Velocardiofacial syndrome: are structural changes in the temporal and mesial temporal regions related to schizophrenia?

OBJECTIVE: Velocardiofacial syndrome results from a microdeletion on chromosome 22 (22q11.2). Clinical studies indicate that more than 30% of children with the syndrome will develop schizophrenia. The authors sought to determine whether neuroanatomical features in velocardiofacial syndrome are similar to those reported in the literature on schizophrenia by measuring the volumes of the temporal lobe, superior temporal gyrus, and mesial temporal structures in children and adolescents with velocardiofacial syndrome. METHOD: Twenty-three children and adolescents with velocardiofacial syndrome and 23 comparison subjects, individually matched for age and gender, received brain magnetic resonance imaging (MRI) scans. Analysis of covariance models were used to compare regional brain volumes. Correlations between residualized brain volumes and age were standardized and compared with the Fisher r-to-z transformation. RESULTS: Children with velocardiofacial syndrome had significantly smaller average temporal lobe, superior temporal gyrus, and hippocampal volumes than normal comparison children, although these differences were commensurate with a lower overall brain size in the affected children. In a cross-sectional analysis, children with velocardiofacial syndrome exhibited aberrant volumetric reductions with age that were localized to the temporal lobe and left hippocampal regions. CONCLUSIONS: Abnormal temporal lobe and hippocampal development in velocardiofacial syndrome is potentially concordant with MRI findings in the schizophrenia literature. Temporal lobe and mesial temporal structures may represent a shared substrate for the effects of the 22q11.2 deletion and for the complex etiological pathways that lead to schizophrenia. Longitudinal research may help determine which children with velocardiofacial syndrome are at risk for serious psychiatric illness in adulthood.

Control and management of ovarian follicles in cattle to optimize fertility.

Experiments were designed to elucidate the control of ovarian follicle turnover and the impact of follicular dynamics on the subsequent fertility of dairy cattle. An experimental model was established to examine the interrelationships of gene expression for steroid enzymes, the insulin-like growth factor system and inhibin production as associated with follicle selection, dominance and atresia. Follicular dynamics during the postpartum period and the oestrous cycle are shown to be altered markedly by the metabolic demands of lactation. The feeding of ruminally-inert fat stimulated follicular development and improved reproductive performance. The development of persistent follicles during oestrus synchronization causes a reduction in fertility that can be corrected by recruitment and selection of a new ovulatory follicle after the injection of a gonadotrophin-releasing hormone agonist. Present systems of oestrus synchronization need to consider both synchronization of follicular development and corpus luteal regression in order to optimize fertility. With current systems manipulating follicle development, the potential to implement a timed insemination programme to improve reproductive management exists. Ovulation of the first-wave dominant follicle with human chorionic gonadotrophin provides a means to markedly enhance concentrations of plasma progesterone in the luteal phase.

The dominant follicle exerts an interovarian inhibition on FSH-induced follicular development.

