Analysis of copy number variation in men with non-obstructive azoospermia.

BACKGROUND: Recent findings demonstrate that single nucleotide variants can cause non-obstructive azoospermia (NOA). In contrast, copy number variants (CNVs) were only analysed in few studies in infertile men. Some have reported a higher prevalence of CNVs in infertile versus fertile men. OBJECTIVES: This study aimed to elucidate if CNVs are associated with NOA. MATERIALS AND METHODS: We performed array-based comparative genomic hybridisation (aCGH) in 37 men with meiotic arrest, 194 men with Sertoli cell-only phenotype, and 21 control men. We filtered our data for deletions affecting genes and prioritised the affected genes according to the literature search. Prevalence of CNVs was compared between all groups. Exome data of 2,030 men were screened to detect further genetic variants in prioritised genes. Modelling was performed for the protein encoded by the novel candidate gene TEKT5 and we stained for TEKT5 in human testicular tissue. RESULTS: We determined the cause of infertility in two individuals with homozygous deletions of SYCE1 and in one individual with a heterozygous deletion of SYCE1 combined with a likely pathogenic missense variant on the second allele. We detected heterozygous deletions affecting MLH3, EIF2B2, SLX4, CLPP and TEKT5, in one subject each. CNVs were not detected more frequently in infertile men compared with controls. DISCUSSION: While SYCE1 and MLH3 encode known meiosis-specific proteins, much less is known about the proteins encoded by the other identified candidate genes, warranting further analyses. We were able to identify the cause of infertility in one out of the 231 infertile men by aCGH and in two men by using exome sequencing data. CONCLUSION: As aCGH and exome sequencing are both expensive methods, combining both in a clinical routine is not an effective strategy. Instead, using CNV calling from exome data has recently become more precise, potentially making aCGH dispensable.

Ulnar neuropathy as a complication of macular hole surgery.

OBJECTIVE: To report a series of patients manifesting ulnar neuropathy as an extraocular complication following macular hole surgery and facedown positioning. METHODS: Retrospective chart review of 7 patients identified by the operating surgeon as developing ulnar neuropathy during the immediate postoperative period after undergoing vitrectomy surgery with fluid-gas exchange for macular hole followed by at least 1 week of strict facedown positioning. RESULTS: All 7 patients developed symptoms of ulnar neuropathy, including paresthesias, dysesthesias, pain, weakness, and muscle atrophy. Signs included abnormal electromyogram, prolonged nerve conduction velocities, and impaired neurologic clinical test results in patients examined. Symptoms did not resolve with cessation of facedown positioning, and with follow-up ranging from 3 to 24 months all patients had persistent symptoms. All patients had positioned themselves with their arms continuously flexed. Three of 7 patients had placed pressure directly on their bent elbows. CONCLUSIONS: Ulnar neuropathy is an extraocular complication of macular hole surgery that can be attributed to arm position during postoperative facedown positioning. Surgeons performing macular hole surgery should caution their patients to minimize the amount of time spent with their elbows in a flexed position. Particular effort should be made to minimize pressure on the bent elbow.

Supporting the home care client receiving chemotherapy.

Chemotherapy has been one of the four major cancer treatment modes for several decades; the other three are surgery, radiation, and immunotherapy. This article presents breast cancer as a model for understanding chemotherapy because, given its prevalence in American populations, the home care provider is highly likely to encounter clients with this diagnosis. Detailed explanations of the categories and pharmacodynamics of cytotoxic drugs are beyond the scope of this article. As always, caregivers should study specific drugs when individual clients are taking them. However, because most cancer patients receive a combination of chemotherapeutic agents and many agents are indicated for a variety of primary tumors, similarities exist in the toxicities clients experience and the appropriate management strategies.

Endogenous Ochrobactrum anthropi endophthalmitis.

PURPOSE: To describe bilateral endogenous endophthalmitis caused by Ochrobactrum anthropi in a partially immunosuppressed patient who had undergone central venous access for hyperalimentation and home intravenous therapy. METHODS: Case report. RESULTS: Blood cultures were positive for O anthropi. Vitreous cultures grew a gram-variable bacillus. The patient's ocular and systemic condition markedly improved after intravitreal antibiotics and systemic ciprofloxacin. CONCLUSIONS: Ochrobactrum anthropi may cause endogenous endophthalmitis in patients with a history of indwelling catheters for venous access or other permanent medical devices.

Late complications following total-body irradiation and bone marrow rescue in mice: predominance of glomerular nephropathy and hemolytic anemia.

Late mortality and pathology were assessed in various mouse strains following total-body irradiation (TBI) and bone marrow transplantation. A, C57BL/6, B6AF1, LP and C3H mice received TBI in two fractions 3 h apart at total doses of between 11 and 15 Gy. They were then transplanted with syngeneic bone marrow cells providing sufficient reconstitution to avoid hemopoietic failure. Long-term survival data revealed both radiation dose- and strain-dependent onset of mortality between 1 and 2 years post-treatment. Renal damage appeared to have contributed to the late mortality in most treatment groups as shown by glomerular lesions, elevated blood urea nitrogen and an accompanying fall in hematocrit. Hemolysis was deduced to be the major cause of anemia, as concluded from results of 51Cr-labeled erythrocyte survival. No decrease in erythropoiesis was evident as seen from spleen and bone marrow 59Fe uptake. These findings are together consistent with the manifestation of a hemolytic uremic syndrome (HUS) with kidney glomeruli representing the principal sites of injury responsible for both renal dysfunction and microangiopathic hemolysis.

Late tissue-specific toxicity of total body irradiation and busulfan in a murine bone marrow transplant model.

Total body irradiation (TBI) and busulfan were compared for late effects in a murine model of bone marrow transplantation (BMT). Male C57BL/6 mice were given fractionated TBI or busulfan given in 4 equal daily doses followed by infusion of 10(7) syngeneic bone marrow cells. Total doses of 16.4 Gy TBI and 3.4 mg busulfan were chosen for their equivalence in inducing near complete engraftment of allogeneic marrow from donor mice of the LP strain. The two treatment groups had a late wave of mortality starting at about 80 weeks after transplantation. Specific tissue damage was manifested in bone marrow stem cells, splenic T-cell precursors, hair greying and cataract formation for both TBI and busulfan but to varying degrees. Severe nephrotoxicity and anemia were observed only after TBI. Although both busulfan and TBI kill early marrow stem cells and are effective preparative agents in bone marrow transplantation, their effects on other stem cell and organ systems are not similar. In addition, many of the injuries seen are late to occur. The delayed expression of injury deserves careful long-term evaluation of BMT recipients before the therapeutic potential of effective preparative regimens can be fully appreciated.

Behavioral interaction in social-deprivation-reared Macaca mulatta: effects of cerebellar lesions on aggressive and afiliative behaviors.

Maintaining isolation-reared adult female Macaca mulatta in a group enclosure resulted in rapid resocialization. The influence of cerebellar lesions on social behaviors was most marked on aggressive interactions and cage stereotype pacing and circling.

Unilateral forelimb deafferentation in the monkey: purposive movement.

Monkeys with unilateral dorsal rhizotomy C2-T3 used their denervated limbs to retrieve unseen food pellets when movements of the intact contralateral limb were rendered ineffective by enclosure of the hand within a container. Even after protracted use in this condition, however, the deafferented limb ceased to be used in the test situation when the intact arm was released. These findings cast doubt on interpretations of lack of use of a unilaterally dorsal rhizotomized limb as being due to cross-spinal inhibition or to learned disuse.