Metals tolerance in moderately thermophilic isolates from a spent copper sulfide heap, closely related to Acidithiobacillus caldus, Acidimicrobium ferrooxidans and Sulfobacillus thermosulfidooxidans.

Selective enrichments enabled the recovery of moderately thermophilic isolates with copper bioleaching ability from a spent copper sulfide heap. Phylogenetic and physiological characterization revealed that the isolates were closely related to Sulfobacillus thermosulfidooxidans, Acidithiobacillus caldus and Acidimicrobium ferrooxidans. While isolates exhibited similar physiological characteristics to their corresponding type strains, in general they displayed similar or greater tolerance of high copper, zinc, nickel and cobalt concentrations. Considerable variation was found between species and between several strains related to S. thermosulfidooxidans. It is concluded that adaptation to metals present in the bioleaching heap from which they were isolated contributed to but did not entirely explain high metals tolerances. Higher metals tolerance did not confer stronger bioleaching performance, suggesting that a physical, mineralogical or chemical process is rate limiting for a specific ore or concentrate.

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines.

Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells in vivo (doubling time 53-442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures. In vitro glucocorticoid resistance correlated well with that measured ex vivo, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and L-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC50 > 8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating in vivo selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.

Posterior glenohumeral subluxation: active and passive stabilization in a biomechanical model.

UNLABELLED: We examined the role of the glenohumeral and coracohumeral ligaments as well as the forces provided by the rotator cuff muscles, the long head of the biceps, the anterior and middle deltoids, and the pectoralis major in the stabilization of the glenohumeral joint in the posterior direction. Simulated muscle forces were mechanically applied to eight shoulder specimens. The humeroscapular position for testing simulated the 90-degree forward-flexion (humerothoracic) position used clinically for the so-called jerk test, which is the most clinically important position with regard to posterior instability of the shoulder. Experiments were performed with a variety of configurations of ligamentous and capsular cuts, humeral rotation, and levels of muscle force. Stability was investigated by measuring the force required to subluxate the humeral head a specified amount from its reduced position. Of the muscles and ligaments tested, the subscapularis muscle contributed the most to this subluxation force. The coracohumeral ligament was an effective contributor in neutral humeral rotation, and the inferior glenohumeral ligament was an effective contributor in internal humeral rotation. The long head of the biceps was found to reduce the subluxation force in certain positions. CLINICAL RELEVANCE: It is widely agreed that a complex interaction of passive and active stabilizing structures and forces is necessary for clinical stability of the shoulder. The present study identified the contributions of ligaments and muscles to posterior stability of the shoulder in the position of greatest clinical importance--posterior subluxation with the shoulder in forward flexion.

Laparoscopic tension-free repair of large paraesophageal hernias.

The paraesophageal hernia is an unusual disorder of the esophageal hiatus that may be associated with life-threatening mechanical problems. Elective repair is recommended at the time the condition is diagnosed, and open surgery can be accomplished with a low incidence of complications. The option of performing these repairs through a laparoscopic approach may further reduce morbidity and recovery time associated with surgical intervention. The purpose of this report was to review available options for laparoscopic repair and to present our experience with a tension-free technique for large paraesophageal hernias. Three patients with large diaphragmatic defects had laparoscopic repairs using an expanded polytetrafluorethylene (PTFE) patch secured with intracorporeal suturing techniques. One of these patients also underwent laparoscopic Toupet fundoplication in conjunction with repair of the hernia. In the other two patients, the fundus was secured to the right diaphragmatic crus to reduce the potential for recurrence and minimize postoperative reflux symptoms. All patients underwent successful repair without perioperative complications and had excellent long-term results. Laparoscopic repair of paraesophageal hernias can be accomplished by a number of different reported techniques. The use of a tension-free repair with PTFE may be particularly suitable for large diaphragmatic defects. An antireflux operation may be added selectively depending on clinical circumstances.

Optical modeling of radial keratotomy incision patterns.

