A computerized audit of a screening programme to establish rubella immunity

This paper reports the use of a practice computer to help establish rubella immunity in all women that are likely to bear children. The rubella status by serological testing for each woman in the practice together with the date of the test is entered in the computer by ancillary staff as soon as results are obtained. The computer audit can be carried out by practice staff and takes half an hour. The resulting print-out gives details of rubella immunity for all women aged 14—39 years and also for all women at the beginning of pregnancy. Results of successive audits show consistent increases in the numbers of women with established rubella immunity.     

Immunology: Repeat trials of oocyte donation to women with previous donor oocyte success

Oocyte donation has proven to be highly successful in establishingpregnancy in functionally agonadal women. Both implantationand ongoing pregnancy rates in women using this method havesurpassed those normally seen in standard in-vitro fertilization(IVF) patients. Over a 5 year period, seven women who had previouslyconceived using oocyte donation elected to attempt pregnancyand deliver a second child using the same donor. In each casethe paramount consideration was to provide a sibling of thesame genetic make-up as the child or children previously borne.Of the seven women studied, whose ages ranged from 24 to 44years, five became pregnant on subsequent cycles. The time toconception varied from one to a maximum of three attempts withthree of the five women becoming pregnant on the first cycleand two requiring three cycles to establish the subsequent pregnancy.The overall rate of success in this group was 12 pregnanciesin 20 cycles of embryo transfer (60%). An exaggerated implantationrate (25.6%) was also noted (23 individual embryo implantationsfrom 90 embryos transferred). Of the 12 pregnancies establishedin these seven women, four (33%) were multiple gestations (threetriplets, one twin). We conclude that women who have previouslyexperienced pregnancy following oocyte donation are highly likelyto conceive in a subsequent trial at a rate that may be higherthan that normally seen in the general population of women undergoingoocyte donation.     

HPA-1, 3, 5 genotyping to establish a typed platelet donor panel

Platelet antigen typing of blood donors is not routinely performed. Usually, ABO-matched platelets are transfused. In situations where the recipient has a human platelet-associated (HPA) antibody resulting in refractoriness to platelet transfusions, post-transfusion purpura or neonatal alloimmune thrombocytopenia, HPA-typed platelets may be required. Having a panel of HPA-typed donors would be helpful. This study utilised PCR-RFLP and PCR-SSP methods to determine the HPA-1, 3, 5 genotypes of 1,000 blood donors to establish a panel of HPA homozygous donors who could donate platelets for patients with anti-HPA-antibodies. The study demonstrates the HPA genotype frequencies in a Western Australian blood donor population and has identified donors who are homozygous for the "aa" and "bb" genotypes for HPA-1, 3 and 5. The Australian Red Cross Blood Service-NW Region can now use these data to develop a panel of HPA-1, 3 and 5 "aa" and "bb" homozygous platelet donors, which can be accessed for patients with HPA antibodies requiring platelet transfusion.     

Developing policies and procedures for a picture archiving and communication system

