Effects of androgenic gland ablation on male primary and secondary sexual characteristics in the Malaysian prawn, Macrobrachium rosenbergii (de Man) (Decapoda,Palaemonidae), with first evidence of induced feminization in a nonhermaphroditic decapod

Male Macrobachium rosenbergii (de Man), categorized into three developmental stages according to possession of male gonopore complexes, appendixes masculina, and mature chelipeds, were subjected to bilateral androgenic gland ablation (andrectomy). Andrectomized males initially lacking appendixes masculina and mature chelipeds do not develop them; those initially possessing appendixes masculina and mature chelipeds do not lose them. Growth rate of the appendixes masculina, however, is reduced. Andrectomized males are unable to redifferentiate amputated or accidentally lost appendixes masculina and mature chelipeds. Instead, the appendages regenerate as immature forms. Andrectomized M. rosenbergii possess atrophied testes and vasa deferentia. Histological sections of the testes revealed a reduction in number of spermatogenic lobules. Spermatogonia and primary spermatocytes were commonly found; secondary spermatocytes and spermatids were found only occasionally. Andrectomy appears to inhibit but not prevent meiosis. Feminization occurred in five andrectomized males. Complete feminization, including initiation of oogenesis and development of oviducts and female gonopores, occurred in males andrectomized in the youngest developmental stage. Males andrectomized in later developmental stages were either partially feminized or not feminized. Reimplantation of androgenic glands reverses the effects of andrectomy. Remasculinization, as evidenced by differentiation of appendixes masculina, was noted after the first postimplantation molt. The testes of remasculinized males were normal in gross anatomy and spermatogenic ability. The data indicate a uniform function for the androgenic glands with respect to male primary and secondary sexual characteristics among the Amphipoda, Isopoda, and Decapoda. Past theories on androgenic gland function are modified in light of the present information.     

Safety and tolerability of linaclotide for the treatment of chronic idiopathic constipation and irritable bowel syndrome with constipation: pooled Phase 3 analysis

Background: Linaclotide is approved for treating irritable bowel syndrome with constipation (IBS-C; 290 µg QD) and chronic idiopathic constipation (CIC; 145 µg or 72 µg QD). These analyses aimed to assess linaclotide safety in a large, pooled Phase 3 population.

Methods: In six randomized controlled trials (RCTs), patients received linaclotide (72 µg, 145 µg, 290 µg) or placebo daily for 12–26 weeks; in two long-term safety (LTS) studies, patients received open-label linaclotide for ≤78 additional weeks. Laboratory values, vital signs, and treatment-emergent adverse events (TEAEs) were assessed.

Results: Overall, 3853 patients received ≥1 dose of linaclotide. The most common TEAE was diarrhea (majority [90.5% in RCTs] mild/moderate). Linaclotide patients experienced 1.1 diarrhea TEAE per patient-year in the RCTs (0.2 in placebo), and 0.3 in the LTS studies. In RCTs, 6.9% linaclotide and 3.0% placebo patients discontinued due to any adverse event (AE); 4.0% linaclotide and 0.3% placebo patients discontinued due to diarrhea. In LTS studies, 9.4% patients discontinued due to any AE, and 3.8% due to diarrhea. Serious AEs (SAEs) were rare and similar across treatment groups; there were no SAEs of diarrhea.

Conclusion: These pooled analyses of patients treated for ≤104 weeks confirm linaclotide’s overall safety.     

Left ventricular hypertrophy is a common echocardiographic abnormality in severe obstructive sleep apnea and reverses with nasal continuous positive airway pressure

STUDY OBJECTIVES: To determine cardiac structural abnormalities by echocardiography in subjects with severe obstructive sleep apnea (OSA), and to determine the long-term effects of nasal continuous positive airway pressure (CPAP) on such abnormalities. DESIGN: Polysomnography was conducted on oximetry-screened patients who showed a desaturation index > 40/h and > or = 20% cumulative time spent below 90%. From these, 25 patients with severe OSA but without daytime hypoxemia underwent echocardiography prior to, then 1 month and 6 months following initiation of CPAP treatment. SETTING: Outpatient sleep disorders center. RESULTS: Of the 25 patients, 13 patients (52%) had hypertension by history or on physical examination. Baseline echocardiograms showed that severe OSA was associated with numerous cardiovascular abnormalities, including left ventricular hypertrophy (LVH) [88%], left atrial enlargement (LAE) [64%], right atrial enlargement (RAE) [48%], and right ventricular hypertrophy (16%). In all patients (intent to treat) as well as those patients compliant with CPAP therapy (84% > 3 h nightly), there was a significant reduction in LVH after 6 months of CPAP therapy as measured by interventricular septal distance (baseline diastolic mean, 13.0 mm; 6-month mean after CPAP, 12.3 mm; p < 0.02). RAE and LAE were unchanged after CPAP therapy. CONCLUSIONS: LVH was present in high frequency in subjects with severe OSA and regressed after 6 months of nasal CPAP therapy.     