An experiment was conducted to evaluate the role of the dominant follicle (DF) of the first wave in regulating follicular and ovulatory responses and embryonic yield to a superovulation regime with FSH-P. Twenty normally cycling Holstein-Freisian heifers (n = 20) were synchronized with GnRH and pgf(2alpha) and randomly assigned to a control or a treated group (n = 10 each). Treated heifers had the first wave dominant follicle removed via transvaginal, ultrasound-guided aspiration on Day 6 after a synchronized estrus. All heifers received a total of 32 mg FSH-P given in decreasing doses at 12 h intervals from Day 8 to Day 11 plus two injections of pgf(2alpha) (35 mg and 20 mg, respectively) on Day 10. Heifers were inseminated at 6 h and 16 h after onset of estrus. Follicular dynamics were examined daily by transrectal ultrasonography from Day 4 to estrus, once following ovulation, and at the time of embryo collection on Day 7. Blood samples were collected daily during the superovulatory treatment and at embryo collection. Follicles were classified as: small, /= 10 mm. Aspiration of the dominant follicle was associated with an immediate decrease in large follicles, and a linear rate increase in small follicles from Day 4 to Day 8 just prior to the FSH-P injections, (treatment > control: +0.33 vs. -0.22, number of small follicles per day; P < 0.10). During FSH-P injections, the increase in number of medium follicles was greater (P < 0.01) for treatment on Day 9-11 (treatment > control: Day 9, 3.2 > 1.8; Day 10, 9.2 > 4.7; Day 11, 13.1 > 8.3; +/- 0.56). Number of large follicles was greater in treatment at Day 11 (5.12 > 1.4 +/-0.21; P < 0.01). Mean number of induced ovulatory follicles (difference between number of follicles at estrus and Day 2 after estrus) was greater in treatment (13.4 > 6.3 +/- 1.82; P < 0.01). Plasma estradiol at Day 11 during FSH-P treatment was greater in treatment (32.5 > 15.8 +/- 2.6; P < 0.01). Plasma progesterone at embryo flushing (Day 7 after ovulation) was greater in treatment (7.4 > 4.9; P < 0.02); technical difficulties at embryo recovery reduced sensitivity of embryonic measurements. No changes in the distribution of unfertilized oocytes and embryo developmental stages were detected between control and treatment groups. Presence of dominant follicle of the first wave inhibited intraovarian follicular responses to exogenous FSH.

Effects of buserelin injection and deslorelin (GnRH-agonist) implants on plasma progesterone, LH, accessory CL formation, follicle and corpus luteum dynamics in Holstein cows.

The influence of Buserelin injection and Deslorelin (a GnRH analogue) implants administered on Day 5 of the estrous cycle on plasma concentrations of LH and progesterone (P4), accessory CL formation, and follicle and CL dynamics was examined in nonlactating Holstein cows. On Day 5 (Day 1 = ovulation) following a synchronized estrus, 24 cows were assigned randomly (n = 4 per group) to receive 2 mL saline, i.m. (control), 8 micrograms, i.m. Buserelin or a subcutaneous Deslorelin (DES) implant in concentrations of 75 micrograms, 150 micrograms, 700 micrograms or 2100 micrograms. Blood samples were collected (for LH assay) at 30-min intervals for 2 h before and 12 h after GnRH-treatment from cows assigned to Buserelin, DES-700 micrograms and DES-2100 micrograms treatments and thereafter at 4-h intervals for 48 h. Beginning 24 h after treatment, ovaries were examined by ultrasound at 2-h intervals until ovulation was confirmed. Thereafter, ultrasonography and blood sampling (for P4 assay) was performed daily until a spontaneous ovulation before Day 45. A greater release of LH occurred in response to Deslorelin implants than to Buserelin injection (P < 0.01). Basal levels of LH between 12 and 48 h were higher in DES-700 micrograms group than in DES-2100 micrograms and Buserelin (P < 0.05). The first wave dominant follicle ovulated in all cows following GnRH treatment. Days to CL regression did not differ between treatments, but return to estrus was delayed (44.2 vs 27.2 d; P < 0.01) in cows of DES-2100 micrograms group. All GnRH treatments elevated plasma P4 concentrations, and the highest P4 responses were observed in the DES-700 micrograms and DES-2100 micrograms groups. The second follicular wave emerged earlier in GnRH-treated than in control cows (9.9 vs 12.8 d; P < 0.01). However, emergence of the third dominant follicle was delayed in cows of DES-2100 micrograms treatment (37.0 d) compared with DES-700 micrograms (22.2 d), Buserelin (17.8 d) or control (19.0 d). In conclusion, Deslorelin implants of 700 micrograms increased plasma P4 and LH concentrations and slightly delayed the emergence of the third dominant follicle. On the contrary, Deslorelin implants of 2100 micrograms drastically altered the P4 profiles and follicle dynamics.

Use of a gonadotropin-releasing hormone agonist or human chorionic gonadotropin for timed insemination in cattle.