Policies and procedures (P&P) constitute the mechanism for planning, standardizing, and documenting the provision of clinical services. Upon approval by hospital management, the P&P is an official statement of hospital rules and regulations. Each P&P establishes organizational responsibility for providing services. P&P are a mechanism for communicating standard operating procedures to hospital and medical staff. P&P serve as a reference document for unusual events, as well as routine procedures. P&P are often reviewed by inspection teams from the Joint Commission on Accreditation of Hospital Organizations (JCAHO) to determine whether the hospital has documented systematic practices. A picture archival and communications system (PACS) provides a new vehicle for providing radiology services. P&P that were designed for conventional film-based imaging are often not appropriate for electronic imaging. Because PACS is new and not yet widespread, good examples of PACS P&P are not yet available. JCAHO has no official requirements for PACS: PACS is viewed only as a means for the hospital to accomplish its work. Successful P&P development is a team effort, drafted by personnel responsible for executing the procedure, assisted by staff proficient in PACS technology, and tested in the field. The P&P should be reviewed and approved by management personnel knowledgeable about hospital and imaging operations. P&P should be written in clear and concise language. Successful P&P development is an ongoing effort. P&P must be periodically reviewed and updated to reflect changes in PACS technology and changes in clinical operations. New P&P must be developed when a deficit is noted. PACS security is a good example of a topic worthy of P&P development, especially in the face of the Health Insurance Portability and Accountability Act (HIPAA) legislation of 1996. What are the provisions for access control? Does the system include a feature for automatic shut-off of the software? Are there “generic” passwords and log-ins shared by a community of users? How are passwords assigned and how frequently are they changed? What security measures are in place to assure passwords are given to the appropriate user? Who grants and denies access? Service calls are another topic for P&P. Who initiates a service call? What is the process for escalating a service call from the operator level to the vendor? What immediate actions are expected by the operator in order to restore PACS services? How are service events documented? Who is responsible for determining when “downtime” procedures should be initiated or suspended? When our hospital’s total electrical system had to be shut down for an extended period, we found that a P&P was lacking for a task as mundane as shutting down and restarting our PACS components. What is the sequence for the shutdown? Who is responsible for shutting down and restarting? How long can the devices operate on uninteruptible power supplies (UPS)? What components are on emergency power? Should we expect the components to survive the switchover to generator power? Developing this P&P was worth the effort: it made the PACS more fault-tolerant and served as a reference document 3 years later when expansion of our physical plant required two more power outages.     

Portion of a nerve trunk can be used as a donor nerve to reconstruct the injured nerve and donor site simultaneously

This study aims to estimate the effects of using a portion of a nerve trunk to repair itself and the injured nerve simultaneously. Proximal 1/2 median nerve served as donor nerve to repair the distal 1/2 median and whole ulnar nerve. Four months postoperation, the number of myelinated axons and nerve conduction velocities of the distal half median and ulnar nerve were (2033 ± 135 and 24.6 ± 5.3 m/s) and (1138 ± 228 and 30.3 ± 7.2 m/s). It suggests that using a portion of a nearby nerve truck to reconstruct itself and the injured nerve simultaneously is a practical method for severe peripheral nerve injury.     

Phenylketonuria screening registry as a resource for population genetic studies

Background: Neonatal screening for metabolic diseases, involving samples stored on filter paper (Guthrie spots), provides a potential resource for genetic epidemiological studies. Objective: To develop a method to make these dried blood spots available for large scale genetic epidemiology. Methods: DNA from untraceable Guthrie spots was extracted using a saponin and chelex-100 based method and preamplified by improved primer preamplification. Analyses were done on 38 samples each of fresh, 10, and 25 year old Guthrie spots and the success rate determined for PCR amplification for five amplicon lengths. Results: The method was applicable even on 25 year old samples. The success rate was 100% for 100 bp amplicons and 80% for 396 bp amplicons. Ninety four Guthrie samples were genotyped, including carriers of two different PKU mutations; all carriers were found (six R158Q, four R252W), with no false positives. Finally, 2132 anonymous samples from the Swedish PKU registry were extracted and preamplified and the allele frequencies of APOε4, PPARγ Pro12Ala, and the CCR5 32 bp deletion determined. Local variations in allele frequencies suggested subpopulation structuring. There was a significant difference (p<0.01) in regional allele frequencies for the CCR5 32 bp deletion in the Swedish population. Conclusion: Whole genome amplification makes it feasible to conduct large genetic epidemiological studies using PKU screening registries.     

Diagnostic strategy used to establish etiologies of encephalitis in a prospective cohort of patients in England

