Knee and hip joint biomechanics are gender-specific in runners with high running mileage.

Female runners are reported to be more prone to develop specific knee joint injuries than males. It has been suggested that increased frontal plane joint loading might be related to the incidence of these knee injuries in running. The purpose of this study was to evaluate if frontal plane knee and hip joint kinematics and kinetics are gender-specific in runners with high mileage. 3D-kinematics and kinetics were recorded from 16 female and 16 male runners at a speed of 3 m/s, 4 m/s, and 5 m/s. Frontal plane joint angles and joint moments were ascertained and compared between genders among speed conditions. Across all speed conditions, females showed increased hip adduction and reduced knee adduction angles compared to males (p < 0.003). The initial peak in the hip adduction moment was enhanced in females (p = 0.003). Additionally, the hip adduction impulse showed a trend towards an increase in females at slow running speed (p = 0.07). Hip and knee frontal plane joint kinematics are gender-specific. In addition, there are indications that frontal plane joint loading is increased in female runners. Future research should focus on the relationship of these observations regarding overuse running injuries.

Effects of alpha-difluoromethylornithine and recombinant interferon-alpha 2 on the growth of a human renal cell adenocarcinoma xenograft in nude mice.

The effects of human recombinant interferon-alpha 2 (IFN-alpha 2) and alpha-difluoromethylornithine (DFMO) as single agents and in combination were studied for efficacy against the renal cell adenocarcinoma (JDF-1) in an in vitro clonogenic assay and in vivo as xenografts in nude mice. In vitro studies showed dose-dependent inhibition of JDF-1 colony formation by IFN-alpha 2. DFMO alone did not significantly inhibit colony formation even though ornithine decarboxylase activity was significantly inhibited. The combination of IFN-alpha 2 and DFMO synergistically inhibited JDF-1 colony formation. The synergism was more readily observed at low IFN-alpha 2 concentrations. In vivo studies showed a similar tumor growth inhibition pattern. JDF-1 tumors were implanted s.c. in nude mice, and drugs were administered continuously by Alza minipumps (IFN-alpha 2) and in drinking water (DFMO) for 28 days. IFN-alpha 2 alone significantly inhibited JDF-1 growth, while DFMO alone had no significant inhibitory effect. The combination of IFN-alpha 2 and DFMO inhibited tumor growth in an apparent additive manner at the doses used. This was reflected in the mean tumor weights obtained at the termination of the experiment: control, 1484 +/- 187 (S.E.) mg; DFMO only, 1106 +/- 129 mg; IFN-alpha 2 only, 941 +/- 186 mg; and DFMO plus IFN-alpha 2, 620 +/- 109 mg. Assessment of mouse natural killer cell activity at the time of sacrifice showed that DFMO inhibited natural killer cell activity, while IFN-alpha 2 had no effect. DFMO was observed to inhibit ornithine decarboxylase activity in JDF-1 tumors by 78%, IFN-alpha 2 by 18%, and the combination by 78%. In addition, the drugs individually and in combination had similar inhibitory effects on JDF-1 spermidine content. One of the unexpected findings was the alteration in the spermine:spermidine ratio in the tumors treated with the combination of DFMO and IFN-alpha 2. The ratio in this group decreased to 0.44, while ratios for control, IFN-alpha 2 only, and DFMO only were 0.99, 0.66, and 0.88, respectively. These results clearly show that combined therapy with DFMO and IFN-alpha 2 is more effective than is single-drug therapy. The mechanism by which these drugs coordinately inhibit tumor growth is unclear but appears to be associated with direct inhibition of tumor cell proliferation, possibly by modulation of polyamine metabolism.

Seasonal rhythm of platelet 3H-imipramine binding in normal controls.

The densities of platelet 3H-imipramine sites were determined by repetitive measures of 11 normal controls over the course of 1 year. A significant seasonal variation was found, with a circannual peak on February 17 and a nadir on August 18. The estimated amplitude of this rhythm was +/- 599.54 fmol/mg, which fluctuated about a yearly mean of 2647.5 fmol/mg. The present results underscore the importance of including seasonally matched controls in the evaluation of potential patient differences in platelet binding.

Polyadenylation of ribosomal RNA by Candida albicans.

