonreactive, lacking actively proliferating germinal centers, whereas splenic tissue from sham-operation animals showed reactivity. CONCLUSION: Although bacterial clearance function is unchanged in autotransplanted spleens, this method still does not fully protect the liver from inflammatory damage.

Analysis of Variance↗

Percutaneous transluminal angioplasty in adults less than 45 years of age with premature lower extremity atherosclerosis.

Despite poor results reported with conventional vascular bypasses in young adults with ischemia from premature lower extremity atherosclerosis (PLEA), little attention has been given to alternative revascularization techniques. This study evaluated 32 patients (21 males and 11 females) < 45 years of age with PLEA who underwent 53 primary percutaneous transluminal angioplasty (PTA) procedures for treatment of 46 ischemic limbs. A residual arterial stenosis < 30% was achieved in 83% of PTA sites. Mean degree of stenosis decreased from 79.9% to 24.1% (p < 0.0001). Clinical improvement in ischemic symptoms was obtained in 39 (85%) limbs. Hemodynamic improvement was achieved in 31 (70%) of 40 limbs as documented by ankle/brachial indices. All criteria for early clinical success were met in 70%. Another 13% met all criteria except that the residual stenosis was < 50%. Hematoma and early restenosis were reported in two patients each. Mean follow-up was 27.3 months (range 1 to 84 months). Cumulative patency by life-table analysis was 81% at 1 year, 77% at 2 years, and 71% at 3 years. Thirteen (41%) patients required secondary PTA or bypass; 85% were performed within 1 year. Two patients had adjunctive bypasses; six (19%) were performed after PTA failure. Only one (3%) patient required major amputation. Neither cardiovascular risk factors, treatment indication, location of the diseased arterial segment, nor quality of distal runoff vessels predicted the need for secondary PTA or surgical procedures. PTA of the proximal arteries in young patients with PLEA is an effective primary revascularization technique with results comparable to those of conventional operative revascularization procedures.

Adult↗

Diffuse arterial thrombosis in a young man with elevated lipoprotein(a) and minimal atherosclerosis.

An increased incidence of premature atherosclerotic arterial occlusive disease was recently reported in young adults. This condition is characterized by early occurrence of severe symptoms, lower incidence of typical cardiovascular risk factors for atherosclerosis, different natural course of arterial disease vis-a-vis older population, and poor outcome of a standard treatment. This report describes a young man with aggressive arterial occlusive disease in the lower extremities and symptom-free occlusions of coronary and renal arteries in association with high levels of lipoprotein(a). Microscopic early atherosclerotic changes were noted in the occluded arteries of the amputated leg. Premature atherosclerotic arterial occlusive disease in young adults has different clinical and pathological patterns, necessitating a different approach for evaluation and treatment.

Adult↗

Lower extremity ischemia in adults younger than forty years of age: a community-wide survey of premature atherosclerotic arterial disease.

A retrospective community-wide survey identified 109 patients younger than 40 years of age with lower extremity ischemia: 72 men and 37 women, mean age 36 years (range 25 to 40 years), black-to-white ratio-1:1. Initially, 66 patients had claudication and 43 had severe ischemia. Cardiovascular risk factors were smoking (85%), hypertension (47%), coronary artery disease (30%), hyperlipidemia (27%), diabetes (25%), and visceral arteriopathy (17%). Unique risk factors included hypercoagulability (15%) and clinical arterial hypoplasia (15%). Twenty-three (21%) patients were treated medically; 74 (68%) underwent primary revascularization and 12 (11%) primary major limb amputation. Forty-six (53%) patients required secondary procedures, of which 34 (74%) were performed within 1 year of primary intervention. A total of 29 (27%) patients ultimately required amputation (10 bilateral). Women had higher prevalence of diabetes (p < 0.01), arterial hypoplasia (p < 0.05), and tendency for more severe ischemia (p = 0.11). No racial differences in severity of symptoms or outcome of treatment were found. By multiple logistic regression analysis, typical cardiovascular risk factors did not predict severity of symptoms, need for surgical treatment, or outcome. However, diabetes was associated with tissue loss (p < 0.05) and primary amputation (p < 0.001). Further, adjusted odds ratios indicate that arterial hypoplasia had a protective effect on distal vasculature (p < 0.05) and predicting need for revascularization (p < 0.05), but not on treatment failure. Hypercoagulability had the highest predictive value for presence of severe ischemia (p < 0.05), need for primary amputation (p < 0.01), and early failure of surgical treatment (p < 0.05).

