Potency following conformal neutron/photon irradiation for localized prostate cancer

: To assess the effect of conformal neutron/photon irradiation with or without neoadjuvant hormonal therapy on posttreatment potency.

: Seventy-six patients with localized adenocarcinoma of the prostate, Stage T1 or T2 N0 Mo, Gleason score ≤7, were enrolled on a prospective Phase II study. Each patient received 9–10 Neutron + 38 Photon Gy. Twenty-eight patients received neoadjuvant hormonal therapy in conjunction with radiation therapy. Potency was assessed prior to starting treatment and was assessed at each subsequent follow-up visit.

: Fifty-two of 75 patients (70%) were potent at the start of therapy. Thirty-eight of 52 (73%) had functional erections and 14 of 52 (27%) had erections termed nonfunctional, which were of insufficient strength for intercourse. After treatment, 35 of 52 (67%) retained potency. Twenty-nine of 38 (76%) with functional erections pretreatment maintained this ability. Only 6 of 14 patients (43%) with nonfunctional erection pretreatment maintained their level of potency. Neoadjuvant hormonal therapy did not impact on the ability to maintain erections. Sixty-five percent of those patients receiving hormones retained erectile function, while 69% of those who did not receive hormones maintained erectile function. Age was not a significant factor in posttreatment potency, although a trend towards potency in younger patients was observed . (p = 0.74).

: The majority (67%) of patients maintained their level of erectile function following conformal sequential neutron photon irradiation. This comparable to that achieved with photon irradiation alone. No significant change in potency was seen with neoadjuvant hormonal therapy or with increasing patient age.     

Radiation survival of two human cervical carcinoma cell lines after multifraction irradiation

: Multifraction irradiation may contribute to radiation therapy treatment failure is selection of radiation resistant subpopulations occurs. We sought to determined whether surviving cells following daily fraction irradiation of two human cervical squamous cell carcinoma lines would express different radiation survival characteristics compared to the unirradiated parent.

: A late-passage line (HTB35) and an early-passage line 9RECA) received daily 2 Gy x-irradiation. Two stable HTB35 cell lines were extablished after 40 and 60 Gy (HTB3540 and HTB3560). A single line was established from RECA after 30 Gy (RECA-30). High dose rate (74 cGy/min) acute radiation survival curves were prepared from the three nre lines and the unirradiated parents. Potentially lethal damage repair (PLDR) and sublethal damage repair (SLDR) responses were detailed for HTB35, HTB3540 and HTB3560. Low dose rate (1.27 cGy/min) survival was measured dfor HTB35 and HTB3560. Clones were derived from HTB35 and from HTB3560 and the survivung fraction at 2 Gy (SF₂) values were determined.

: The two parent lines (HTB35 and RECA) differed in acute radiation survival. The surviving lines following multifraction irradiation (HTB3540, HTB3560, and RECA) showed no change in acute radiation response compared to the appropriate parent. HTB3540 and HTB3560 were repair proficient, demonstrating similar PLDR anmd SLDR recovery ratios as the parent. Likewise, low dose rate survival of HTB35 and HTB3560 was similar. Nine clones derived deom HTB35 lacked a consistent difference in SF₂ compared to the original culture. A single clone of seven derived from HTB3560 was consistently radiation resistant (SF₂ = 0.81 ± 0.06 compared to the original culture (SF₂ = 0.50 ± 0.09).

: No evidence was obtained that cell lines generated following multiple daily fractions of x-irradiation in vitro possessed acute radiation survival or repair characteristics that were different from the unirradiated parent.     

A Longitudinal Study on Growth and Spontaneous Growth Hormone (GH) Secretion in Children with Irradiated Brain Tumors

ABSTRACT. Longitudinal growth was studied in 27 children after radiotherapy for a brain tumor. Growth deviation (1 SD) was found in 56% of the children after 2 years and was most profound in prepubertal children aged between 3 and 8 years at the time of irradiation. In this group growth velocity was markedly reduced and no catch up was seen. In all children studied growth hormone (GH) secretion, measured as the spontaneous secretion over 24 hours, was found to be severely disturbed. Our conclusion is that all children with a growth deviation 1 SD after radiotherapy (40 Gy) to the hypothalamo–hypophyseal region should be considered GH deficient. In such children GH treatment can be initiated without further testing.     

