Mosaic pathogenic variants in AKT3 cause capillary malformation and undergrowth

Capillary malformations are slow-flow vascular malformations that affect the microcirculation including capillaries and post capillary venules and can be associated with growth differences. Specifically, the association of capillary malformations with undergrowth is a vastly understudied vascular syndrome with few reports of genetic causes including PIK3CA, GNAQ, and GNA11. Recently, a somatic pathogenic variant in AKT3 was identified in one child with a cutaneous vascular syndrome similar to cutis marmorata telangiectatica congenita, undergrowth, and no neurodevelopmental features. Here, we present a male patient with a capillary malformation and undergrowth due to a somatic pathogenic variant in AKT3 to confirm this association. It is essential to consider that mosaic pathogenic variants in AKT3 can cause a wide spectrum of disease. There is a need for future studies focusing on capillary malformations with undergrowth to understand the underlying mechanism.     

Reproducible X-ray projection geometry in edentulous patients

OBJECTIVE: To evaluate a novel fixation system for reproducible radiography in edentulous patients. METHODS: A conventional extra-oral fixation system was modified with a filmholder and adjustable scales. For measuring reproducibility and angulation errors two rods and two balls were fixed on the alveolar crests of the maxilla and the mandible and angular variations were measured. One hundred radiographs of a conventional phantom were taken by one of the authors and by ten dental students. The angular disparity was calculated and intra- and interoperator precision determined. RESULTS: The average time taken to assemble the fixation system was 4 min. The 95% confidence interval for precision of the single operator was less than 2.5 degrees in both the maxilla and mandible. The 95% confidence interval for precision of the ten students was less than 2.2 degrees for the maxilla and 2.7 degrees for the mandible. There was no significant difference (P>0.05) in interoperator precision. CONCLUSION: The novel extra-oral fixation system appears to be a potential means of obtaining reproducible radiographs of edentulous patients.     

Randomized clinical trial of the 350-mm2 versus the 500-mm2 Baerveldt implant: longer term results: Is bigger better?

OBJECTIVE: To report the longer term results of a randomized, clinical trial comparing the 350-mm2 and the 500-mm2 Baerveldt glaucoma implants. DESIGN: Extended follow-up on a randomized, controlled trial. PARTICIPANTS: Between March 1991 and April 1993, 107 patients with uncontrolled intraocular pressure (IOP) due to non-neovascular glaucoma associated with aphakia, pseudophakia, or failed filters were randomly assigned for surgical placement of either the 350-mm or the 500-mm2 Baerveldt implant at the Doheny Eye Institute. METHODS: A random-numbers table was used to assign each patient to one of the two groups. Preoperative IOPs and visual acuities were recorded. Clinical records were reviewed to ascertain postoperative IOPs, visual acuities, number of medications used, and implant-related complications that occurred throughout the follow-up period. MAIN OUTCOME MEASURES: Success was defined as IOP of 6 mmHg or greater and of 21 mmHg or less in two or more consecutive follow-up visits without further glaucoma surgery or loss of light perception attributable to glaucoma. RESULTS: The overall success rates were 87% for the 350-mm2 group and 70% for the 500-mm2 group (P = 0.05). Average follow-up was 37 months (range, 1-76 months) for the 350-mm2 group and 34 months (range, 5-77 months) for the 500-mm2 group. The life-table success rates declined over time for both implant groups, from a high of 98% for the 350-mm2 group and 92% for the 500-mm2 group at 1 year to a cumulative success rate of 79% for the 350-mm2 group and 66% for the 500-mm2 group at 5 years. Visual acuities were better or remained the same in 50% of the patients in the 350-mm2 group and 46% of those in the 500-mm2 group. Complications during the 5-year follow-up were also statistically similar. CONCLUSIONS: The longer term results show that the 350-mm2 Baerveldt implant is more successful than the 500-mm2 implant for overall IOP control. Interval comparisons indicate a higher rate of success for the 350-mm2 implant in the first, second, third, fourth, and fifth years of implantation. Visual acuities, implant-related complications, and average IOPs were statistically indistinguishable between the two groups.     

Long-term use of diazepam

Plasma concentrations of diazepam and its major active metabolite nordiazepam were measured in 108 neurosurgical patients taking diazepam in doses of 5 to 40 mg/day for periods from one month to 16 years. Diazepam was used for relief of pain or muscle spasm, or anxiety and sleeplessness associated with these two symptoms, and was considered to be beneficial by 83% of the patients, although use of other drugs confounded this evaluation. Concentrations of total diazepam-nordiazepam ranged from 0 to 2,584 ng/mL, with nordiazepam being the predominant metabolite. "Low" concentrations (less than 250 ng/mL) were found in 35 of the 108 patients, with 19 having concentrations lower than 100 ng/mL. "High" concentrations (greater than 900 ng/mL) were found in 20 patients and did not occur more frequently than in other studies of long-term diazepam ingestion. Even with long-term use, diazepam seemed to retain its efficacy and did not lead to any clear-cut abuse.     

