Alendronate for osteoporosis in men with androgen-repleted hypogonadism

Male hypogonadism is associated with low bone mineral density (BMD) and an increased risk of fractures. Testosterone replacement therapy improves BMD in young hypogonadal men. This effect is milder in older patients, who are at greater risk for fractures. We studied the effects of alendronate or placebo on BMD in 22 osteoporotic men, 29–69 years of age (mean, 50.2±11.2 years) with long-standing hypogonadism, receiving standard testosterone replacement treatment. Alendronate 10 mg daily ( n =11) increased lumbar-spine BMD by 6.0 and 8.4% at 6 and 12 months, respectively, compared with –0.5% at 6 months and +3.3% at 12 months in the placebo group ( n =11; P <0.005). Alendronate also increased mean femoral-neck BMD by 1.9% after 1 year, compared to a 1.4% decrease with placebo ( P <0.005), and increased the total body bone mineral content by 4.4%, compared to a 0.6% decrease with placebo ( P =0.07). After 6 months alendronate suppressed urinary deoxypyridinoline by 50% ( P <0.005), compared to a 24% decrease in the placebo group. Both the alendronate and placebo groups continued with alendronate 70 mg once weekly for the following 2 years. Lumbar-spine BMD during this open-label study phase did not change significantly in the group originally treated with alendronate, but continued to increase in the placebo-alendronate group by 5.4, 6.5, and 6.2% after 18 (6 months of alendronate), 24 and 36 months, respectively ( P <0.05). Femoral-neck BMD continued to increase in both groups receiving active therapy; in the alendronate-alendronate group by 3.7, 2.7, and 5.2% after 18, 24, and 36 months, respectively ( P =0.01), and in the placebo-alendronate group by 0.7 and 1.9% at 24 (first 12 months of alendronate) and 36 months, respectively ( P <0.05). Our results support the long-term administration of alendronate along with testosterone replacement to men with hypogonadism-induced osteoporosis.     

Acidic amino acids evoke a smaller [Ca]i rise in GABAergic than non-GABAergic hippocampal neurons

Changes in intracellular calcium concentration ([Ca²⁺]_i) in response to topical application of the glutamate agonists N-methyl-d-aspartate (NMDA), or amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) were measured in cultured rat hippocampal neurons loaded with Fluo-3 and visualized in a confocal laser scanning microscope. These neurons were subsequently stained for the presence of the enzyme marker for γ-amino butyric acid (GABA), glutamate decarboxylase (GAD). GAD-positive, putative interneurons were less responsive to NMDA and AMPA than GAD-negative neurons. The time course of the rise and decay of [Ca²⁺]_i was similar in the two groups of neurons. Also, there was no clear difference in the shape and size of these two neuron groups indicating that the difference between them is not due to diffusion distances. These data indicate that interneurons are probably more able to handle a calcium load than other neurons, a difference that may underly their resistance to treatments which cause degeneration of other neurons in the hippocampus.     

A case of basal cell carcinoma treated with photodynamic therapy – changes in histological features and bcl-2 expression

Photodynamic therapy (PDT) is based on the phototoxicity of photosensitizers, mostly porphyrins. Since systemic photodynamic therapy with δ-aminolevulinic acid (δ-ALA) causes prolonged whole-skin photosensitivity, topical photodynamic therapy was developed. We describe the histological findings and the results of immunohistochemical staining for bcl-2 protein in the basal cell carcinoma of a 71-year-old patient treated by photodynamic therapy with δ-ALA. After histological confirmation of the diagnosis, 20%δ-ALA in an aqueous cream base was applied to one lesion for 3 h. After 3 h the tumor was exposed to light emitted by a Kodak carousel light projector. Biopsies were taken before exposure and at days 3 and 21 after exposure. The specimens were stained with hematoxylin-eosin and with monoclonal antibody to bcl-2 protein. The intermediate histological response 3 days after exposure was characterized by "squamoid" transformation of the tumor cells along with signs of necrosis, loss of bcl-2 expression and an inflammatory cell reaction. Clinical and histological examinations 3 weeks after treatment showed no sign of residual tumor.     

Stress-induced activation of the hippocampal cholinergic system and the pituitary-adrenocortical axis

The septo-hippocampal cholinergic system in rats undergoes rapid activation after acute stress. This is expressed by rapid increases both in high affinity choline uptake and newly synthesized acetylcholine release. Administration of ACTH or corticosterone at a high dose led 10 min later to changes comparable to those observed after acute stress. Choline uptake and acetylcholine release were also elevated 2 days after adrenalectomy. The effects of adrenalectomy could be attenuated by corticosterone, but not by ACTH treatment. The results demonstrate that (a) after short term stress the septo-hippocampal cholinergic system is activated secondary to activation of the pituitary-adrenocortical axis and (b) major changes in circulating corticosterone can modulate the activity of the hippocampal cholinergic synapse.     

