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Biomedical subjects

S M Roe

Publications and source records attributed to S M Roe.

28 records · Page 2Linked to original sources

Potassium and ventilation during exercise above and below the ventilatory threshold.

Increases in arterial plasma potassium during exercise may provide an important drive to ventilation. We examined the changes in arterialized venous plasma potassium concentration ([K +]av) and ventilation that occur during sustained exercise at workloads above and below the ventilatory threshold (Vt) in young health humans. After the onset of exercise at a workload below-Vt, [K +]av rose by 0.3 (+/- 0.1) mmol l-1 (mean +/- SEM). Following 30 min of exercise at this intensity [K +]av had fallen (P < 0.05, ANOVA) by an amount approximately equal to one third of the initial increase. While [K +]av fell, ventilation remained stable. At 5 min after the onset of sustained exercise above the Vt [K +]av had risen by 0.7 (+/- 0.1) mmol l-1 and thereafter remained constant. Ventilation slowly increased throughout the above-Vt protocol. These results show significant differences in the time course of the changes in [K +]av and ventilation. They do not support the hypothesis that changes in [K +]a during moderate exercise cause linearly related changes in ventilation.

Adult↗

A molecular clamp in the crystal structure of the N-terminal domain of the yeast Hsp90 chaperone.

Hsp90 is a highly specific chaperone for many signal transduction proteins, including steroid hormone receptors and a broad range of protein kinases. The crystal structure of the N-terminal domain of the yeast Hsp90 reveals a dimeric structure based on a highly twisted sixteen stranded beta-sheet, whose topology suggests a possible 30-domain-swapped structure for the intact Hsp90 dimer. The opposing faces of the beta-sheets in the dimer define a potential peptide-binding cleft, suggesting that the N-domain may serve as a molecular 'clamp' in the binding of ligand proteins to Hsp90.

Amino Acid Sequence↗

Postoperative pulmonary complications and morbidity after abdominal aneurysmectomy: a comparison of postoperative epidural versus parenteral opioid analgesia.

Patients undergoing aortic aneurysm repair have a high prevalence of coexisting cardiac and pulmonary disease, and the postoperative recovery is especially delayed by pulmonary complications. A review of all elective abdominal aneurysm repairs over a 29-month period was undertaken to evaluate the effectiveness of postoperative epidural analgesia in decreasing morbidity and mortality, and specifically pulmonary complications. Patients were placed into two groups; Group 1 (34 patients) used an epidural catheter for postoperative pain control, and Group II (31 patients) used standard parenteral opioid analgesia. The two groups were similar in preoperative combined factors including known risk factors for atherosclerotic cardiovascular disease, preexisting cardiac or pulmonary disease, and preexisting renal insufficiency. A statistically significant decrease (P = < 0.05) was found in both cardiac (P = 0.0002) and pulmonary (P = 0.019) complications in comparison, favoring Group I patients. A significant decrease was also seen in the time to liquid intake (P = 0.044), time out of bed to a chair (P = 0.002), length of stay in the Intensive Care Unit (P = 0.024), and overall hospital charges (P = 0.046) in favor of Group I patients. Although no significant difference (P = > 0.05) was seen in decreasing time to ambulation (P = 0.054), average time required on the ventilator (P = 0.053), or hospital days (P = 0.181), all of these did show a trend in favor of epidural catheter utilization. There were no complications or infections related to the use of the epidural catheter during this study period. In conclusion, the use of an epidural catheter for postoperative pain control has been shown to decrease time of intubation, time in the ICU, number of cardiac and pulmonary complications, which should lead to an overall decrease in hospital charges after elective repair of abdominal aortic aneurysms.

Aged↗

Bringing core biopsy into a surgical practice.

Minimally invasive diagnostic techniques in evaluating patients with breast disease have been increasingly utilized and accepted by physicians and patients over recent years. The incorporation of stereotactic core needle biopsy and ultrasound-guided core needle biopsy into the office practice of evaluating patients with breast disease by our surgical faculty has been met favorably. These procedures are readily learned by surgeons. The judicious use of these procedures is evidenced by the malignancy rate of core biopsies of 16 per cent, identical to the historical rate for needle localization assisted excisional biopsy at our institution. Core breast biopsy expedites definitive diagnosis and optimizes patient convenience. Reimbursement is highly variable, and active physician participation in negotiating with payors to insure that costs are met is essential.

Biopsy, Needle↗

Metastatic papillary thyroid carcinoma presenting as a primary renal neoplasm.

Clinically detectable thyroid cancer metastatic to the kidney is rare, with only six cases reported in the medical literature. Four of these have been follicular carcinoma, one papillary carcinoma, and one described as a thyroid adenoma. All of these had known thyroid neoplasms prior to development of their renal metastases. We report herein a seventh case of thyroid carcinoma metastatic to the kidney, unique in that the diagnosis of the kidney metastasis preceded the knowledge of the primary thyroid neoplasm. Furthermore, the follicular variant of papillary cancer, present in this case, has not been previously described in renal metastases from thyroid cancer. Treatment of the kidney metastases led to the subsequent discovery and treatment of the primary thyroid cancer. The patient underwent nephrectomy followed by total thyroidectomy, and is alive and disease-free 3 years postoperatively. Thyroid cancer metastatic to the kidney is rare clinically, but can be amenable to treatment with good long term results.

Aged↗

Cost-effectiveness of preoperative localization studies in primary hyperparathyroid disease.