Adult↗

Hypercoagulable states as an evolving risk for spontaneous venous and arterial thrombosis.

This study of 49 patients with spontaneous venous and arterial thrombosis identified 27 with hypercoagulable states: 13 had only venous thrombosis (VT), six had episodes of VT followed by arterial thrombosis (AT) and eight had AT only. All 27 patients were less than 42 years of age; 22 had specific natural anticoagulant or fibrinolytic deficiencies: antithrombin III (nine patients), protein C (eight patients), protein S (three patients), heparin cofactor II (two patients), tissue plasminogen activator release (one patient) and mixed antithrombin III and protein S (one patient). The remaining five patients had recurrent thrombotic events associated with resistance to heparin anticoagulation, but no established laboratory diagnosis. Clotting complications included recurrent VT, pulmonary embolism, multiple failed arterial procedures and lower extremity amputation. The remaining 22 patients (mean age of 53 years, range of 46 to 63 years), 12 with VT and ten with AT, did not have laboratory evidence of hypercoagulability and none had recurrent vascular occlusions. All these patients were successfully treated by conventional therapy without any additional thrombotic events during the follow-up period. Young adults with spontaneous thrombotic events should be screened for possible hypercoagulable states. Additionally, these young patients need further evaluation and treatment of cardiovascular risk factors. Those with premature atherosclerosis have an especially poor prognosis despite surgical intervention and anticoagulant therapy.

Adult↗

Rare presentation of anastomotic iliac artery false aneurysm: rupture with formation of ilio-iliac arteriovenous fistula.

A rare complication of aortoiliac bypass procedure resulting in the formation of an acute ilio-iliac arteriovenous fistula was presented. The latter was a first manifestation of anastomotic iliac pseudoaneurysm. This is only the second such case reported in the English literature. Iliac anastomotic pseudoaneurysm although rarely detected, is a potentially lethal complication that has to be repaired close to the time of its detection.

Aged↗

Bilateral neck exploration for primary hyperparathyroidism.

Controversy about the operative approach for primary hyperparathyroidism has prompted a review of our operative experience since 1980. We treated 73 patients with primary hyperparathyroidism during this 10-year period, all of whom underwent bilateral neck exploration in which the surgeons attempted to locate all parathyroid tissue. Thirty-eight patients (52%) were found to have a solitary adenoma, while 35 (48%) patients had multiple gland pathology. There were two cases of persistent hypercalcemia because of a synchronous parathyroid hormone-secreting malignancy in one patient and aberrant fifth gland adenoma in the other patient. Without bilateral neck exploration, about one-half of the patients in our series would not have been cured of primary hyperparathyroidism. Because of the high incidence of multiple parathyroid gland involvement, we conclude that thorough bilateral neck exploration must be considered the goal for surgical treatment of primary hyperparathyroidism.

Adenoma↗

The safety, efficacy, and durability of external carotid endarterectomy.