Three experiments were conducted to evaluate a synchronization protocol with AI at a predetermined time. In Exp. 1, 169 dairy heifers were assigned randomly to two groups: 1) timed AI (TAI), consisting of GnRH agonist injection (d 0, 1700), PGF2 alpha injection (d 7, 1700), GnRH agonist injection (d 8, 1700), and AI (d 9, 0800); and 2) AI at estrus (AIE), consisting of GnRH agonist injection (d 0, 1700), PGF2 alpha injection (d 7, 1700), and AI at detected estrus. Pregnancy rate was 25.8% for TAI (n = 89) compared with 48.7% for AIE (n = 80; P < .001). Experiment 2 was comparable to Exp. 1, but the second GnRH agonist injection in TAI was given 48 h after injection of PGF2 alpha. Heifers in TAI (n = 187) were inseminated at detected estrus if estrus occurred within 39 h after administration of PGF2 alpha (n = 47). Pregnancy rates were 45.5% for TAI and 48.0% for AIE (n = 177). Conception rate was reduced for TAI (45.5 [85/187] < 61.2% [85/139]; P < .005). In Exp. 3, the second injection of GnRH agonist, given at 48 h after injection of PGF2 alpha, was replaced with hCG (3,000 IU, i.m.). No differences in pregnancy rate were detected for TAI (52.9% [54/102]) vs AIE (56.1% [55/98]). Conception rate was reduced for TAI (52.9 [54/102] < 72.3% [55/76]; P < .005). Delaying the second GnRH agonist injection by 24 h improved pregnancy rate, but replacing the second injection of GnRH agonist with an injection of hCG did not prevent a reduction in conception rate.

Human chorionic gonadotropin-induced alterations in ovarian follicular dynamics during the estrous cycle of heifers.

This experiment was designed to characterize hCG (3,000 IU)-induced alterations in ovarian follicular and corpus luteum (CL) dynamics during the estrous cycle (EC) in heifers. Following synchronization of estrus (norgestomet implant for 7 d with injection of PGF2alpha 1 d before implant removal), 13 heifers were treated with either hCG (n = 6) or saline (control group; n = 7) on d 5 of the EC (d 0 = day of estrus). Blood sampling from the jugular vein and ultrasonography of both ovaries were conducted daily until confirmation of ovulation following a detected estrus. Treatment with hCG at d 5 induced formation of an accessory CL in all hCG-treated heifers. Subsequent plasma progesterone (P4) concentrations were higher (P < .01) between d 9 and 17 for the hCG group than for the control group. More (P < .05) hCG-treated heifers had EC with three waves of follicles than control heifers. The second-wave dominant follicle (DF) emerged earlier in hCG than in control heifers (7.3 vs 10.4 d; P < .01). A group x wave interaction (P < .01) was detected for duration of the second and third wave follicles; hCG treatment decreased duration of the second wave (6.3 vs 9.3 d) and increased duration of the third wave (9.2 vs 5.3 d). The hCG-treated heifers had preovulatory follicles that lasted longer (P < .01) on the ovary than those in control heifers. However, plasma estradiol concentrations did not differ (P > .10) between hCG-treated and control heifers during the preovulatory period. A wave x duration interaction (P < .01) was detected for P4 concentrations, between d 13 and 22, for heifers with two vs three spontaneous-wave EC. Higher P4 concentrations during the luteal phase may contribute to a greater rate of follicular turnover or frequency of three-wave cycles, and lower P4 concentrations were associated with two-wave cycles.

Effect of a gonadotropin-releasing hormone agonist on follicle recruitment and pregnancy rate in cattle.