Long-term changes in postnatal susceptibility to pilocarpine-induced seizures in rats exposed to gamma radiation at different stages of prenatal development

PURPOSE: To determine whether brains irradiated at different stages of prenatal development also have different postnatal susceptibility to seizures evoked by pilocarpine. METHODS: Pregnant Wistar rats were exposed to a single 1.0-Gy dose of gamma rays on gestation days 13, 15, 17, or 19 (E13, E15, E17, and E19, respectively). On postnatal day 60, their offspring received i.p. pilocarpine injections to evoke status epilepticus. Behavior of the animals was observed continuously for 6 h after the injection, and motor manifestations of seizure activity were rated, and survival times recorded. After 7-day survival, the animals were killed, and their brains were weighed. RESULTS: The average brain weight of animals exposed to irradiation at earlier prenatal stages (E13 or E15) was significantly lower than that after irradiation on E17 or E19. However, effects of the irradiation on the susceptibility to pilocarpine-induced seizures were quite opposite. The intensity of status epilepticus evoked in rats irradiated on E13 or E15 was significantly lower than that in nonirradiated controls or in those irradiated on E17 or E19. Moreover, after irradiation on E13 or E15, survival of the animals was significantly higher in relation not only to other irradiated groups but also to the controls. CONCLUSIONS: The results suggest than the extent of neuronal deficit, even if relatively greater, cannot always lead to higher susceptibility of the dysplastic brain to seizures. Functional consequences of the deficit, even if its magnitude is relatively smaller but involving specific brain areas, appear to be critical for the epileptogenesis.     

G protein subunit G gamma 13 is coexpressed with G alpha o,G beta 3, and G beta 4 in retinal ON bipolar cells

We investigated the expression of Ggamma13, a recently discovered G protein subunit, and a selection of Gbeta subunits in retinal bipolar cells, by using a transgenic mouse strain in which green fluorescent protein is strongly expressed in a single type of cone bipolar cell. The cells have ON morphology, and patch-clamp recordings in slices confirmed that they are of the physiological ON type. Immunohistochemistry showed that Ggamma13 is expressed in rod bipolar cells and ON cone bipolar cells, where it is colocalized in the dendrites with Galphaomicron. ON and OFF cone bipolar cells and rod bipolar cells were identified among dissociated cells by their green fluorescence and/or distinct morphology. Hybridization of single-cell polymerase chain reaction products with cDNA probes for G protein subunits Gbeta1 to 5 showed that Gbeta3, Gbeta4, and Ggamma13 are coexpressed in ON bipolar cells but not present in OFF bipolar cells. Gbeta1, 2, and 5 are expressed in partially overlapping subpopulations of cone bipolar cells. Ggamma13 and Gbeta3 and/or Gbeta4, thus, seem selectively to participate in signal transduction by ON bipolar cells.     

Inactivation of viral and prion pathogens by gamma-irradiation under conditions that maintain the integrity of human albumin

BACKGROUND AND OBJECTIVES: The administration of therapeutic plasma protein concentrates has been associated with the real risk of transmitting viral diseases and the theoretical risks of prion transmission. Our objective was to determine if gamma-irradiation can inactivate viral or prion infectivity without damaging a protein biotherapeutically. MATERIALS AND METHODS: Human albumin 25% solution, spiked with four model viruses (including porcine parvovirus) or with brain homogenate from scrapie-infected hamsters, was gamma-irradiated at constant low-dose rates and assayed for viral and prion infectivity or for albumin integrity. RESULTS: At a radiation dose of 50 kGy, viruses were inactivated by >/= 3.2 to >/= 6.4 log10 and scrapie by an estimated 1.5 log10, whereas albumin was only moderately aggregated and fragmented. CONCLUSIONS: gamma-Irradiation can preferentially inactivate viral and prion pathogens without excessive damage to albumin structure.     

Characteristics of patients with abnormal stress technetium Tc 99m sestamibi SPECT studies without significant coronary artery diameter stenoses