Results of 21 external carotid endarterectomies (ECEAs) in 19 patients with symptoms were reviewed retrospectively. No patients died or had new strokes referable to ECEA within 30 days of surgery. Overall, six (32%) patients died during an average 41 months of follow-up (range 1 to 134 months). Persistent symptoms followed five (71%) of seven ECEAs performed for cerebrovascular insufficiency or transient ischemic attacks. One patient treated urgently for an evolving stroke failed to improve and died after hospital discharge. Another patient with crescendo transient ischemic attacks had a preoperative deficit that did not resolve for 6 months and had a second stroke 2 years later. Another patient had a stroke after a contralateral carotid reconstruction but recovered. In contrast, only two (14%) of 14 ECEAs performed for monocular amaurosis fugax had persistent symptoms after surgery. Durability of 16 ECEAs was evaluated by arteriography or duplex scanning. Of six ECEAs closed primarily, three (50%) occluded, one has 60% restenosis, and only two (33%) had no restenosis (mean follow-up 36 months). Of 10 ECEAs closed by patch angioplasty, none occluded, 2 had 20% restenosis, and eight (80%) had no restenosis (mean follow-up 47 months). Life-table analysis indicated improvement in ECEA patency and durability with patch angioplasty (p = 0.011). From these data, ECEA can be performed with relative safety but is more effective for treatment of monocular amaurosis fugax in patients with a microembolic source at the external carotid origin. Patients with any other indications for ECEA did not benefit consistently from this operation.

Carotid Artery, External↗

Anthropometric study with emphasis on hand and foot measurements in the Prader-Willi syndrome: sex, age and chromosome effects.

Age, sex and chromosome effects on weight, height, sitting height, three head dimensions, and five hand and three foot measurements were analyzed from 57 patients (35 males and 22 females) with the Prader-Willi syndrome (PWS). No significant differences were observed in anthropometric data between PWS patients with the 15q chromosome deletion and those with normal chromosomes. Preschool children were found to have dolichocephaly, while hand and foot measurements, stature and sitting height were within normal range, although foot size was smaller than hand size in females when compared with PWS males. However, anthropometric measurements, excluding weight, head length and ankle breadth, were less than -2 SD in adult patients. Abnormal growth patterns apparently exist with significant negative correlations with age, particularly in PWS males, for height, sitting height, head circumference, and hand and foot measurements, but a significant positive correlation for weight was found in patients below 10 years of age.

Adolescent↗

Noninvasive diagnosis of vascular trauma by duplex ultrasonography.

Duplex ultrasonography was used prospectively in the initial evaluation of 198 patients with 319 potential vascular injuries of the neck and extremities. Patients who were unstable or who had obvious arterial trauma were excluded. Injury was caused by gunshot in 104 (53%), blunt trauma in 42 (21%), stab wound in 34 (17%), and shotgun in 18 (9%). Duplex ultrasonography correctly characterized and localized vascular injuries in 23 patients: arterial disruptions (13), intimal flaps (4), acute pseudoaneurysms (3), arteriovenous fistulas (2), and shotgun pellet arteriopuncture (1). Nineteen other patients had vasospasm (13) or external compression (6) without evidence of intrinsic vessel injury, these 42 studies had true-positive results. Twenty patients underwent arterial repair (13 on the basis of duplex ultrasonography alone), one had primary amputation, three required fasciotomy, and 18 were observed. Two patients with false-negative results had minor shotgun pellet arteriopunctures that were missed by duplex ultrasonography, but neither needed repair. One hundred fifty-three patients had true-negative results on duplex ultrasonography: all clinically had only proximity injuries and easily palpable distal pulses. The result of one duplex ultrasonography study was found to be false-positive on arteriography. The sensitivity of duplex ultrasonography was 95%, the specificity was 99%, and the overall accuracy was 98%. These results closely approximate those reported with the use of exclusion arteriography in the evaluation of similar vascular trauma patients. Furthermore, duplex ultrasonography has no interventional risks and is more cost-effective for screening such injuries than arteriography or exploration. Duplex ultrasonography is a reliable method of diagnosis in patients with potential peripheral vascular injuries.

Adolescent↗

Chromosome lesions which could be interpreted as "fragile sites" on the distal end of Xq.