Two experiments were conducted to determine whether a GnRH agonist eliminated a potentially persistent first-wave dominant follicle (PDF) and recruited a new dominant follicle with improved fertility upon ovulation. In Exp. 1, five nonlactating Holstein cows were treated on d 7 (d 0 = estrus) with a norgestomet implant and PGF2 alpha (25 mg); a GnRH agonist was injected on d 9. On d 16, the norgestomet implant was removed and PGF2 alpha was injected. The corpus luteum (CL) regressed (5/5 cows), and plasma progesterone (P4) decreased (P < .01) from d 7 (P4 = 10.4 +/- .3) to 9 (P4 = 1.0 +/- .3 ng/mL). The GnRH agonist induced ovulation of the first-wave dominant follicle. New dominant follicles emerged by d 12 +/- 1. In all cows, removal of norgestomet implants and injection of PGF2 alpha on d 16 caused regression (P < .01) of the CL induced by the GnRH agonist. The GnRH agonist-recruited dominant follicles were highly estrogenic on d 17 (estradiol = 19.6 +/- .8 pg/mL) and ovulated on d 19.8 +/- .2 (5/5). In Exp. 2, 147 heifers at a synchronized estrus were assigned disproportionally but randomly to two treatments (GnRHa, n = 94; PDF, n = 53). On d 7, a used controlled internal drug releasing (CIDR-B) device was inserted into the vagina and PGF2 alpha was injected. On d 9, heifers in GnRHa were injected with GnRH agonist. The CIDR-B devices were removed and PGF2 alpha was injected into all heifers on d 16. Within 4 d after removal of CIDR-B devices, 96.8 and 94.3% of heifers in GnRHa and PDF were detected in estrus and inseminated. Pregnancy rates were GnRHa = 60.6% > PDF = 43.4% (P < .05). In summary, fertility after ovulation of a persistent first-wave dominant follicle is reduced, whereas induction of a new dominant follicle following injection of a GnRH agonist results in greater fertility.

A cellular and endocrine characterization of the original and induced corpus luteum after administration of a gonadotropin-releasing hormone agonist or human chorionic gonadotropin on day five of the estrous cycle.

To determine whether injection of hCG or GnRH-agonist on d 5 after estrus (d 0) has a differential functional effect on an induced and the original corpus luteum (CL), two experiments were conducted. In Exp. 1, nonlactating Holstein cows were injected on d 5 with saline (n = 4; T1), a GnRH-agonist (Buserelin, 8 micrograms i.m.; n = 4; T2), or hCG (1,000 i.u., i.v., and 2,000 i.u., i.m.; n = 4; T3). Induced CL were removed on d 13 and weights were different (GnRH-agonist < hCG). In vitro production of progesterone by CL tissue (microgram/g; microgram/CL) was affected by treatment (GnRH-agonist < hCG) and dose of LH (ng.mL) in culture media. Experiment 2 was a replicate of Exp. 1, except that the original CL was removed on d 17 for in vitro culture. Day-17 CL weights and in vitro production of progesterone by original CL were not affected by treatment. The daily rate of increase of plasma progesterone from d 6 to d 13 differed: saline < GnRH-agonist < hCG (P < .01). From d 14 to 17, the rate of plasma progesterone decrease was not different between treatments. Electron micrographic study of the original and induced CL indicates that LH-like exposure delays involution of steroidogenic luteal cells. In summary, the higher levels of progesterone from d 6 to d 13 of the estrous cycle following an injection of hCG vs GnRH-agonist on d 5 is due to a greater response of hCG-induced CL.

Differential response of the luteal phase and fertility in cattle following ovulation of the first-wave follicle with human chorionic gonadotropin or an agonist of gonadotropin-releasing hormone.

A series of experiments with Holstein heifers was conducted to develop the capability of inducing accessory corpus luteum (CL) with a GnRH agonist (Buserelin, 8 micrograms; GnRHa) or hCG (3,000 IU) to increase plasma progesterone concentrations (Exp. 1, 2, and 3) and to test whether induction of accessory CL with hCG will increase conception rates in heifers (Exp. 4) and lactating cows (Exp. 5). In Exp. 1, heifers were treated on d 5 after estrus with GnRHa (n = 8) or saline (n = 7); heifers in Exp. 2 received hCG (n = 5) or saline (n = 4) on d 5. Experiment 3 allowed a contemporary evaluation of heifers treated on d 5 with GnRHa (n = 6), hCG (n = 6), saline (n = 6), or GnRHa at d 5 and hCG at the time of the induced ovulation (n = 5). The GnRHa and hCG were equally effective in inducing an accessory CL (93% induction rate), but the subsequent increase in progesterone concentrations was greater in hCG-treated heifers. A greater half life of hCG may provide longer LH-like stimulation of the first-wave follicle and subsequent developing accessory CL or a greater luteotropic effect on the original CL. Induction of an accessory CL with hCG on d 5 or 6 after insemination did not increase pregnancy rates in fertile heifers (Exp. 4: hCG = 64.8% vs control = 62.9%; n = 243) or lactating dairy cows during summer heat stress (Exp. 5: hCG = 24.2% vs control = 23.5%; n = 201).

