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.     

Repair of large midline incisional hernias with polypropylene mesh: Comparison of three operative techniques

Polypropylene mesh is widely used for the reconstruction of incisional hernias that cannot be closed primarily. Several techniques have been advocated to implant the mesh. The objective of this study was to evaluate, retrospectively, early and late results of three different techniques, onlay, inlay, and underlay. The records of 53 consecutive patients with a large midline incisional hernia — 25 women and 28 men, mean age 60.4 (range 28–94) — were reviewed. Polypropylene mesh was implanted using the onlay technique in 13 patients, inlay in 23 patients, and underlay in 17 patients. Either the greater omentum or a polyglactin mesh was interponated between the mesh and the viscera. The records of these 53 patients were reviewed with respect to: size and cause of the hernia, pre- and postoperative mortality and morbidity, with special attention to wound complications. Patients were invited to attend the outpatient clinic at least 12 months after implantation of the mesh for physical examination of the abdominal wall. Postoperative complications occurred in 14 (26.4%) patients. The onlay technique had significantly more complications, as compared to both other techniques. Reherniation occurred in 15 (28.3%) patients. The reherniation rate of the inlay technique was significantly higher than after the underlay technique (44% vs 12%, P=0.03) and tended to be higher than the onlay technique (44% vs 23%, P=0.22). Repair of large midline incisional hernias with the use of a polypropylene mesh carries a high risk of complications and has a high reherniation rate. The underlay technique seems to be the better technique.     

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.     

Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia

The authors report the clinical and laboratory findings of a patient who had severe immune hemolytic anemia due to hydrochlorothiazide (HCTZ). In this case, the HCTZ antibody reacted not only with other thiazide and thiazide-like drugs, but also with a chemically unrelated diuretic, ethacrynic acid. These results indicate that HCTZ antibody activity is not restricted solely to the thiazides and imply that therapy with any of the reactive drugs would be contraindicated for this patient. The serologic screening for drug reactivity may be useful for selecting alternative therapy for patients with drug-induced immune hemolytic anemia.     

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