PURPOSE: To determine the optical effects of higher-order corneal shape variations resulting from radial keratotomy. METHODS: Videokeratoscopic height data were obtained postoperatively from several patients who had undergone radial keratotomy. For each of clear central zone sizes 3.00 mm, 4.00 mm, and 4.75 mm, two patients were chosen randomly from the larger study group. Data obtained 2 weeks postoperatively from these six patients were decomposed into the Zernike polynomials, and the low-order expansion terms were removed to disclose corneal height variations (the radial keratotomy artifact). The artifact was applied to a schematic eye model, and exact ray-tracing was used to evaluate visual performance, which was defined as a function of pupil diameter, optical zone (central clear zone) size, and radial keratotomy artifact centration. RESULTS: The radial keratotomy artifact degrades visual performance at midspatial frequencies more than it does at high spatial frequencies. This effect is most pronounced for smaller optical zones and for a pupil diameter of 4 mm. Visual performance remains nearly constant for small decentration (0.5 mm or less) of the radial keratotomy optical zone from the corneal apex. CONCLUSIONS: Residual refractive error, corneal asphericity, and the radial keratotomy artifact all affect visual performance after radial keratotomy. Isolated effects of the radial keratotomy artifact degrade visual performance, with the level of degradation dependent on pupil size, optical zone size, and centration of the procedure. More research is necessary to combine the radial keratotomy artifact with changes in corneal asphericity and to further quantify the optical effects of radial keratotomy.

Endothelial barrier function and Na+/K(+)-ATPase pump density in herpetic stromal disease.

PURPOSE: Corneal edema is a significant component of the various forms of herpes simplex virus type 1 (HSV-1)-induced stromal disease. Maintenance of corneal thickness, a reflection of corneal hydration, depends on a physical barrier formed by endothelial cell-cell junctions and by the activity of Na+/K(+)-ATPase pumps that regulate ion flux and thus influence water movement through this cell layer. These functions were measured in corneas with increased corneal thickness caused by HSV-1-induced stromal disease to determine their contribution to the pathogenesis of the edema. METHODS: Stromal disease with corneal edema was induced in rabbits by intrastromal injection of the RE strain of HSV-1. At various times after infection, during the development of and recovery from stromal disease, endothelial barrier function and Na+/K(+)-ATPase pump sites were measured in excised rabbit corneas. RESULTS: The endothelial permeability coefficient, Ktrans, for 14C-dextran, 3H-inulin, and 14C-mannitol, were not altered significantly during periods of maximal corneal edema and stromal disease. Endothelial Na+/K(+)-ATPase pump density, as measured by ouabain binding, showed a statistically significant (P < 0.05) decrease in HSV-1-infected corneas during peak edema compared to mock antigen-injected or uninjected control corneas. Pump density returned to baseline values by 24 days after infection, concurrent with the resolution of corneal edema. CONCLUSIONS: These results indicate that corneal endothelial barrier function was not altered in this form of HSV-1-induced stromal edema; however, pump density was reduced significantly.

Test-retest reliability of eccentric peak torque values for shoulder medial and lateral rotation using the Biodex isokinetic dynamometer.

In order for the Biodex isokinetic dynamometer to be used in clinical research, it must be documented to be a reliable measurement tool. The purpose of this study was to determine eccentric peak torque test-retest reliability for glenohumeral medial and lateral rotator muscles using the Biodex isokinetic dynamometer. Eighteen healthy men and women volunteers ranging in ages from 18 to 30 who exhibited no prior history of glenohumeral injury were studied. The subjects were tested bilaterally for eccentric glenohumeral medial rotation (MR) and lateral rotation (LR) at 90 and 120 degrees/sec using 0 degrees of shoulder abduction so that the subject's arm was in contact with his or her trunk. Seven days following the initial test, a retest was administered using the identical protocol. Data collection of pretesting and posttesting was done using the IBM basic computer and the Biodex software program. Test data were analyzed using the intraclass correlation coefficient. The test-retest results indicated: dominant LR at 90 degrees/sec, r = 0.86, and at 120 degrees/sec, r = 0.83; dominant MR at 90 degrees/sec, r = 0.76, and at 120 degrees/sec, r = 0.77; nondominant LR at 90 degrees/sec, r = 0.76, and at 120 degrees/sec, r = 0.83; and nondominant MR at 90 degrees/sec, r = 0.75, and at 120 degrees/sec, r = 0.83. The results demonstrate the isokinetic eccentric mode of the Biodex dynamometer to be reliable for the test-retest measure of peak torque. These data may be used to support future clinical research of the eccentric isokinetic mode of the Biodex isokinetic dynamometer.

Adenocarcinoma of the small intestine: 21-year review of diagnosis, treatment, and prognosis.