[A simplified drainage/irrigation system for extracapsular cataract extraction]. / Ein vereinfachtes Saug-Spülsystem zur extrakapsulären Kataraktextraktion.

A simplified irrigation/aspiration system has been developed by the author in cooperation with the Klein company of Heidelberg. The suction is produced by connecting the instrument to a commonly used aspirator. The aspiration force is regulated by means of a foot-pedal, which regulates the amount of "bypass air" delivered through a special tube connected to the irrigation/aspiration handpiece. This simple i/a system represents a low-priced alternative to other systems already on the market.

[Diagnostics of intraocular tumors with the radiophosphorus test (author's transl)]. / Zur Diagnostik intraokularer Tumoren mit dem 32P-Test.

The author reports about the radio-phosphorus-test as an additional method in diagnostics of intraocular tumors in 62 examinations. The conformity between 49 histologically examined cases and the positive test-results amounted to 90%.

[Eye injuries caused by traffic accidents]. / Augenverletzungen durch Verkehrsunfälle.

Severe injuries of the eyes and the periocular region may happen to those people, not secured by a safety belt, while the head crashes against the windshield in case of a car accident. These injuries typically run across the nose, the front and the eyelids, while other parts of the face are often not involved. Besides these wounds, the eyes show corneal and scleral perforations, loss of lens and iris as demonstrated by some victims of traffic accidents. Studies have shown that the most serious head- and eye-injuries occur to people in a frontal collision, which is the most common type of collision. On the other hand, the risk to be injured at the head or the eyes in a frontal collision while using the safety belt is under 1%.

[New forceps for the implantation of posterior chamber lenses]. / Eine neue Pinzette zur Hinterkammerlinsenimplantation.

Forceps used for implanting posterior chamber lenses of the Shearing or Sinskey/Kratz type have the disadvantage that they do not permit the lens to be safely guided during implantation. This advantage is avoided by a special pair of forceps (made by Klein ophthalmological instruments of Heidelberg, Germany). The branches of the forceps are designed in such a way that the angle between them and the lens is constantly 130 degrees, thus insuring an unobstructed view into the eye while inserting the lens. Moreover, the lens cannot shift laterally around the branch inserted into the hole. Slight opening of the branch causes the lens to slide off the forceps. With these new implantation forceps the lens can thus be inserted into the eye safely and in a predetermined position during the first stage of implantation.

[Ophthalmological symptoms following extrathoracal reanimation (author's transl)]. / Ophthalmologische Befunde nach extrathorakaler Reanimation.

In patients with cardiac arrest and extrathorakal reanimation, hyposphagma, vitreous and retinal hemorrhages, fat embolism in the retinal arteries as well as fluffy exudates of the fundus were observed. Pathogenesis and connections with Purtscher's traumatic angiopathic retinopathy are discussed.

[The development of eye symptoms in dysostosis craniofacialis Crouzon--a contribution to pathogenesis (author's transl)]. / Die Entstehung der Augenbefunde bei Dysostosis craniofacialis Crouzon--ein Beitrag zur Pathogenese.