BACKGROUND: Single-photon emission computed tomography (SPECT) sestamibi (MIBI) is an excellent tool for detection of coronary artery disease (CAD), preoperative risk assessment, and follow-up management after coronary revascularization. While the sensitivity of MIBI SPECT for detecting CAD has been reported to exceed 90%, the specificity ranges between 53-100%. HYPOTHESIS: The study was undertaken to assess characteristics of patients with abnormal stress technetium Tc99m sestamibi SPECT (MIBI) studies without significant coronary artery diameter stenoses (< 50%). METHODS: Between January 1999 and November 2000, 270 consecutive patients were referred for coronary angiography due to reversible MIBI uptake defects during exercise. In 41 patients (15%; 39% women, mean age 59 +/- 9 years), reversible MIBI uptake defects were assessed although coronary angiography showed no significant CAD. These patients were compared with age- and gender-matched patients with perfusion abnormalities (39% women, mean age 60 +/- 9 years), due to significant CAD (coronary artery stenosis > 50%). RESULTS: There were no significant differences between the two groups regarding body mass index, left bundle-branch block (LBBB), or method of stress test (dipyridamole in patients with LBBB or physical inactivity [n = 11] and exercise in all the others [n = 30]). Left ventricular hypertrophy (44 vs. 23%, p = 0.05) and left anterior fascicular block (LAFB) (17 vs. 0%, p = 0.005) were more common in patients with perfusion abnormalities with no significant CAD, whereas ST-segment depression during exercise (17 vs. 37% p = 0.05) and angina during exercise (15 vs. 29%, p = 0.02) were significantly less common than in patients with abnormal MIBI perfusion studies and angiographically significant CAD. Sestamibi uptake defects during exercise were significantly smaller in patients without significant CAD than in matched controls with significant CAD (p < 0.0004). CONCLUSION: Of 270 consecutive patients, 41 (15%) referred to coronary angiography due to reversible MIBI uptake defects showed coronary artery stenoses < 50%. Twenty-six (10%) of these presented angiographically normal coronary arteries. The significantly higher proportion of left ventricular hypertrophy and LAFB in patients with reversible MIBI uptake defects without significant CAD suggest microvascular disease, angiographically underestimated CAD, and conduction abnormalities as underlying mechanisms.     

Measurements of buccal tissue volumes at single-implant restorations after local bone grafting in maxillas: a 3-year clinical prospective study case series

Purpose: The purpose of this study was to measure changes in buccal and proximal tissue volumes after local bone grafting and single‐implant treatment. Materials and Methods: Ten patients were provided with buccal bone grafts 6 months prior to implant treatment in central upper incisor regions. Following a healing time of 6 months, abutments and single‐implant crowns were installed and followed up for 2 years. Clinical photographs and impressions were taken prior to the surgical intervention as well as after crown placement and at first and second annual checkups. The photographs and study models were analyzed with regard to papilla regeneration and changes in buccal crest volume during the study period by means of a clinical papilla index and optical scanning of study models. Results: All bone grafts healed without problems. A significant reduction of the buccal crest volume (‐50%, p <.01) was observed in the grafted area before abutment connection. However, a significant increase of tissue volume (+100%, p <.05) was noticed at the subsequent crown placement, followed by a second but slow reduction of the volume during the following 2 years of function. The interdental papillae increased significantly (p <.05) in volume during the first year, almost completely filling up the embrasure areas after 2 years. Conclusions: It may be concluded that local bone grafting seems to be a valuable protocol to create sufficient bone volume for implant placement. However, significant resorption of the graft may be present, which reduces the impact of grafting on the esthetic outcome. Instead, placement of the abutment cylinder and the crown seems to play a more important role for reestablishing the tissue volume at the implant‐supported single crowns.     

Decrement in area of muscle responses to repetitive nerve stimulation

Measurement of the decremental muscle response to repetitive nerve stimulation (RNS) has low yields for the diagnosis of neuromuscular transmission defects compared with single fiber electromyography (SFEMG). We compared area and amplitude of muscle responses to RNS in 87 patients and 30 controls, using SFEMG as the reference standard. Decrement of response area provided additional diagnostic yields of 5.3% to 30% depending on the muscle examined and disease severity, and is recommended as a diagnostic adjunct to measurement of amplitude decrement during RNS.     

The HOXA1 A218G polymorphism and autism: lack of association in white and black patients from the South Carolina Autism Project

A recent study has suggested that the A218G polymorphism in the homeobox Al (HOXA1) gene may influence susceptibility to autism. We have determined the frequencies of the A and G alleles of the HOXA1 A218G polymorphism in both white and black patients from the South Carolina Autism Project (SCAP) and controls. Marked differences were found in allele frequencies between the races, but no deviations from Hardy-Weinberg equilibrium were seen in either white or black SCAP family members. More direct tests, comparing genotype frequencies between probands and controls and tracking transmission of the A versus G alleles to affected offspring, did not support the contention that allele status for the HOXA1 A218G polymorphism influences one's susceptibility to autism.