BACKGROUND: The purpose of this study was to evaluate the tumor characteristics and treatment associated with an improved overall survival in patients with adenocarcinoma of the small intestine. METHODS: The records of all patients with primary adenocarcinoma of the small bowel seen between January 1971 and December 1991 were reviewed retrospectively. The study comprised 38 patients, 22 (58%) with duodenal tumors, 11 (29%) with jejunal tumors, and five (13%) with ileal tumors. RESULTS: Although not statistically significant, the patients with duodenal adenocarcinoma lived longer than the patients with jejunal or ileal lesions (p = 0.77). The overall survival was 23% and seemed to correlate best with absence of lymph node metastases (p = 0.04) and pancreaticoduodenectomy for localized duodenal tumors (p = 0.04). The patient's age, duration of symptoms, disease-free interval, tumor location, type of recurrence, and histologic grade did not significantly influence survival. CONCLUSIONS: The lethality of small-intestinal adenocarcinoma appears to be related to a delay in diagnosis and treatment. When a definitive surgical procedure is performed before lymph node metastases appear, the patient's chance for long-term survival is greatly improved.

Results of aggressive treatment of gastric sarcoma.

BACKGROUND: Leiomyosarcoma and leiomyoblastoma and subtypes of gastric smooth muscle tumors. These rare tumors are usually treated with surgical resection. However, there is controversy regarding the optimal surgical management for these malignancies and little information is available on the efficacy of radiation and chemotherapy in the adjuvant or palliative setting. METHODS: The records of 32 patients with gastric leiomyosarcoma or leiomyoblastoma were reviewed. Survival data were obtained and patient outcome was analyzed with respect to the type of treatment given. Four different staging systems were compared for their ability to predict survival. RESULTS: Thirty patients with leiomyosarcoma and two patients with leiomyoblastoma were followed after surgery. All 32 patients were explored, and 21 curative and 11 palliative procedures were performed. Adjacent organs were included in 38% of resections. Only three patients did not undergo gastric resection. Local recurrence developed in eight patients after curative resection for a local control rate of 62%. Eight other patients developed metastatic disease for an overall recurrence rate of 76% after curative resection. Median survival of patients undergoing curative resection was 40 months compared with 8 months for those having a palliative procedure. The estimated 5-year survival was 34% and 10%, respectively (p = 0.05). Twenty-five patients with advanced disease received systemic, hepatic arterial, or intraperitoneal chemotherapy. Eighty percent of patients received a regimen including doxorubicin. Four partial and one complete response were noted. Seven patients received postoperative radiation therapy. Fourteen patients underwent debulking surgery of recurrent or persistent disease in conjunction with chemotherapy. Chemotherapy, radiation therapy, and debulking surgery did not result in statistically significant prolongation of survival. Seven patients remain alive, two with liver metastases. Four different staging systems for gastric sarcomas were compared, but none of them were found to be clearly superior in predicting survival. CONCLUSIONS: Curative gastric resection was achieved in 66% of patients and resulted in a significant prolongation of survival as compared with patients who had a palliative procedure. Wedge resection of tumor or partial gastric resection appears to be an acceptable surgical approach to these tumors as long as negative margins can be obtained. Chemotherapy, radiation therapy and debulking surgery did not result in significant prolongation of survival in the face of advanced disease. None of the staging systems for gastric sarcoma currently in use is completely satisfactory. Tumor grade and extent of disease seem to be the most important factors when determining prognosis or considering adjuvant therapy.

Breast biopsy in women 30 years old or less.

Forty women 30 years of age or less underwent breast biopsy at Roswell Park Cancer Institute between January 1980 and January 1989. Thirty-eight of the 40 women had a palpable breast mass. Thirty-one of these young women had self-detected breast masses, and the median duration before presentation was 6 months. Physical characteristics were described in 30 of the masses. Twenty-three were described as "fibroadenomas" or smooth, firm, and mobile. Seven masses were described as irregular. The median size of the breast mass was 1.5 cm (range: 0.5 to 9.0 cm). Mammography was performed in 20 patients, but results were reported as abnormal in only 6. Twenty of the masses were described histologically as fibroadenoma. Twelve were described histologically as "fibrocystic disease" or "stromal fibrosis." One case (2.5%) was invasive adenocarcinoma. Probability of serious underlying breast pathology in young women is low but not nil. Noninvasive and minimally invasive techniques are proposed by some authors as cost-efficient methods that may substitute for open biopsy in these patients. Unfortunately, false-negative results persist and are particularly unacceptable in these young women. During the same time period as our study, 54 women aged 30 years or less were referred to Roswell Park Cancer Institute with a previously diagnosed invasive breast cancer. The incidence of breast cancer in this biopsy series was 2.5%. The potential costs of misdiagnosed early breast cancer in young women negate any rationalization for less invasive biopsy techniques. Following aspiration to rule out a benign cyst, and a possible period of brief observation for spontaneous resolution (2 or 3 months), excisional biopsy is recommended for young women with a breast mass.