OBJECTIVE: To evaluate the effect of preoperative localization studies on the surgical management of patients with primary hyperparathyroid disease (PHPT). SUMMARY BACKGROUND DATA: Reported cure rates of initial surgical exploration for PHPT are close to 95%. Preoperative localization studies are frequently obtained to improve surgical success and decrease operative time. METHODS: Initial cervical exploration was performed in 113 patients with PHPT from 1981 to 1993. Twenty-four patients (21%) had surgery without preoperative localization studies. The remaining 89 patients (79%) had 132 noninvasive preoperative localization studies. Success of the localization studies in tumor localization, pathologic findings, postoperative serum calcium levels, and operative times were compared. Patient costs of the studies were calculated. RESULTS: Disease was identified during operation in 23 of 24 patients (96%) having cervical exploration without preoperative localization studies, and they had normal calcium levels after surgery. Eighty-seven of 89 patients (98%) having preoperative localization studies were surgically cured. The highest sensitivity rate (60%) and highest positive predictive value (79%) of the localization studies were found with thallium-technetium scintiscanning. Average cost of the localization studies was $901 per patient. Combination studies were obtained in 32 patients at an average cost of $1,314 per patient without improving sensitivity. Mean operating time did not differ for localized and nonlocalized patients. CONCLUSIONS: Preoperative localization studies did not improve parathyroid localization or cure rate and did not substantially shorten operating time in initial cervical exploration for PHPT. The economic burden of routine preoperative localization studies in these patients is not justified.

Adult↗

Calciphylaxis: early recognition and management.

Calciphylaxis, a syndrome of disseminated calcification found in chronic renal failure patients with secondary hyperparathyroidism, results in soft tissue calcification and vascular medial calcinosis leading to subsequent ischemic tissue necrosis. It is a rarely occurring condition in which patients present with painful, violaceous, mottled lesions of the extremities and/or trunk that progress to skin and subcutaneous tissue necrosis, non-healing ulcers, and gangrene. We reviewed the clinical course of seven patients (aged 24-69) with calciphylaxis treated at our institution over a 4-year period (October 1988-June 1992). All seven patients underwent parathyroidectomy, with a mean time of 8 weeks (range 3-20 weeks) between the onset of calciphylactic symptoms and parathyroidectomy. Four patients died, three secondary to wound-related sepsis. Of the three survivors, two healed soft tissue lesions primarily. The other required extremity amputation and wound excision before healing. Neither anatomical location of the soft tissue lesions nor post-parathyroidectomy serum calcium and phosphorus levels had any bearing on wound healing or mortality. Lesion severity at the time of parathyroidectomy appeared to best correlate with clinical course. Although treatment with phosphate-binding antacids, total or subtotal parathyroidectomy, and avoidance of challengers such as Vitamin D or local tissue trauma remain the mainstays of therapy, the uniform cure for calciphylaxis remains elusive. Prognosis for patients with calciphylaxis is dismal, even following late surgical intervention. Earlier recognition of the signs and symptoms of calciphylaxis should lead to timely parathyroidectomy in the hopes of ameliorating the symptoms and preventing or retarding its progressive sequelae.

Adult↗

Atomic resolution (0.83 A) crystal structure of the hydrophobic protein crambin at 130 K.

To enhance the already high quality of diffraction data for crystals of the hydrophobic protein crambin, X-ray data were collected at 130 K by the method of H. Hope to 0.83 A resolution. Refinement with PROLSQ yields a model with an R value of 10.5%. The final model had three parameter anisotropic vibration factors for all atoms, which included 367 protein heavy atoms, 372 hydrogen atoms and 144 solvent atoms with one ethanol molecule. Dihedral angles and hydrogen-bonding distances generally agree with earlier studies of high-resolution protein structures, but some new patterns are noted. Solvent-related helix distortions are reminiscent of those described by others. Helix and beta-sheet regions show distinct patterns in their side-chain conformations. Despite crambin's hydrophobic nature, its accessible surface area in the crystal is surprisingly close to that of water-soluble proteins like myoglobin and carboxypeptidase A. More of crambin's hydrophobic surface is buried in the crystal, perhaps accounting for its high order of diffraction. A total of 24% of the 46 residues show discrete disorder at 130 K. This includes five side-chains at both 300 and 130 K, and six more side-chains and an ethanol molecule at 130 K. Disorder is associated with the sequence microheterogeneity at Pro/Ser22 and Leu/Ile25, with space filling or with solvent disorder. Correlated conformations extend over three to five residues. The patterns of disorder in this structure reveal important principles of protein structure and its dynamics. Finding disordered groups correlated over 5 to 8 A suggests that co-ordinated motion extends in groups rather than simply as uncorrelated movement around an atom center. Thermal diffuse scattering experiments on insulin and lysozyme are consistent with this interpretation. Nearly all of the protein-bound solvent has been located. Less than 1% of protein accessible surface area remains uncovered by solvent or crystal contacts. Preliminary analysis of the solvent network reveals two main networks in each of four solvent regions.

Crystallography↗

Patterns for prediction of hydration around polar residues in proteins.

The atomic co-ordinates of seven very high resolution (< 1.4 A) proteins have been used to define a water-hydrogen bond template for five polar side-chains (arginine, aspartic acid, glutamic acid, asparagine and glutamine). The average water molecule positions determined were consistent with the hydrogen bonding stereochemistry expected for each side-chain. Hydrogen bonding geometry around nitrogen atoms was significantly better localized than around oxygen atoms, perhaps because of the proton on nitrogen. A prediction algorithm written to locate water molecule sites around these side-chains from the protein co-ordinates only was tested for crambin as well as for two high resolution protein structures not included in the hydrogen bond data base. The root-mean-square deviation of the predicted positions from the crystallographically determined ones for these structures was better than the resolution of these structures. The method also successfully predicted water positions for X-ray refinement of two proteins, indicating that predicted water molecules are within the radius of convergence of refinement. This method has utility for X-ray models as well as for analysis of enzyme hydration and function.

Algorithms↗