Biomedical subjects
Publications and source records attributed to J E Wright.
Congenital absence of scrotal skin is extremely rare and no reports can be found in the literature. Few experienced pediatric surgeons have seen a case and no method of creation of a scrotum has been described. A patient with this condition is described, together with a method of construction of a scrotum from preputial skin.
A case of anaerobic orbital cellulitis secondary to intraorbital wood and an approach to management are presented. Retained foreign bodies should be suspected in all penetrating orbital injuries involving wood. Computed tomography (CT) should be performed to delineate the location and size of any foreign body and to determine damage to adjacent structures. Magnetic resonance imaging (MRI) is useful in certain circumstances. Orbital infection should be anticipated and broad-spectrum antibiotic cover (including anaerobes) provided. Surgical intervention should be undertaken to remove any retained foreign bodies to prevent vision-threatening complications.
Periorbital dermoid cysts should be removed because they commonly leak their irritant contents into the surrounding tissues. The underlying bone may, however, be involved in patients with dermoid cysts at the outer canthus. Computed tomography studies of 70 patients (43 men and 27 women, aged 30 months to 63 years, mean 29 years) with proved dermoid cysts of this type were reviewed. The lesion was always unilateral; 34 were on the left. The bone of the lateral wall and superotemporal angle of the orbit showed the following abnormalities, often in combination: pressure erosion in 61 cases and an otherwise abnormal shape, probably developmental, in 55; the dermoid cyst entered a tunnel or canal through the lateral wall in 24; a blind pit or crater in 15; and a cleft in 20; many patients also showed abnormal bone texture. These findings are extremely important for planning adequate surgery, and indicate that bony involvement is much more frequent than previously appreciated.
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Seven patients with a mean age of 65 years (range 50-76 years) who had minor aortic valve gradients (less than 25 mmHg) at preoperative cardiac catheterization underwent coronary artery bypass surgery without aortic valve surgery, but required a second operation for aortic valve replacement between five and nine years later because of symptomatic aortic valve stenosis with a valve gradient which had increased to between 60 and 100 mmHg. Serial hemodynamic observations in patients with aortic stenosis have demonstrated that the rate at which stenosis progresses is widely variable. However, replacement of aortic valves at the time of initial coronary artery surgery may subject the patients to an increased risk of operative mortality and prosthetic valve-related complications. On the other hand, the patient may miss the opportunity to obtain maximum benefit from valve replacement before deterioration of left ventricular function, particularly in the presence of coronary artery disease, and there are also the risks of resternotomy. We are currently inclined to replace the aortic valve in coronary patients with asymptomatic aortic stenosis, but our experience is not sufficient to draw final conclusions and the relevant literature does not provide a clear guidance. The aim of this publication is to expose this dilemma.
Although the mechanisms of resistance to methotrexate (MTX) are known in experimental tumors made resistant to this drug, little information is available regarding acquired resistance to MTX in patients. A competitive displacement assay using the fluorescent lysine analogue of MTX, N-(4-amino-4-deoxy-N10-methylpteroyl)-N epsilon-(4'-fluorescein-thiocarbamyl)-L-lysine (PT430), was developed as a sensitive method of detection of transport resistance to MTX in cell lines, as well as in blast cells from patients with leukemia. Rapid uptake of PT430 at high concentrations (20 mumol/L) in leukemic blasts resulted in achievement of steady-state levels within 2 hours. Subsequent incubation with the folate antagonists, MTX and trimetrexate (TMTX), which differ in the mode of carrier transport, produced characteristic patterns of PT430 displacement. Flow cytometric analysis of the mean fluorescence intensity in the human CCRF-CEM T-cell lymphoblastic leukemia cell line and its MTX-resistant subline clearly identified the presence of transport deficiency in the resistant subline. Analysis of blasts from 17 patients with leukemia, nine with no prior chemotherapy and eight previously treated with chemotherapy, found evidence of MTX transport resistance in two of the four patients who were treated with MTX and considered to be clinically resistant to the drug. The finding that blast cells of some patients with leukemia considered clinically resistant to MTX is due to decreased MTX transport has important implications for clinical use of this drug and for new drug development.