Intracellular uptake and cytotoxic effect in vitro of doxorubicin and epirubicin in human leukemic and normal hematopoietic cells

Summary Leukemic cells from patients presenting with acute nonlymphoblastic leukemia and normal hematopoietic bone marrow cells from healthy donors for allogeneic bone marrow transplantation were incubated for 3 h with doxorubicin and epirubicin at different concentrations. The intracellular uptake at the end of the incubation was determined by photofluorometry in leukemic cells from 15 patients and in normal cells from 9 donors for bone marrow transplantation. Cytotoxicity in vitro against granulocyte/macrophage colony-forming units (CFU-GM) was determined in normal cells from 7 donors, and in vitro toxicity against leukemic cells was determined by a clonogenic technique in cells from 6 patients and by vital dye staining (DiSC) following 4 days' culture in cells from 15 patients. Epirubicin was significantly less toxic than doxorubicin to normal hematopoetic cells (72%±20% survival of cells for epirubicin vs 45%±13% for doxorubicin at a concentration of 0.2 m;P0.005). As analyzed by the DiSC assay, 0.2 m epirubicin was slightly more toxic to leukemic cells than was the same concentration of doxorubicin (47% vs 61% survival,P0.01), but the clonogenic assay revealed no difference in toxicity to leukemic cells. At a concentration of 0.2 m, the mean intracellular uptake of epirubicin in leukemic cells was 0.43±0.26 nmol/mg protein as compared with 0.33±0.14 nmol/mg protein for doxorubicin (not significant). In normal cells, the uptake of epirubicin at a concentration of 0.2 m was 0.47±0.25 nmol/mg protein as compared with 0.31±0.21 nmol/mg protein for doxorubicin (not significant). The reduced myelotoxicity observed in vitro together with the retained toxicity to leukemic cells indicates that the therapeutic index of epirubicin is better than that of doxorubicin.     

Implanon: user views in the first year across three family planning services in the Trent Region, UK.

OBJECTIVE: Implanon (NV Organon, Oss, The Netherlands) was released in the United Kingdom towards the end of 1999. This survey elicited the experiences of women who had the new implant inserted in three family planning services in North Trent, UK during the first year after its introduction. METHOD: A previously piloted questionnaire was sent to all Implanon users who had the devices fitted in the three services between December 1999 and December 2000. Returned questionnaires were analyzed. RESULTS: Health-care providers and friends or family were the main sources of information about the single-rod contraceptive implant for the survey population. Women considered themselves informed about the method prior to insertion irrespective of whether they continued to use the method or requested early removal. Ease of use was the most common reason for choosing Implanon and one of the best-liked features. Bleeding irregularities were the most commonly reported side-effect, followed by weight gain, moods and headaches. Bleeding problems led to the majority of removal requests; the wish for pregnancy was not stated at all. The single-rod implant compared favorably with most responders' experiences with other methods of contraception. Further research into motivation and perceptions regarding modern contraceptives may be required in different populations.     

Neugeborenenhörscreening mit dem automatisierten Meßgerät Echosensor für otoakustische Emissionen Eine vergleichende Untersuchung

Zusammenfassung Die Messung otoakustischer Emissionen (OAE) wird für H?rscreeninguntersuchungen von Neugeborenen auf Empfehlung der NIH Consensus Conference im Jahre 1993 in den USA und Europa eingesetzt. Obwohl diese Messungen gegenüber anderen objektiven Me?verfahren einfacher durchzuführen sind, erfordert die Bedienung des Systems und die Interpretation der Ergebnisse speziell geschultes Personal. Ein allgemeines objektives H?rscreening in Deutschland hat sich bisher weder bei Neugeborenen noch bei Risikokindern durchgesetzt, obwohl es wünschenswert w?re, Kinder mit angeborener Innenohrschwerh?rigkeit (Inzidenz: 1–6 von 1000) m?glichst früh zu erfassen, zu therapieren und zu rehabilitieren. Der Echosensor bietet die M?glichkeit, TEOAE-Messungen mit kurzer Me?zeit durchzuführen und automatisiert zu bewerten. Sie k?nnten auch von angelerntem Personal durchgeführt werden. Um die Ergebnisse des Echosensors mit denen des konventionellen TEOAE-Me?ger?ts ILO88 zu vergleichen, wurden OAE-Messungen an 111 Neugeborenen von audiologisch geschulten Personen durchgeführt. Im Rahmen dieser Pilotstudie wurden Reliabilit?t und Validit?t der Messungen im Vergleich zum Goldstandard der Hirnstammaudiometrie bestimmt. Es zeigte sich eine sehr hohe übereinstimmung (Sensitivit?t 100%, Spezifit?t 93,3%) zwischen den Ergebnissen beider Methoden. Somit steht mit dem Echosensor ein OAE-Me?verfahren zur Verfügung, das eine hohe Sensitivit?t und Spezifit?t aufweist und zu einfach bedienen ist. Dieses Ger?t k?nnte einem fl?chendeckenden Einsatz des H?rscreenings in Deutschland den Weg ebnen. Eingegangen am 22. Dezember 1996 Angenommen am 9. Juli 1998     

Rectus muscle orbital wall fixation: a reversible profound weakening procedure.

INTRODUCTION: Surgical treatment of third nerve palsy, sensory exotropia and strabismus secondary to anomalous innervation of the rectus muscles, frequently require large rectus muscle recessions in an attempt to maintain alignment in the primary position and reduce the effects of misinnervation. The aim of this study was to describe and evaluate the results of inactivation of a rectus muscle by its attachment to the adjacent orbital wall. METHODS: Seven subjects diagnosed with third-nerve palsy (three cases), Duane syndrome (two cases), sensory exotropia (one case), and congenital aberrant innervation of vertical rectus muscles (one case) underwent rectus muscle inactivation by orbital wall fixation. The rectus muscle was disinserted from the globe and reattached to the adjacent orbital periosteum using non-absorbable sutures. This surgery was performed on the lateral rectus muscle in six subjects, and surgery was performed on both ipsilateral vertical rectus muscles in one. RESULTS: Postoperatively four of six patients were aligned within 12 prism diopters of orthotropia in primary position. All patients had improvement of the anomalous head posture. In Duane syndrome, lateral rectus inactivation markedly reduced co-contraction and globe retraction. No overcorrections resulted. CONCLUSION: A rectus muscle may be functionally inactivated when its insertion is attached to the orbital periosteum. Advantages of this procedure over extirpation and free tenotomy include permanent disinsertion of the muscle from globe and reversibility.