R 75251, a new inhibitor of steroid biosynthesis

R 75251, a new imidazole derivative, inhibited the conversion of androgens to estrogens, of progestins to androstenedione and testosterone, and of 11-deoxycorticosterone to corticosterone in human placenta microsomes, subcellular fraction of rat testis, bovine adrenocortical mitochondria, in cultured rat granulosa, testicular and adrenal cells, respectively. In vitro, no effect on cholesterol synthesis and cholesterol side-chain cleavage was found at concentrations up to 10 microM. In rat granulosa cells, no effect on progesterone production was detected. In vitro, no effect on steroid radioligand binding was observed. In male volunteers, a single dose of 300 mg of R 75251 significantly lowered plasma testosterone and estradiol for 24 hours and increased plasma concentration of 17 alpha-hydroxyprogesterone and progesterone. As compared with ketoconazole high dose (600 mg b.i.d), R 75251 (300 mg b.i.d) was at least as efficacious as inhibitor of testosterone synthesis when studied during ACTH stimulation. In contrast to ketoconazole, R 75251 did not significantly affect circulating adrenal androgen levels in male volunteers. Precursors of gluco- and mineralocorticoids such as 11-deoxycortisol and 11-deoxycorticosterone accumulated more than after ketoconazole administration. The data show that the cytochrome P450-dependent aromatase, 17-hydroxylase/17,20-lyase, and 11-hydroxylase are the target enzymes for R 75251.     

Non-ulcerative fungal keratitis diagnosed by posterior lamellar biopsy*

We report a case of Fusarium solani keratitis which highlights the difficulties often associated with management of fungal corneal infections. This case demonstrates several unusual and interesting features: the occurrence of deep fungal pathology after superficial injury, the difficulties encountered in attempting to isolate and identify the causative organism, and the protracted course taken by an organism often noted to be rapidly destructive. These features necessitated an individual approach to therapy, employing unconventional medical and surgical techniques to achieve a satisfactory outcome     

Transplantation of the cornea.

Corneal transplantation is the most widely practised form of allografting in clinical practice. The operation is used to correct developmental abnormalities of corneal shape such as keratoconus, to overcome opacities of the cornea, to relieve pain and to mend perforations. Corneal transplantation is generally successful but contrary to popular belief, corneal grafts can be rejected. This is a particular problem for patients treated for the sequelae of inflammatory disease. The relative importance of measures such as systemic immunosuppression and tissue typing is less in corneal transplantation than in other forms of clinical allografting. Overcoming rejection, achieving the best optical configuration in a graft, and increasing the number of donor corneas available for transplantation represent the main avenues for achieving improvements in corneal transplantation.     

HMPAO Single-Photon Emission Computed Tomography in Posterior Circulation Infarcts

The sensitivity of single-photon emission computed tomography (SPECT) in evaluating posterior mculation infarcts compared with that of computed tomography (CT) or magnetic resonance imaging (MRI) remains unknown. In a hospital-based population, the authors studied SPECT, CT, and MRI in 35 consecutive patients presentmg with acute infarction clinically localized in the thalamus (7), posterior cerebral artery (PCA) territory (15), bramtem (19), and cerebellum (3) Multiple infarcts were noted m 8 patients. Overall, the SPECT sensitivity was lower than that of MRI (21% vs 93%, p ~ 0 004) and CT (42% vs 65%, p = 0 046) The SPECT and CT sensitivities were not Significantly different (67% vs 73%) for PCA Infarcts. Performed within 24 hours, SPECT showed a relevant hypoperfusion in all PCA mfarcts. For brainstem infarcts, CT (33%, p = 0 074) and MRI (91 %, p = 0.004) were more sensitive than SPECT, which showed no hemispheric hypoperfusion. The sensitivity of the three imaging techniques was 100% for large cerebellar infarcts. For the small group of thalamic infarcts, the SPECT, CT, and MRI sensitivities were 14, 71, and 100%, respectively. Thus, SPECT compared to CT and MRI is not helpful in the subacute phase to localize PCA and cerebellar infarcts and is of limited value for thalamic infarcts. In the first hours, the absence of cerebral hypoperfusion in brainstem mfarcts may help to differentiate them from hemispheric infarcts usually associated with profound hypoperfusion.     