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We have studied the discrepancy in the degree of methotrexate (MTX) resistance that exists between two clonal cell lines, mouse 3T6 R50 cells and Chinese hamster ovary B11 0.5 cells that overexpress comparable levels of dihydrofolate reductase, yet exhibit a 100-fold difference in MTX resistance while maintaining similar sensitivity to the lipophilic antifolates trimetrexate and piritrexim. These data suggested that R50 cells may possess additional mechanism(s) of antifolate resistance, such as MTX transport alteration. Flow cytometric analysis using fluorescein methotrexate revealed comparable levels of fluorescein MTX displacement with lipophilic antifolates in viable R50 and B11 0.5 cells, but marked insensitivity of R50 cells to MTX competition, thus suggesting a poor uptake of MTX into R50 cells. Analysis of the kinetic parameters of dihydrofolate reductase from R50 cells neither showed alterations in enzyme affinities for various antifolates nor in the Michaelis constant for folic acid and NADPH nor a change in the pH activity optimum. R50 cell-free extracts contained wild-type levels of folylpoly-gamma-glutamyl synthetase activity. However, following metabolic labeling with [3H]MTX, no MTX polyglutamates could be detected in R50 cells. We conclude that the high level of MTX resistance in R50 cells is multifactorial, including overexpression of dihydrofolate reductase, reduced MTX transport, and possibly altered formation of MTX polyglutamates. The potential interactions between the different modalities of MTX resistance in R50 cells are being discussed.
Orbital haemangiopericytomas are ideally managed by complete surgical excision in the first instance. This is frequently not achieved, because difficulty in making the diagnosis preoperatively results in incisional biopsy and the highly vascular nature of the tumour makes complete excision difficult. A series of 12 patients with orbital haemangiopericytoma seen over a 23-year period is presented. The following combination of clinical and radiological features is suggestive of haemangiopericytoma. 1. Painless non-axial proptosis with downward displacement of the globe. 2. Intermittent upper lid swelling. 3. A soft, superiorly located mass with poorly defined borders, especially with a blue hue. 4. A superiorly located, rounded or elongated extraconal mass on CT, isodense with brain, with smooth, well-defined borders and moderate to marked enhancement with the injection of intravenous contrast medium. 5. Significant blush in all three phases of carotid angiography, without prominent arteriovenous shunting. Once haemangiopericytoma is suspected, complete surgical excision is recommended.
Orbital chondrosarcomas are extremely rare and are usually an extension of tumours involving the paranasal sinuses. A unique case of dedifferentiated chondrosarcoma arising solely within the orbit is presented.
Orbital cavernous haemangioma, a common orbital tumour, is usually single and unilateral. We report the first case of histologically confirmed bilateral multiple cavernous haemangiomas of the orbit.
To reduce the risk of recurrence and malignant transformation, pleomorphic adenomas of the lacrimal gland should be removed intact, without prior biopsy. Seventy one of the 78 patients in this series were referred without previous surgery, and, on clinical or radiological evidence, 63 (89%) tumours were correctly diagnosed and totally excised, with preservation of a margin of the surrounding normal tissue. Sixty three patients had tumour within the body of the gland and 55 (84%) had radiological signs or satisfied clinical criteria for pleomorphic adenoma that we suggested previously; that is, over 1 year of symptoms and absence of pain. Eight (16%) orbital lobe tumours were misdiagnosed preoperatively and biopsied; in all these patients symptoms had been present for less than 1 year, and four patients had pain. Eight patients with tumours arising in the palpebral lobe had a short history of an upper lid mass, and their tumours were excised without biopsy. With the surgical techniques described in this paper, there has been no recurrence of tumour in patients with follow-up as long as 21 years. A modification of surgical technique, with preservation of the palpebral lobe of the gland, has reduced the incidence of postoperative dry eye and distortion of the upper eyelid.