Chromosome lesions which could be interpreted as "fragile sites" on the distal end of the long arm of the X chromosome were identified during a cytogenetic study of 160 mentally retarded adult males with no apparent cause of their mental retardation and one normal adult female with a family history of fra (X) syndrome. Peripheral blood samples were cultured in either M199 or RPMI 1640 medium with FUdR or BrdU. Metaphases were examined for chromosome lesions or fragile sites on the distal end of Xq and 3 distinct sites were observed: Xq26, Xq27.2, and Xq27.3. Other chromosome lesions at Xq28 were observed and interpreted as nonspecific telomeric structural changes. Chromosome lesions were observed in cells from 14 of the 161 individuals. These included: 5 patients with an Xq26 site, 2 with the recently reported Xq27.2 site, 4 with the Xq27.3 site (characteristic of the fra (X) syndrome), 2 with nonspecific telomeric structural changes, and one individual with 2 lesions (a nonspecific telomeric structural change and an Xq26 site). Additional research is necessary to determine the frequency and clinical significance, if any, of lesions occurring in this region of the X chromosome and to distinguish among heritable fragile sites, constitutive fragile sites, and nonspecific telomeric structural changes.

Adolescent↗

Does open fasciotomy contribute to morbidity and mortality after acute lower extremity ischemia and revascularization?

A retrospective review was undertaken of 127 lower extremity fasciotomies performed for compartment syndrome after acute ischemia and revascularization in 73 patients with vascular trauma and 49 patients with arterial occlusive disease. One hundred twelve (88%) fasciotomies were performed early (at the time revascularization); 15 (12%) were delayed because of late compartment syndrome diagnosis. Ninety-four (77%) patients had more than one accepted indication for fasciotomy. Double-incision fasciotomy was used in 98 (77%) extremities, single-incision fasciotomy was used in 19 (15%), and fasciotomy-fibulectomy was used in 10 (8%). Fasciotomies were closed in 88 (69%) patients an average of 14 days after surgery. Seven patients needed multiple skin grafting procedures or myocutaneous flaps to close the wound; none compromised limb salvage. Five other patients had minor wound infections that resolved. Functional status returned to preoperative levels by the time of discharge from the hospital in 59 (48%) patients. Thirty-one (24%) patients had residual lower extremity disability related to delayed union of the fracture (five), chronic neuropathy (20), leg swelling (one), or ischemic nonhealing fasciotomy wounds (three); two patients had unrelated disabilities. Fourteen (11%) amputations were required for refractory limb ischemia; two (1.6%) were required for wet gangrene of the foot, which infected the fasciotomy site; the others had open noninfected incisions. Eighteen (15%) patients died of cardiopulmonary failure or multisystem failure or both, without fasciotomy-related problems. Open fasciotomy for compartment syndrome after acute lower extremity ischemia and revascularization was associated with an increased risk of minor wound morbidity. However, limb loss and death resulted from persistent ischemia and underlying systemic disease processes or injuries, but not from open fasciotomy wound complications.

Adolescent↗

Principles of flow cytometry.

Flow cytometers can analyze a populations of cells, one at a time, at rates of 1,000 to 10,000 cells per second. They can provide distributions of parameters, not just the MCV. A broad variety of measurement parameters is available, ranging from simple sizing to esoteric measures of membrane fluidity or epitope density. The resulting analysis gives low resolution compared to imaging of cells but gives excellent statistical samples of the parameters that it can detect. The parameter values for individual cells can be correlated, and displayed in a variety of multi-dimensional formats. When the analysis reveals subsets of cells, it is possible to sort the detected subsets of cells into separate chambers for further culture or test. Flow cytometers are already in clinical laboratories, performing size analysis in multiparameter hematology instruments. As you have seen, this usage barely scratches the surface of the capabilities of this technology. It now remains for the research clinician to adapt flow cytometry to a broader range of useful clinical applications.

Calibration↗

Traumatic hemipelvectomy.

Management of patients who have suffered traumatic hemipelvectomy is one of the most difficult challenges to confront a trauma surgeon. We present a case of a female survivor of traumatic hemipelvectomy and factors in the care of these patients that can lead to a successful outcome.

Accidents, Traffic↗