Candida albicans is the leading fungal pathogen in immunocompromised patients such as those with AIDS and malignancies. It is a polymorphic organism existing as a unicellular yeast or as filamentous forms that include pseudohyphae and true hyphae. While studying the early period of hyphal transformation, comparing cDNAs from yeast to those in early transition, we were surprised to find 25S rRNA represented frequently in our differential display assays, suggesting that our reverse transcription with poly-T primers was copying rRNA with extended poly-A 3' ends. We now report that both the yeast forms and germinating organisms polyadenylate some of their 25S rRNA transcripts. We also found a rapid and transient enhancement of this process upon stimulation with serum. These data indicate that 25S rRNA polyadenylation is part of the biological repertoire of C. albicans and its transient upregulation just prior to hyphal development raises the possibility of a regulatory role in this transition.

Expression of the Leishmania tarentolae ubiquitin-encoding and mini-exon genes.

To develop models for transcription and trans-splicing in kinetoplastid protozoa, we have characterized ubiquitin (Ubi) gene organization and mRNA processing in Leishmania tarentolae (Lt). Three ubi loci were characterized: two discrete Ubi-extension protein 52 (EP52)-encoding genes (ubiA and ubiB) and a polymorphic polyubiquitin-encoding gene (ubiC). The three loci resided on chromosomes of 2.05 Mb, 630 kb and 2.9 Mb, respectively. On the basis of upstream flanking gene identity, ubiB appears to be the homologue of the tandemly repeated ubi-EP52/1 and 2 in Trypanosoma brucei (Tb). Similar to Trypanosoma cruzi, Lt did not contain a homologue of the ubi-EP76 that has been found in Saccharomyces cerevisiae and multicellular organisms. All three Lt ubi loci were transcribed. The primary transcripts from the ubi loci were processed at the 5'-end by trans-splicing with the mini-exon. A Lt mini-exon gene (min) that gave rise to a 95-nt primary transcript, which is the second template in the trans-splicing reaction, was also characterized.

Opsonic activity of MCP-1 and MCP-2, cationic peptides from rabbit alveolar macrophages.

MCP-1 and MCP-2, cationic peptides derived from rabbit alveolar macrophages, enhanced the ability of these cells to ingest Staphylococcus aureus, Klebsiella pneumoniae, Bordetella bronchiseptica, and Candida albicans in vitro. The opsonic effect of MCP-1 was potentiated by Ca++ and Mg++ and was associated with binding of the peptide to alveolar macrophages and microorganisms. MCP-1 and MCP-2 may contribute to the ability of alveolar macrophage to ingest microorganisms that gain entry to the lower respiratory tract.

Identification of a gp63 surface glycoprotein in Leishmania tarentolae.

The promastigote stage of most if not all Leishmania species possesses an abundant surface glycoprotein of 63 kDa (gp63) that has protease activity. We show that the lizard parasite Leishmania tarentolae appears to lack the surface protease activity. L. tarentolae does, however, possess an approximately 63-kDa molecule that is antigenically cross-reactive with the L. major gp63. Additionally, the genome of L. tarentolae contains sequences that hybridise at high stringency to a L. major gp63 gene probe.

Intracavernous pressure responses to physical and electrical stimulation of the cavernous nerve in rats.

OBJECTIVES: To better define the techniques of nerve-sparing prostate dissection that would result in preservation of erectile function, we characterize the effects of physical pressure on the prostate and cavernous nerve, electrical stimulation of the cavernous nerve, and pharmacologic manipulations on intracavernous pressure (ICP) in normal and diabetic rats. METHODS: Fischer-34 rats, both normal and diabetic, underwent dissections that isolated the cavernous bodies and cavernous nerves. Cavernous body pressures were characterized during surgical manipulation, during electrical stimulation of the cavernous nerves, and following papaverine hydrochloride injection. RESULTS: In normal rats, baseline cavernous pressures ranged from 5 to 15 cm H2O (mean 12.29). In diabetic rats, the baseline pressure was significantly lower (3 to 7.5 cm H2O). Lateral nerve displacement caused ICP to rise to approximately 35 cm H2O in normal rats, but only to 20 cm H2O in diabetic rats. Electrostimulation resulted in cavernous pressure increases of 10-fold from baseline in normal rats and sevenfold from baseline in diabetic rats. ICPs were not disturbed appreciably with nerve-sparing dissection techniques. Neurotomy resulted in declines in baseline cavernous pressures in all rats. Electrostimulation of the distal end of a severed nerve resulted in pressure rises to 50% of those observed in rats with intact cavernous nerves. Intracavernous papaverine injection before or after nerve stimulation masked subsequent (expected) pressure changes. CONCLUSIONS: A change in cavernous pressure is a sensitive indicator of cavernous nerve manipulation. Both cavernous pressure measurements and electrostimulation of cavernous nerves may aid surgeons during radical prostatectomy.