The laboratory diagnostic strategy used to determine the etiology of encephalitis in 203 patients is reported. An etiological diagnosis was made by first-line laboratory testing for 111 (55%) patients. Subsequent testing, based on individual case reviews, resulted in 17 (8%) further diagnoses, of which 12 (71%) were immune-mediated and 5 (29%) were due to infection. Seventy-five cases were of unknown etiology. Sixteen (8%) of 203 samples were found to be associated with either N-methyl-d-aspartate receptor or voltage-gated potassium channel complex antibodies. The most common viral causes identified were herpes simplex virus (HSV) (19%) and varicella-zoster virus (5%), while the most important bacterial cause was Mycobacterium tuberculosis (5%). The diagnostic value of testing cerebrospinal fluid (CSF) for antibody was assessed using 139 samples from 99 patients, and antibody was detected in 46 samples from 37 patients. Samples collected at 14 to 28 days were more likely to be positive than samples taken 0 to 6 days postadmission. Three PCR-negative HSV cases were diagnosed by the presence of virus-specific antibody in the central nervous system (CNS). It was not possible to make an etiological diagnosis for one-third of the cases; these were therefore considered to be due to unknown causes. Delayed sampling did not contribute to these cases. Twenty percent of the patients with infections with an unknown etiology showed evidence of localized immune activation within the CNS, but no novel viral DNA or RNA sequences were found. We conclude that a good standard of clinical investigation and thorough first-line laboratory testing allows the diagnosis of most cases of infectious encephalitis; testing for CSF antibodies allows further cases to be diagnosed. It is important that testing for immune-mediated causes also be included in a diagnostic algorithm.     

A BALB/c murine lung alveolar carcinoma used to establish a surgical spontaneous metastasis model

Line-1, a weakly immunogenic lung tumor cell line derived from the BALB/c mouse, metastasizes spontaneously to the lungs of mice following subcutaneous administration. The parameters that influence metastasis as well as the progression of metastatic lung disease following surgical resection of primary subcutaneous tumors were characterized. Histological analysis of the lungs obtained from mice bearing different size subcutaneous tumors demonstrated that >90% of the mice developed micrometastatic disease in the lungs when the tumor exceeded 650 mm3 in size. Surgical resection of subcutaneous tumors resulted in the cure of primary disease in 95% of the mice. Macroscopic tumor nodules were grossly visible in the lungs of 75% of the mice 5 weeks after surgery. Serum amyloid A level correlated with primary tumor burden and was diagnostic for the presence of metastatic disease. The efficiency of metastasis, post-surgical primary tumor recurrence and long-term survival were significantly different between BALB/c mice obtained from different suppliers. The Line-1-BALB/c surgical metastasis model provides a clinically relevant tool for the evaluation of anti-cancer therapies, especially those that are designed to target long-term suppression of minimal residual disease following surgical intervention.     

Description of fourteen new DRB alleles found in a stem cell donor registry

Fourteen DRB alleles, DRB1*0705, DRB1*11014, DRB1*1134, DRB1*1136, DRB1*1141, DRB1*1335, DRB1*1337, DRB1*1338, DRB1*1342, DRB1*1343, DRB1*1349, DRB1*1510, DRB3*0105, and DRB5*0103, are described. Among them, eleven are variants which differ by only one nucleotide from previously described alleles, including one silent variant (DRB1*11014). Alleles, DRB1*0705, DRB1*1335 and DRB3*0105, display unique sequence motifs that have never been observed in DRB alleles.     

Conscious sedation and analgesia for oocyte retrieval during IVF procedures: a Cochrane review

BACKGROUND: Various methods of sedation and analgesia have been used for pain relief during oocyte recovery during IVF. OBJECTIVE: To compare conscious sedation and analgesia with alternative methods for pain relief and pregnancy outcomes. METHODS: We searched the Specialised Register of the Menstrual Disorders and Subfertility Group, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, the National Research Register and Current Controlled Trials up to February 2004. RESULTS: Twelve trials were included. Owing to considerable heterogeneity, regarding types and dosages of sedation or analgesia used, and tools used to assess pain, a meta-analysis was attempted only in trials where appropriate data were available. Clinical pregnancy rates per woman in individual trials were comparable. Data on pain showed conflicting results. CONCLUSION: No single method or delivery system appeared superior for pregnancy rates and pain relief. Future studies need to be consistent in the choice of tools used to measure pain and the timing of such evaluations.     

Approaches to managing volunteer marrow donor registry HLA data. Algorithms for directing donor center-initiated HLA-DR typing of selected donors

The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations     

Uro-retroperitoneum after ultrasound-guided transvaginal follicle puncture in an oocyte donor: a case report

Ultrasound-guided transvaginal follicle aspiration is the standard technique for oocyte retrieval prior to IVF. Complications are rare, but some are potentially serious. We report a case of ureteral injury with acute-onset uro-retroperitoneum in a volunteer oocyte donor. The patient recovered rapidly after ureteral stenting. This case underlines the need for all candidate oocyte donors to receive proper information on serious procedure-related complications.     