Contact lens-related infectious keratitis.

Infectious keratitis is the most serious complication of contact lens use. Virtually all contact lens wearers are at risk. Initial therapy consists of frequent broad-spectrum fortified antibiotic drops after appropriate laboratory workup. Pseudomonas and Acanthamoeba species are the most important causes of contact lens-associated ulcers. Acanthamoeba keratitis produces significant ocular morbidity, and treatment is not always effective. Recent studies have provided new insights regarding the incidence, risk factors, and pathogenesis of contact lens-related infectious keratitis. Extended-wear soft contact lens wearers are at greatest risk. With our present understanding of the pathogenesis and risk factors of contact lens-related infectious keratitis, daily-wear schedules are strongly advised. Even under the best of lens care conditions, infectious keratitis may still occur. It is therefore imperative that patients be informed to remove their lenses and seek medical evaluation if any discomfort develops.

Sodium activity in the aqueous humor and corneal stroma of the rabbit.

The present study examined the free sodium concentration of the aqueous humor and corneal stroma of both transparent and non-transparent corneas to assess the transendothelial activity gradient for sodium. In the transparent cornea of the adult rabbit, the sodium activity was higher in the aqueous humor than the stroma. This difference in sodium activity would cause water to diffuse down its concentration gradient from stroma to aqueous humor. In this way corneal transparency and the deturgesced state are maintained. Removal of the corneal endothelium in the adult rabbit produced an opaque swollen cornea. Under these conditions the sodium activity was higher in the stroma than the aqueous humor. However, an osmotic gradient was not produced by the Na+ activity gradient because the endothelium was not present to act as a semi-permeable membrane. The corneal endothelium was no longer present to establish and sustain the activity gradient for sodium that is necessary for corneal transparency in the mature rabbit. The transendothelial sodium activity gradient was also measured in 13-day-old rabbits. At this age, the cornea was not yet transparent, nevertheless the free sodium concentration of the aqueous humor was higher than that of the stroma, similar to the adult transparent cornea. This suggests that forces other than the establishment of the proper transendothelial sodium gradient are responsible for the lack of corneal transparency in the young rabbit.

Prevalence of gene sequences coding for hypervariable regions of Opa (protein II) in Neisseria gonorrhoeae.

Opas (protein IIs) are a family of surface-exposed proteins of Neisseria gonorrhoeae. Each strain of N. gonorrhoeae has multiple (10-11) genes encoding for Opas. Identifiable elements in opa genes include the coding repeat within the signal sequence, conserve 5' and 3' regions, and hypervariable regions (HV1 and HV2) located within the structural gene. N. gonorrhoeae strains appear to have many biological properties in common that are either HV-region-mediated or associated with the presence of specific HV regions, suggesting that HV regions could be found in many clinical isolates. Oligonucleotides from three source strains representing three conserved regions of opa, 12 HV1 regions, and 14 HV2 regions were used by dot blot analysis to probe 120 clinical isolates of N. gonorrhoeae. The probe for the coding repeat hybridized to all 120 strains, the 3' conserved-region probe reacted with 98% of the strains, and the 5' conserved-region probe with 90% of the strains. Nine HV1 probes hybridized to 3.3-39.2% of the strains, and 13 of the HV2 probes hybridized to 1.7-25% of the isolates. Analysis of the number of probes that hybridized to each of the isolates showed that 19% did not hybridize with any of the HV1 probes and 25% did not hybridize with any of the HV2 probes. Approximately three-quarters of the isolates hybridized with one, two or three of the HV1 probes or one, two or three of the HV2 probes; 89% of the isolates hybridized to least one HV1 or one HV2 probe. The data indicate that some genes encoding HV regions of N. gonorrhoeae Opa proteins are widely distributed in nature.

Colorectal adenocarcinoma in patients less than 40 years of age.