The presence of an intrahepatic cytotoxic T lymphocyte response is associated with low viral load in patients with chronic hepatitis C virus infection

BACKGROUND/AIMS: The role of cytotoxic T lymphocytes (CTL) in limiting viral replication and producing hepatocellular injury in patients with chronic hepatitis C virus (HCV) infection is controversial. METHODS: Intrahepatic and peripheral blood HCV-specific CTL activity against the entire HCV polyprotein was assessed in 26 patients. CTL responses were assessed after effector lymphocytes were re-stimulated for 6 days in vitro using HCV-vaccinia virus-infected autologous cells expressing HCV antigens. Serum and hepatic viral loads were measured and immunohistochemistry for CD3 and CD8 was performed to localise and enumerate effector cells in liver. RESULTS: A positive CTL response was detected in 39/52 (75%) of assays conducted with intrahepatic mononuclear cells and 21/52 (40%) of peripheral blood assays (P<0.001). The presence of an intrahepatic CTL response was associated with low hepatic viral load (P=0.004). Hepatic lobular infiltration by CD8(+)T cells correlated weakly with serum alanine aminotransferase levels (r=0.42, P=0.04) and no relationship was demonstrated between CTL activity and histological evidence of liver damage. CONCLUSIONS: HCV-specific CTL activity is found more commonly in liver than in blood. An inverse relationship between CTL responses and viral load supports the hypothesis that HCV-specific CTL limit viral replication in patients with chronic HCV infection.     

The time course of metonymic language text processing by older and younger adults

The influence of aging on the processing of figurative language was investigated by utilizing Frisson and Pickering's (Journal of Experimental Psychology: Learning, Memory, and Cognition, 25, 1366-1383, 1999) paradigm, monitoring eye fixation times to target words in sentences. First fixation times and total fixation times were analyzed for familiar and unfamiliar metonymies and literal control sentences. Frisson and Pickering found that processing figurative and literal expressions yielded similar patterns of eye fixations. In the current study, these methods and results were replicated and extended to include older adults' processing of metonymies. This investigation replicated their findings for young adults and found that older adults produced the same processing patterns as the younger adults.     

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.     

Vaginal Delivery After Ileal Pouch-Anal Anastomosis: A Word of Caution

PURPOSE This study was designed to evaluate the impact of childbirth on anal sphincter integrity and function, functional outcome, and quality of life in females with restorative proctocolectomy and ileal pouch-anal anastomosis.METHODS The patients who had at least one live birth after ileal pouch-anal anastomosis were asked to return for a comprehensive assessment. They were asked to complete the following questionnaires: the Short Form-36, Cleveland Global Quality of Life scale, American Society of Colorectal Surgeons fecal incontinence severity index, and time trade-off method. Additionally, anal sphincter integrity (endosonography) and manometric pressures were measured by a medical physician blinded to the delivery technique. Anal sphincter physiology also was evaluated with electromyography and pudendal nerve function by nerve terminal motor latency technique.RESULTS Of 110 eligible females who had at least one live birth after ileal pouch-anal anastomosis, 57 participated in the study by returning for clinical evaluation to the clinic and 25 others by returning the quality of life and functional outcome questionnaires. Patients were classified into two groups: patients who had only cesarean section delivery after ileal pouch-anal anastomosis (n = 62) and patients who had at least one vaginal delivery after ileal pouch-anal anastomosis (n = 20). The mean follow-up from the date of the most recent delivery was 4.9 years. The vaginal delivery group had significantly higher incidence of an anterior sphincter defect by anal endosonography (50 percent) vs. cesarean section delivery group (13 percent; P = 0.012). The mean squeeze anal pressure was significantly higher in the patients who had only cesarean section delivery (150 mmHg) after restorative proctocolectomy than patients who had at least one vaginal delivery (120 mmHg) after restorative proctocolectomy (P = 0.049). Quality of life evaluated by time trade-off method also was significantly better in the cesarean section delivery group (1) vs. vaginal delivery group (0.9; P < 0.001).CONCLUSIONS The risk of the sphincter injury and quality of life measured by time trade-off method are significantly worse after vaginal delivery compared with cesarean section in patients with ileal pouch-anal anastomosis. In the short-term, this does not seem to substantially influence pouch function or quality of life; however, the long-term effects remain unknown, thus obstetric concern may not be the only factor dictating the type of delivery in this group of patients. A planned cesarean section may eliminate these potential and factual concerns in ileal pouch-anal anastomosis patients.Podium presentation at the meeting of The American Society of Colon and Rectal Surgeons, Dallas, Texas, May 8 to 13, 2004.