Psychological screening and the success of donor insemination

In a previous case series, a psychologist‘s rating ofcouples’ emotional adjustment and readiness for donorinsemination was predictive of pregnancy rates. We attemptedto replicate this finding with an extended series of 120 consecutivecouples in which each spouse filled out questionnaires whenevaluated for donor insemination. The Stress and InfertilityQuestionnaire measured specific attitudes and anxieties aboutdonor insemination. The Brief Symptom Inventory assessed psychologicaldistress. The Dyadic Adjustment Scale measured marital happiness.A psychologist used these questionnaires to rate the couple‘soverall adjustment in regard to donor insemination. Those couplesrated as distressed had a session of psychological counselling.Outcome was reviewed at a mean of 20 months after evaluation,with categories of pregnancy, continuing donor insemination,failure to begin the programme, or dropped out. For the 120couples overall, psychological factors did not predict pregnancyoutcome. Younger age of the wife did predict higher pregnancyrates     

Determining optimal screening policies using decision trees and spreadsheets

The determination of the proportion of population to be screened, so that overall costs are minimized, is treated. A decision tree approach is used, based on knowing the probabilities and costs of all possible outcomes. This involves specifying models that estimate the prevalences in the screened and non-screened groups for various screening levels. The generalized implementation on a microcomputer spreadsheet that is presented permits sensitivity and optimality to be explored for different parameter conditions. A numerical example illustrates the results.     

Sequence of a novel HLA-A2 allele in a haematopoietic stem cell donor of the international registry

We report here the sequence of a new human leucocyte antigen-A2 allele, A*9251, identified in a volunteer haematopoietic stem cell donor of the international registry. A*9251 differs from A*02010101 by two nucleotides at codons 113–114, resulting in a single His>Asp substitution at codon 114.     

Fallopian tube sperm perfusion used in a donor insemination programme.

Ninety-six couples were enrolled in a programme of Fallopian tube sperm perfusion (FSP). FSP is a method combining ovarian stimulation, ovulation induction and intra-uterine insemination with a 4 ml volume of sperm suspension. Frozen/thawed donor semen was used in all cycles. A total of 196 treatment cycles were started and of these 172 were completed. Twenty cycles were cancelled because of maturation of too many follicles, a low ovarian response, or formation of ovarian cysts. Five of the women enrolled in the programme did not have any inseminations. Forty-eight pregnancies occurred (27.9% per cycle) among 45 women (49.5%). There were five spontaneous abortions and one ectopic pregnancy. Sixteen pregnancies are on-going (greater than 12 weeks) and 26 women have delivered (including two sets of triplets and one set of twins). The pregnancy rate declined from the first attempt (34.1%) to the fourth attempt (14.3%). The pregnancy rate was significantly higher in women with three to five mature follicles compared to women with two or fewer mature follicles (P less than 0.05). Cycles in which human chorionic gonadotrophin (HCG) was administered on day 11 or later had a higher pregnancy rate than cycles where HCG was administered on day 10 (P less than 0.01). There was no difference in pregnancy rates between insemination with 8-10 x 10(6) motile spermatozoa and insemination with greater than 30 x 10(6) motile spermatozoa. FSP used in a programme of artificial insemination by donor using frozen/thawed donor semen is relatively simple to perform and gives a high pregnancy rate per cycle.     

CASE REPORT: Continuation of a donor oocyte pregnancy in a functionally agonadal patient without early oestrogen support

A 40 year old functionally agonadal patient was the recipientof fertilized donated oocytes. She accidentally discontinuedall oestrogen support on the day preceding embryo transfer untilit was reinstated 12 days later. However, a pregnancy was establishedand resulted in the birth of healthy normal twin infants. Thiscase report suggests that minimal amounts, if any, of oestradiolare sufficient to maintain an early pregnancy, provided adequateamounts of progesterone are given. This is consistent with arecent study conducted in subhuman primates.