Gastrointestinal carcinomas occurring in breast cancer patients

Breast cancer patients are reported to have a higher rate of second primary malignancies. We retrospectively reviewed the coexistence of breast and gastrointestinal (GI) tumors in the same patients and the characteristics of the tumors. The charts of all patients more than 35 years of age who were diagnosed with breast cancer and hospitalized for various reasons between 1985 and 2003 were reviewed and those who also had a diagnosis of GI malignancy were then selected. Age and tumor characteristics were evaluated. Out of all the patients, 2,650 had a diagnosis of breast cancer, while 40 (1.5%) also had GI malignancies. Among a comparable group of 70,784 consecutive female patients without breast cancer, 1,292 patients (1.8%) had a diagnosis of GI malignancy. The location of GI tumors in patients with both tumors was as follows: stomach, 6 (15%); right colon, 8 (20%); left colon, 7 (17.5%); sigma, 9 (22.5%); and rectum, 10 (25%). Seventeen of the patients (51.5%) had Dukes C and D tumors, 14 (42.5%) Dukes B, and 2 (6%) Dukes A or in situ. The stage of the others was not identified. The mean age at diagnosis of breast cancer was 68.5 years (range 48-88 years). In 23 (57.5%), GI cancer was diagnosed after breast cancer, in 7 (17.5%) it was diagnosed within 3 months of diagnosing breast cancer, and in 8 (20%) it was diagnosed prior to the diagnosis of breast cancer. Five patients suffered from an additional primary cancer: three endometrial, one lung, one esophageal, and one patient had two additional tumors in the endometrium and thyroid. We conclude that the rate of GI malignancies in breast cancer patients is slightly lower than in comparable patients without breast cancer. GI malignancies tend to be diagnosed later and are found more often in the distal colon.     

Polyamine biosynthesis is required for survival of sympathetic neurons after axonal injury

Treatment of adult rats with specific inhibitors of polyamine synthesizing enzymes prevented the early increase in ornithine decar☐ylase activity and polyamine content in the superior cervical ganglion after the postganglionic nerve was cut. Moreover, after axotomy, this treatment led to a marked diminution of the chromatolytic response with a marked neuronal cell death. We conclude that after axonal injury an early increase in polyamine biosynthesis, probably within parent sympathetic neurons, is an obligatory step in the progression of the axon reaction.     

The Jerusalem psychiatric mother-baby unit

Summary The Jerusalem mother and baby unit (MBU) is influenced by the psychoanalytical orientation of the staff, and the historical and cultural conditions surrounding the unit. Forty-three patients with 44 babies (one set of twins) were admitted in 13 years, a rate of admission far from the theoretical demand. Schizophrenia, schizoaffective disorder and mood disorders have been the major diagnoses in more than 50% of the patients.Mothers with schizophrenia were significantly more likely to be admitted sooner after the birth than mothers without schizophrenia (p = 0.025). One infant was separated from the mother on discharge and four recommendations for adoption were given.     

Quality of Evidence to Compare Outcomes of Open and Robot-Assisted Laparoscopic Prostatectomy

Robot-assisted laparoscopic radical prostatectomy (RALP) has gained widespread acceptance in the treatment of prostate cancer. While it increasingly is becoming the surgical approach of choice in many centers, limited data exist directly comparing it to radical retropubic prostatectomy (RRP). This review examines the evidence comparing RALP to RRP. The outcomes evaluated are arranged into perioperative, oncologic, and functional outcomes. Of the 21 publications meeting our selection criteria, Level II, III, and IV evidence were found in 9, 1, and 11 articles, respectively. Overall, RALP was associated with lower blood loss, transfusion rates, length of stay, and higher cost when compared to RRP. Definitive conclusions regarding complications and oncologic and functional outcomes are not yet possible, and will require longer-term follow-up and well-designed randomized controlled trials.     

Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses

Rare sequence variants may be important in understanding the biology of common diseases, but clearly establishing their association with disease is often difficult. Association studies of such variants are becoming increasingly common as large-scale sequence analysis of candidate genes has become feasible. A recent report suggested SLITRK1 (Slit and Trk-like 1) as a candidate gene for Tourette Syndrome (TS). The statistical evidence for this suggestion came from association analyses of a rare 3'-UTR variant, var321, which was observed in two patients but not observed in more than 2000 controls. We genotyped 307 Costa Rican and 515 Ashkenazi individuals (TS probands and their parents) and observed var321 in five independent Ashkenazi parents, two of whom did not transmit this variant to their affected child. Furthermore, we identified var321 in one subject from an Ashkenazi control sample. Our findings do not support the previously reported association and suggest that var321 is overrepresented among Ashkenazi Jews compared with other populations of European origin. The results further suggest that overrepresentation of rare variants in a specific ethnic group may complicate the interpretation of association analyses of such variants, highlighting the particular importance of precisely matching case and control populations for association analyses of rare variants.