The eye symptoms in dysostosis craniofacialis Crouzon can be divided into obligate and facultative signs; the latter are nystagmus, megalocornea, coloboma of the iris, corectopia, ectopia of the lens and cataract. There is no causal relationship between these symptoms and the dysostosis craniofacialis. The common eye findings in this disease use proptosis, divergent strabism, hypertelorism with dystopia canthi lateralis as well as in about 80% an atrophy of the optic nerve. It is considered until now that the premature synostosis of cranial sutures is the leading and only pathogenetical factor in this disease. This theory can no longer be sustained because of its inability to explain the above mentionned eye findings. We want to stress on a malformation of the prosencephalic head organisator leading to a dyschondroplasia that mainly affects the base of the skull. This frontal dysplasia causes a characteristic displacement of the building materials and thereby produces the common eye findings in this disease.

[A modified cataract incision: limbal step incision with partial conjunctival covering of the suture (author's transl)]. / Ein modifizierter Starschnitt: limbärer Stufenschnitt mit partieller Bindehautdeckung der Naht.

The authors describe a cataract incision technique, which combines the advantages of the corneoscleral site (conjunctival covering, mechanical strength of the resulting scar) with those of a corneal incision (sparing of the angle structures, good visibility, simple and nontraumatic suture removal) and those of a continuous nylon suture (unimpaired wound healing, even adaptation).

[Visual perception under the influence of a tranquilizer (author's transl)]. / Die visuelle Wahrnehmung unter Einfluss eines "Arbeitstranquilizers" (Albego).

In a double blind study, the influence of the tranquilizer Camazepam on different ophthalmological parameters was examined. The 12 test persons were between 20 and 30 years of age and had entirely normal ocular findings. Visual acuity was uninfluenced by a single dose of 40 mg of Camazepam, reflecting the very slightly hypnotic effect of the drug. Roughly half of the patients showed a considerable widening of the visual field, thought to be related to the stimulation of attention caused by Camazepam. Finally the lack of muscle relaxing properties of Camazepam was confirmed as regards the extraocular muscles, since their balance remained uninfluenced as well.

Pharmacokinetics of ceftiofur in plasma and uterine secretions and tissues after subcutaneous postpartum administration in lactating dairy cows.

A study was conducted to measure concentrations of potentially active ceftiofur derivatives, in plasma, in uterine tissues (endometrium and caruncles) and in uterine secretions at different time points after a single subcutaneous administration of ceftiofur hydrochloride (Excenel RTU Sterile Suspension) at the dose of 1 mg/kg body weight in Holstein-Friesian dairy cows. The animals (n=4) were injected within 24 h of calving, after expulsion of the foetal membranes. Plasma, lochial fluid, caruncles and endometrium were collected before ceftiofur hydrochloride administration and at 1, 2, 4, 8, 12 and 24 h after treatment. For each cow the concentrations of ceftiofur in the biological matrices were quantified using an high-performance liquid chromatography (HPLC) assay. The limit of quantification of the method was 0.1 microg/mL for plasma and 0.1 microg/g for lochial fluid, caruncles and endometrium. The concentrations of potentially active ceftiofur derivatives detected in plasma reached a maximum of 2.85 +/- 1.11 microg/mL at 2 h and decreased to 0.64 +/- 0.14 microg/mL at 24 h after administration. In lochial fluid, these concentrations reached a maximum of 0.97 +/- 0.25 microg/g at 4 h and decreased to 0.22 +/- 0.21 microg/g at 24 h after administration. In endometrium, these concentrations reached a maximum of 2.23 +/- 0.82 microg/g at 4 h and decreased to 0.56 +/- 0.14 microg/g at 24 h following the injection, whereas these levels in caruncles were 0.96 +/- 0.45 and 0.60 +/- 0.39 microg/g obtained at 8 and 24 h, respectively. At the dose of 1 mg/kg body weight in healthy dairy cows, subcutaneous administration of ceftiofur (as ceftiofur hydrochloride) after parturition results in concentrations of ceftiofur derivatives in uterine tissues and in lochial fluid that exceed the reported minimal inhibitory concentrations (MICs) for the common pathogens (Escherichia coli, Fusobacterium necrophorum, Bacteroides spp., and Arcanobacterium pyogenes) associated with acute puerperal metritis.