The clinical characteristics and outcome of 50 primary malignant neoplasms of the lacrimal gland are reviewed: 38 (76%) adenoid cystic carcinomas, six (12%) carcinomas arising in pleomorphic adenoma, and six (12%) adenocarcinomas or other types of carcinoma. Most patients presented with a short history and pain, though pain tended to occur less often and later with adenocarcinoma than with adenoid cystic carcinoma. Pain was unrelated to the duration of symptoms, invasion of bone, loss of trigeminal nerve function, or the frequency and time of tumour recurrence. The estimated disease-free survival for patients with adenoid cystic carcinoma was significantly (p less than 0.01) reduced where half or more of the biopsy specimen showed basaloid differentiation. Eleven patients underwent extended cranio-orbital resection, and the others received a combination of total dacryoadenectomy adenectomy and/or radiotherapy. Survival after adenoid cystic carcinomas appears to be significantly (p less than 0.05) greater when tumour resection is combined with radiotherapy than after radiotherapy alone. At present, however, the rate of disease-free survival after treatment of adenoid cystic carcinoma appears unaltered by cranio-orbital resection, though these latter patients form a relatively greater proportion of those surviving for more than 10 years. Further long-term follow-up is needed to see if this technique does influence survival.
Actinomycosis is a very rare cause of orbital abscess usually attributable to direct spread from adjacent structures. A case of actinomycosis of the orbit is presented, which was treated as orbital pseudotumour for 3 months before progression of signs and symptoms, despite high dose steroids, led to the diagnosis being reconsidered.
BACKGROUND: Cyclophosphamide, which forms the nucleus for virtually all preparative regimens for autologous bone marrow transplantation (ABMT), is an alkylating agent of which cytotoxicity is not directly caused by the parent compound but by its biologically active metabolites. Its nonmyelosuppressive toxicity in the ABMT setting is cardiomyopathy. We attempted to determine any correlation between plasma levels of total cyclophosphamide and the subsequent development of cardiac dysfunction. PATIENTS AND METHODS: Analyses of plasma levels and the derivation of plasma concentration-time curves (area under the curve [AUC]) were performed in 19 women with metastatic breast carcinoma, who received a continuous 96-hour infusion of cyclophosphamide, thiotepa, and carboplatin (CTCb) with ABMT. The assay for total cyclophosphamide measures the inactive parent compound; reliable assays of the active metabolites of cyclophosphamide are not yet available. RESULTS: Six of 19 women developed moderate, but transient, congestive heart failure (CHF) as assessed by clinical and radiologic criteria. These patients had a significantly lower AUC of total cyclophosphamide (median, 2,888 mumol/L/h) than patients who did not develop CHF (median, 6,121 mumol/L/h) (P less than .002). Median duration of tumor response in these patients was also more durable; at least 22 months in patients with lower AUCs versus a median of 5.25 months in those with higher AUCs (P = .008). CONCLUSION: These pharmacokinetic data support the premise that enhancement of cyclophosphamide activation may lead to both greater tumor cytotoxicity and increased but reversible end-organ toxicity. Early analysis of pharmacokinetic data may allow modulation of cyclophosphamide administration in an attempt to enhance therapeutic efficacy.
The use of anabolic-androgenic steroids (AS) to enhance appearance as well as physical/physiological capacities has increased dramatically over the past four decades in all age groups from early adolescence to adulthood. Although higher AS use rates are reported by elite and competitive athletes, a significant number of recreational athletes appear to be using AS. The scientific literature is inconsistent and at times at odds with the conventional wisdom and empirical experiences of the athletic community regarding the ergogenic effects of AS. However, individuals experienced in weight training, with an adequate diet, and who continue training during AS administration seem to consistently increase their strength and lean mass over what would have been expected from training alone. Previous research documenting deleterious but transient and mostly asymptomatic acute changes in physiology, risk factors and behavior has been inconclusive regarding the long term health impact. The abuse of AS constitutes a special challenge to society. AS are not euphorigenic or mood altering immediately following administration, as are other illicit drugs; the appetite for AS has been created predominantly by our societal fixations on winning and physical appearance. Consequently any successful intervention in this area must go beyond education, law enforcement and drug testing, and attempt to change a social environment which currently encourages the use of AS.
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