Intravesical bacille Calmette-Guérin therapy for muscle invasive bladder cancer.

OBJECTIVES: This investigation attempted to determine whether the degree of fibronectin expression in the bladders of patients with invasive transitional cell carcinoma correlated with their clinical response to intravesical bacille Calmette-Guerin (BCG) therapy. METHODS: Following transurethral resection of all invasive disease, 13 patients with Stages T2-T4 bladder cancer were administered intravesical BCG (fo 6 weeks followed by monthly instillations). Fibronectin expression in the patients' resected tumors and normal mucosa was determined by immunohistochemical staining techniques. Minimum disease-free follow-up was 60 months. RESULTS: Only 1 of 13 patients had neither local nor systemic disease recurrence; 10 of 13 patients developed systemic disease and 7 patients died from metastases. Fibronectin expression was not correlated with the clinical response to BCG. CONCLUSIONS: Intravesical BCG therapy for the treatment of muscle invasive transitional cell carcinoma of the bladder is ineffective. Fibronectin expression in the bladder of patients with invasive disease is variable and does not correlate significantly with the clinical response to BCG therapy.

Synchronous, primary bilateral lymphoma of testes.

Lymphoma of the testicle is the most common testicular neoplasm in men over sixty years of age, but usually represents a secondary manifestation of systemic disease. This case report describes the rare phenomenon of a synchronous, primary bilateral lymphoma of the testes (Stage Ie) occurring in a sixty-eight-year-old man.

Combined laparoscopic pelvic lymph node dissection and modified belt radical perineal prostatectomy for localized prostatic adenocarcinoma.

OBJECTIVE: Despite many known advantages, the radical perineal prostatectomy (RPP) had fallen out of favor because of the need for a second incision for the regional lymph node dissection. Laparoscopic lymphadenectomy, however, provides an accurate and minimally invasive alternative to open lymph node dissection. Herein are reported the practical advantages of combining laparoscopic lymph node dissection (LPLND) with RPP. METHODS: Forty-nine patients with clinically localized carcinoma of the prostate were considered candidates for RPP using a modified Belt technique. Thirty-five patients underwent attempted LPLND and 31 of these patients subsequently underwent RPP; 14 patients underwent RPP alone. Variables examined included total operative time, transfusion requirement, length of hospital stay, continence, and potency. RESULTS: The mean operative time for LPLND combined with RPP in 31 patients, including time for repositioning, was 4.5 hours (range 3.0 to 7.0 hours). Only 26 percent of the patients who underwent the combined approach required blood transfusions of which 75 percent received autologous units. Mean length of stay was six days, and laparoscopy did not contribute significantly to postoperative morbidity. Eighty-four percent of the patients are completely continent. Of 27 potent patients who underwent nerve-sparing surgery, 22 percent are potent and an additional 30 percent are sexually active with intracavernous pharmacotherapy. There were no perioperative deaths, 2 major complications, and 5 minor complications. CONCLUSIONS: Laparoscopic techniques now permit the urologist to utilize the perineal approach, and its many advantages, to radical prostatic extirpation without the need for a formal abdominal incision. The minimal blood loss and low morbidity associated with laparoscopic pelvic lymphadenectomy combined with the radical perineal prostatectomy make this procedure an attractive alternative to the open retropubic approach for clinically localized prostatic adenocarcinoma.

Renal cell carcinoma: considerations for nephron-sparing surgery.

OBJECTIVES: The performance of nephron-sparing surgery in patients with a normally functioning contralateral kidney is controversial. To explore the risk factors that may contribute to the success or failure of nephron-sparing surgery, we examined the radiology and pathology reports of 278 patients who underwent radical nephrectomy for the treatment of clinically localized renal cell carcinoma. METHODS: We collated patient data from the records of 278 patients with Stage III renal cell carcinoma entered into the Eastern Cooperative Oncology Group protocol EST 2886 and compared preoperative clinical staging with postoperative pathologic results. Patients were considered potential candidates for nephron-sparing surgery if their preoperative radiographic studies indicated that the carcinoma was a single polar lesion 5 cm or less in diameter. RESULTS: Of 278 radical nephrectomy specimens, 36 had primary lesions 5 cm or less in diameter. Preoperative radiographic studies showed 14 of 36 would not have been considered eligible for nephron-sparing surgery. Of the remaining 22 potential candidates, pathologic studies showed multifocal lesions in 11, renal vein disease in 4, and nodal disease in 2. Only 5 of 22 patients might have had specimen-confined disease (T3a lesion). CONCLUSIONS: Capsular-penetrating (T3a) renal cell carcinoma is not often appreciated preoperatively and is associated frequently with multifocal lesions, renal vein or nodal disease. Frozen section studies to rule out T3a disease at the time of nephron-sparing surgery may help determine which patients need radical surgery.