Laparoscopic partial fundoplication vs laparoscopic Nissen-Rosetti fundoplication

Background: Since 1992, all patients at our institution who have met standard accepted criteria for surgical intervention for complicated gastroesophageal reflux disease have been entered into a prospective sequential clinical study to evaluate outcomes of the laparoscopic approach to the Nissen-Rosetti procedure and a modified Toupet procedure. Methods: A standardized workup with upper GI series, esophagography, and endoscopy was used in all patients. Manometry, pH testing, and other special tests were used selectively. A measuring technique was used to determine wrap size without the use of dilators. The short gastric vessels were left intact in all patients. A cosurgeon approach was used, with technical factors described herein. Results: Some 226 of 231 cases were completed laparoscopically (98%)—125 patients in the Nissen-Rosetti group and 101 in the partial fundoplication group. There were no clinical failures in either group. The partial fundoplication group performed better than the Nissen-Rosetti group in all categories of comparison. Return to normal eating habits was much earlier in the partial wrap group (p < 0.0001). Postop distal esophageal sphincter pressures in the two groups were equal at 15 mmHg. Eight patients suffered significant dysphagia requiring endoscopy and dilatation, all in the Nissen-Rosetti group (p < 0.01). Minor complications occurred in 12% of the total group. There was a total surgical revision rate of 3%. There were no gastric or esophageal perforations. Average operative time was 30 min. Average hospital stay was 1.4 days. Hospital charges for the laparoscopic approach averaged $6,000 dollars compared to $12,000 for the open approach. Conclusion: Laparoscopic partial fundoplication is as effective as laparoscopic Nissen-Rosetti fundoplication, with a higher satisfaction rate and fewer side effects. Measuring for wrap and hiatus size eliminates the need for and risk of using stiff dilators. By utilizing cosurgeons and currently available technology, cost, operative time, hospital time, and complications can be reduced to a finite minimum. Received: 12 December 1995/Accepted: 12 August 1996     

Aromatization of androgens is important for skeletal maintenance of aged male rats

A nonsteroidal aromatase inhibitor vorozole (VOR) was administered to aged (12 months old) male Wistar rats and its effect was compared with the effect of androgen deficiency. The rats were either sham-operated (SHAM) or orchidectomized (ORCH) and treated with or without VOR. Thus, four experimental groups were created (SHAM, ORCH, SHAM + VOR, ORCH + VOR). The follow-up period was 4 months. At the end of the experimental period, bone mineral density (BMD) of the first four lumbar vertebrae and right femur was measured ex vivo with dual-energy X-ray absorptiometry, bone formation was evaluated by serum osteocalcin, and bone resorption by urinary excretion of (deoxy)pyridinoline. Orchidectomy increased bone resorption 2- to 3-fold whereas bone formation was only slightly increased. Treatment of intact male rats with VOR also increased bone resorption (+30% increase) whereas bone formation was not increased in this SHAM + VOR group. Their BMD was 7% lower in the femur (P < 0.01) and 6% lower in the lumbar vertebrae (P < 0.01) compared with the SHAM group that had not received VOR. Moreover, this decrease of bone mineral density was not significantly different from the expected decrease of bone density observed in the ORCH groups (6–10%). This was also reflected by a decrease of calcium content of the first four lumbar vertebrae of 15% (P < 0.001) in the SHAM + VOR group and 9–14% (P < 0.05) in the ORCH groups compared with the SHAM group, respectively. These data therefore suggest that inhibition of aromatization of androgens into estrogens increases bone resorption and bone loss similar to that observed after complete removal of androgens. Aromatization of androgens into estrogens may therefore, at least partly, explain the effects of androgens on skeletal maintenance. Received: 13 October 1995 / Accepted: 23 February 1996     

A practical approach to interpretation of corneal specimens

Corneal specimens form only a small part of the routine practice for most histopathologists but their assessment often requires considerable effort and specialized knowledge. The most common corneal specimens, full-thickness corneal discs and corneal biopsies, are discussed in this review. Corneal discs removed at keratoplasty are non-urgent specimens, as definitive treatment has already been undertaken, and while the pathologic diagnosis may change the prognosis for the graft, it rarely affects immediate treatment. Accurate diagnosis is still important, and will affect counseling of the patient, but referral to a colleague with a special interest is possible if necessary. Conversely, small partial-thickness corneal biopsies, which are mostly undertaken for culture negative keratitis with underlying suspected infection, are very urgent. Infectious keratitis can follow an extremely aggressive course, resulting in destruction of the cornea within hours. Accurate diagnosis is imperative. Due to the urgency of such specimens and the importance of diagnosis for immediate treatment, referral is not usually possible. It is the role of the pathologist to make optimal use of a small specimen to reach the relevant diagnosis in the minimum space of time.