From 1973 to 1985, 105 patients under 40 years of age were treated for colorectal adenocarcinoma at Roswell Park Cancer Institute. There were 51 males and 54 females. The mean age was 32 years. The majority of patients were treated for left colon or rectal carcinomas. Ninety-seven of 105 patients underwent surgical resection of their primary cancer, 70 (67 percent) of which were potentially curative. Twenty-seven patients underwent palliative resections. Dukes' A or B lesions were not seen in patients less than 20 years old, whereas these early lesions were seen in 11 percent of patients 20 to 29 years old and in 26 percent of patients greater than 30 years of age. The mean survival for patients between 20 and 29 years was 39 months and 46 months for patients 30 years and older.

Treatment options and recurrence potential for cystosarcoma phyllodes.

The surgical treatment and outcome of 31 women with a pathologic diagnosis of cystosarcoma phyllodes at Roswell Park Memorial Institute were reviewed. Surgical excision was performed upon 20 patients with a mean tumor size of 4.5 centimeters (range of 1.0 to 9.0 centimeters). Mastectomy was performed initially upon 11 patients with a mean tumor size of 15 centimeters (range of 3 to 40 centimeters). Local recurrence was seen in five patients treated by excision and one patient treated by mastectomy. All patients retreated by repeat excisions were controlled; one patient retreated with mastectomy died with local recurrence and distant disease. Routine axillary dissections were not performed. Involvement of the axillary lymph nodes occurred in one patient and was associated with advanced systemic disease. Local recurrences did not imply associated systemic spread and were controlled in five of six patients by repeat excision or mastectomy. Although the benign behavior of this tumor is commonly emphasized, four of the patients we studied died of malignant spread of cystosarcoma phyllodes.

Combined hamartomas of the retinal pigment epithelium and retina.

Combined hamartomas of the retinal pigment epithelium (RPE) and retina are rare, benign lesions usually occurring in individuals with no underlying systemic abnormalities. The authors report two cases of combined hamartomas of the RPE and retina. In one case, combined macular hamartomas of the RPE and retina were present in a 5-month-old infant. This is the earliest reported case of bilateral macular involvement. In both patients, multiple cafe-au-lait spots were present, and the diagnosis of neurofibromatosis was considered. The authors suggest that combined hamartomas of the RPE and retina are congenital lesions and may be one of the ophthalmic manifestations of the phakomatoses.

Analysis of shoulder rotation accompanying a proprioceptive neuromuscular facilitation approach.

The purpose of this study was to determine whether the medial rotation that accompanies flexion of the shoulder took place during the performance of the flexion-abduction-lateral-rotation proprioceptive neuromuscular facilitation pattern (D2F) with the forearm moving in supination and the elbow remaining in extension. The dominant shoulders of 10 volunteer subjects (8 men and 2 women) between 18 and 30 years of age and with no known pathological conditions of the dominant upper extremity were examined. The amount of shoulder flexion was determined by using a gravity-activated angle finder placed on the superior surface of the humerus at the beginning and ending phases of motion. The amount of shoulder rotation was determined by using a universal goniometer, a square ruler, and a gravity-activated angle finder with its base resting on the surface of an adjustable wooden bracket aligned over the humeral epicondyles. The results for all subjects showed that, as the D2F pattern was performed, lateral rotation occurred during the initial phase of motion that was followed by a palpable change to medial rotation. The analysis of variance and Scheffé tests demonstrated significant differences (p less than .01) between the amount of medial rotation at the beginning of the pattern and the point at which the rotational direction changed and between this point and the end of the pattern. Physical therapists should be aware that the flexion-abduction-lateral-rotation pattern should end with the shoulder in medial rotation when they guide and apply resistance to patients performing this PNF pattern.

Documentation of medial rotation accompanying shoulder flexion. A case report.

We dissected a fresh cadaver to determine which glenohumeral structures causes medial rotation of the humerus during flexion in the sagittal plane. All structures associated with both shoulders were dissected thoroughly. Both elbows were disarticulated to expose the distal end of each humerus to be used as measurement landmarks. We used a universal goniometer for measurements of shoulder flexion. To determine which structures cause passive medial rotation, the associated shoulder muscles, ligaments, and the capsule were individually reflected from the humerus. Passive shoulder flexion to the point where medial rotation started was measured after each structure was resected. The end passive glenohumeral flexion without rotation was 60 degrees after reflection of all musculature and other periarticular shoulder structures. Our results support Steindler's conclusion that during flexion of the humerus beyond the horizontal there is forced rotation caused by ligamentous tension. We also found that the bony configuration of the glenohumeral joints also plays an important role in medial rotation accompanying shoulder flexion.