Clinicopathologic correlation of lipidization and detachment of the retinal pigment epithelium.

A 49-year-old woman had a few small drusen-like lesions and one larger area of depigmentation in the right fundus. The pin-point lesions corresponded to single enlarged retinal pigment epithelial cells with lipid accumulation and the larger area represented a small, localized retinal pigment epithelial detachment (soft druse). Lipoidal degeneration of individual retinal pigment epithelial cells may be a mechanism of nodular drusen formation. The soft druse was associated with thickening of the basement membrane of the retinal pigment epithelium.

Calcium channel antagonists in the treatment of interstitial cystitis.

The calcium channel antagonist nifedipine has shown efficacy in the treatment of interstitial cystitis and the urethral syndrome. The optimal daily dose of nifedipine can be determined with the use of a nifedipine titration test. To complete the repair of damaged bladder and/or urethral mucosa, nifedipine therapy should be used for a minimum of 3 months. Patients who do not respond well to nifedipine are those with the pelvic floor muscle spasm syndrome variant of interstitial cystitis.

Management of recurrent penile cancer following partial or total penectomy.

The initial management of localized penile carcinoma determines the probability of recurrence. Although potentially disfiguring, the management of recurrent carcinoma of the penis requires aggressive surgical resection of both the primary lesion and nodal sites to effect the best chance for long-term survival.

Successful treatment of spinal arachnoiditis due to coccidioidomycosis. Case report.

An unusual case is reported of a patient with spastic paraparesis who was found to have severe spinal arachnoiditis due to Coccidioides immitis. Despite an obstructive hydrocephalus and a spinal subarachnoid block, the patient was treated effectively with surgery (shunting) and antifungal therapy (amphotericin and ketoconazole). He remains asymptomatic 3 years after diagnosis. Aggressive surgical and medical treatment of coccidioidal infection of the central nervous system can be beneficial, even in patients with the worst prognosis.

Biologic response modifiers and urologic malignancies.

Biologic response modifiers represent a new generation of immunotherapeutic agents. Although biologic response modifiers such as interferon have been moderately successful in treating B-cell malignancies, they have not been as successful for the management of advanced genitourinary malignancies. The measurement of biologic response modifiers in the urine may prove useful for directing intravesical BCG therapy for the treatment of superficial bladder cancer or for directing the use of prophylactic antibiotics for the management of urinary tract infections.

Measurement and partial characterization of an interleukin-2 inhibitor (IL-2-IN) in human urine.

We observed a human urine-derived protein complex (IL-2-IN) which competitively inhibits interleukin-2 (IL-2) dependent murine lymphocyte proliferation. Measurements of urinary IL-2-IN have been used to stratify the immune response of patients to bacteria in the bladder. Partial characterization of IL-2-IN indicates that it is a heat-stable, 75 kDa complex comprised of interleukin-2 bound to another protein(s). Although the IL-2-IN complex is stable in physiologic buffers, the complex can be disrupted using acidic or low-ionic strength buffers, thereby liberating IL-2. IL-2-IN activity is susceptible to bacterial and endogenous urinary proteolysis. The IL-2 bound in the IL-2-IN complex cannot be detected using a double monoclonal antibody radioimmunoassay for IL-2. Unlike other IL-2 binding proteins, the IL-2 binding protein of the IL-2-IN complex is not a soluble interleukin-2 receptor. A modification of the bioassay for interleukin-2 activity is the method of choice for the detection and quantification of urinary IL-2-IN.

Primary Candida meningitis and chronic granulomatous disease.

The occurrence of two rare entities in a single patient can be fortuitous or may signify some deeper relationship. A young boy was recently treated for primary Candida meningitis. Autopsy findings suggested to an experienced pathologist the presence of chronic granulomatous disease (CGD), unrecognized during his life. The patient's identical twin brother was tested and found to have the typical laboratory features of CGD. The literature on Candida meningitis was reviewed and 15 cases were discovered that apparently arose in the absence of recognized predisposing causes. All but one of these cases occurred in males, and most occurred during the first three decades of life. The case reports and literature review presented herein suggest that CGD should be suspected when a case of "primary" Candida meningitis is encountered.